FTY720 For Relapsing Multiple Sclerosis - Phase II Data Shows ...
Medical News Today (press release) - UK
... both clinical relapses and inflammatory disease activity are maintained over 18 months," said Dr. Paul O'Connor, MD, St. Michael's Institute, Toronto, Canada. ...

Long-Term Data for Fingolimod Show Significant Efficacy and Safety ...
DG News - USA
... disease activity are maintained over 18 months," said Paul O'Connor, MD, St. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada. Dr. O'Connor ...

Elan gets positive opinion on TYSABRI drug from EMEA science ...
Forbes - USA
... the scientific committee of the European Medicines Agency has issued a positive opinion recommending marketing authorization for its TYSABRI multiple sclerosis ...

ADR Report: Latin America Issues Lead Overall ADR Climb
Yahoo! News - USA
... to $14.70 as the scientific committee of the European Medicines Agency recommended the return to market of its key drug, multiple-sclerosis treatment Tysabri. ...

Recommendations on Tysabri release restriction
RTE.ie - Ireland
The European Medicine's Agency (EMA) has recommended that the multiple sclerosis treatment drug, Tysabri, should be made available to patients on a restricted ...
See all stories on this topic

Stocks Down Following Microsoft Outlook
Forbes - USA
... said the scientific committee of the European Medical Agency issued a positive opinion about recommending marketing authorization for Tysabri, the multiple ...

Woman with MS hopes for relief
LaCrosse Tribune - LaCrosse,WI,USA
... The Holmen, Wis., woman used Tysabri, which was withdrawn in February 2005 after only four months on the market when three people in clinical trials developed ...

More Good News for Tysabri
TheStreet.com - USA
An advisory committee to European drug regulators is recommending that Tysabri, the multiple sclerosis drug from Biogen Idec (BIIB:Nasdaq - commentary ...
See all stories on this topic

http://pharmalive.com/news/index.cfm?articleID=335705&categoryid=47

CAMBRIDGE, Mass. and DUBLIN, Ireland--(BUSINESS WIRE)--Apr 28, 2006 - Biogen Idec (NASDAQ: BIIB) and Elan Corporation, plc (NYSE: ELN) announced today that the Committee for Medicinal Products for Human Use (CHMP), the scientific committee of the European Medicines Agency (EMEA), issued a positive opinion recommending marketing authorization for TYSABRI(R) (natalizumab) as a treatment for relapsing-remitting multiple sclerosis (MS) to delay the progression of disability and reduce the frequency of relapses. The Committee recommended that TYSABRI be used as single disease modifying therapy either in patients with highly active relapsing-remitting MS who have failed to respond to treatment with a beta-interferon, or in patients who have rapidly evolving severe relapsing-remitting MS.

In making its recommendation, the CHMP reviewed available data from the development of TYSABRI, including data from the Phase III AFFIRM monotherapy trial, the Phase III SENTINEL trial in which TYSABRI was added to AVONEX(R) (Interferon beta-1a); and a comprehensive safety analysis, which included the assessments for cases of progressive multifocal leukoencephalopathy (PML). The CHMP also reviewed a Risk Management plan to assess and minimize risks, including PML and other serious opportunistic infections.

The CHMP's positive recommendation for TYSABRI will be considered for final marketing approval by the European Commission. Final approval customarily follows the CHMP's recommendation, which the companies anticipate will be this summer. The European Commission is the final decision-making body for all centrally-reviewed medicinal products that are to be introduced in the EU market.

About Biogen Idec

Biogen Idec creates new standards of care in oncology, neurology and immunology. As a global leader in the development, manufacturing, and commercialization of novel therapies, Biogen Idec transforms scientific discoveries into advances in human healthcare. For product labeling, press releases and additional information about the company, please visit www.biogenidec.com.

About Elan

Elan Corporation, plc is a neuroscience-based biotechnology company committed to making a difference in the lives of patients and their families by dedicating itself to bringing innovations in science to fill significant unmet medical needs that continue to exist around the world. Elan shares trade on the New York, London and Dublin Stock Exchanges. For additional information about the company, please visit www.elan.com.

Safe Harbor/Forward Looking Statements

This press release contains forward-looking statements regarding the potential therapeutic uses and regulatory path forward of TYSABRI. The commercial potential and regulatory path forward of TYSABRI are subject to a number of risks and uncertainties. Factors which could cause actual results to differ materially from the companies' current expectations include the risk that we may unable to adequately address concerns or questions raised by FDA or European regulatory authorities during the regulatory review process, that concerns may arise from additional data or analysis, or that the companies may encounter other unexpected delays or hurdles. There is also no assurance that the companies will be able to resume marketing and sales of TYSABRI. Drug development and commercialization involves a high degree of risk. For more detailed information on the risks and uncertainties associated with the companies' drug development and other activities, see the periodic reports that Biogen Idec and Elan have filed with the Securities and Exchange Commission. The companies assume no obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise.

Contact Media Contacts: Biogen Idec Amy Brockelman, 617-914-6524 or Katja Buller, 41 41 392 1792 or Elan Davia B. Temin, 212-407-5740 or Elizabeth Headon, 353-1-498-0300 or Investor Contacts: Biogen Idec Oscar Velastegui, 617-679-2812 or Elan Emer Reynolds, 353 1 709 4000 or Chris Burns, 800-252-3526

http://www.msleaders.org/ms-leaders/cme/HotAM_main.asp

Sponsored by the Postgraduate Institute for Medicine
Release date: April 2006
Expiration date: April 2007
Estimated time to complete activity: 1 hour

This educational program is supported through an educational grant from Biogen IDEC and Elan Pharmaceuticals Inc.

PROGRAM OVERVIEW
Each year the American Academy of Neurology, at its Annual Meeting, hosts several sessions devoted to highlighting the best research in select neurological topics from more than 1,400 scientific poster and platform presentations. Pertinent abstracts in the multiple sclerosis arena are selected for a session, where expert academicians summarize the most interesting and relevant research presented. Since not all treating MS clinicians can attend the AAN Annual Meeting, MSLeaders has recruited the same two discussants chosen by AAN for their session to provide a recap of the Scientific Highlights for our viewers.


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Biogen Idec Inc. said first-quarter profit almost tripled on lower costs and higher sales of treatments for cancer and multiple sclerosis.

Net income jumped to $123 million, or 36 cents a share, from $43.5 million, or 12 cents, a year earlier when the Cambridge company had costs related to its withdrawal of the multiple sclerosis drug Tysabri. Revenue increased 4 percent to $611.2 million.

Sales of the Avonex MS treatment, introduced in 1996, rose 5 percent to $393 million. US regulators are to decide by the end of June on the return to market of Tysabri.

The company was expected to earn 48 cents a share, based on the average estimate in a Thomson Financial survey of 20 analysts. (Bloomberg)

Financial ties of panels failed to sway decisions

By Diedtra Henderson, Globe Staff | April 26, 2006

WASHINGTON -- A consumer group's study of Food and Drug Administration advisory panel members with financial ties to the drug industry reached a surprising conclusion: They did not dramatically sway the meeting outcomes.

The analysis by Public Citizen, reported in today's Journal of the American Medical Association, looked at 221 meetings held by 16 advisory committees from Jan. 1, 2001, to Dec. 31, 2004. The FDA routinely follows its outside experts' advice when deciding such thorny issues as whether to return the multiple sclerosis treatment Tysabri to the market.

Some 73 percent of the FDA advisory meetings included at least one adviser with financial ties to the drug industry. Nineteen percent of the advisers who were drug company consultants were paid more than $10,000 during the previous year. Nearly one-quarter of drug industry contracts or grants reported by FDA advisers exceeded $100,000. Only 1 percent of the advisers with financial conflicts were excluded from panels by the FDA.

''These are large conflicts of interest. At least some of them ought to be grounds for recusal," said Peter Lurie, lead author of the JAMA article and deputy director of Public Citizen's health research group.

Susan Bro, an FDA spokeswoman, said the agency is committed to a ''strict code of ethics" and a ''transparent process."

As it assembles advisory panels, ''the FDA carefully weighs any potential financial interest with the essential need for world-class scientific expertise," Bro said. ''Only in this way can the agency protect and advance the highest standards of public health."

In January 2002, the FDA began releasing more details at meetings where votes were taken on specific products. The move came just months after Public Citizen threatened a lawsuit to prompt detailed disclosure of federal advisers' financial interests.

But the change in policy ''has had little impact on rates of recusal, restriction, or disclosed conflict," the five study authors concluded.

In fact, the agency now rarely discloses the name of rival drug companies when its advisers have financial ties to competitors, according to the JAMA article. Three years ago, it provided competitors' names 54 percent of the time.

Even some members of the public and patients who stepped to the microphone during the public hearing portions of the FDA meetings analyzed by Public Citizen voluntarily disclosed financial ties to drug companies -- often the sponsor seeking approval of a new treatment. All told, 29 percent of federal advisers and consultants reported financial ties to drug companies, compared with 37 percent of patients and other public hearing speakers, the article said.

Consumer advocates said FDA advisers with financial conflicts erode public confidence in decision-making. Drug regulators should work harder to recruit outside experts who do not have industry ties, FDA critics say.

Indeed, the Center for Science in the Public Interest says the FDA should delay a meeting scheduled for this morning on rewording labels for high blood pressure drugs because nine of the expected 12 panel members have drug industry ties.

Merrill Goozner of the Center for Science in the Public Interest said FDA advisory panels are often ''unbalanced." With or without drug industry ties, the FDA's experts ''are biased toward approving new therapies," Goozner said.

Bro, the FDA spokeswoman, said the agency will not delay the meeting.

''No one participates in an advisory board capacity until they have been fully vetted by FDA staff and we are convinced they will make an unbiased, productive contribution to the scientific process," she said.

This spring, the FDA is expected to decide whether multiple sclerosis patients can again buy Tysabri, a drug voluntarily pulled from the market by its manufacturers -- Biogen Idec of Cambridge and its Irish partner Elan Corp. -- after it was linked to a potentially fatal brain infection. The FDA granted conflict waivers to five of 12 federal advisers who unanimously recommended the FDA return the drug to the market.

The JAMA paper comes, however, as members of Congress prod the agency to weed out advisers with drug industry connections.

''Allowing individuals with conflicts of interest to serve on advisory panels endangers the welfare of the American people," said Representative Maurice Hinchey, Democrat of New York.

Hinchey wants to eliminate such conflicts because they create ''an environment in which pure objectivity is lost and drugs that may not be safe wind up in homes across the country," he said.

Despite its finding that advisers with conflicts had a ''weak" impact on votes to approve or reject specific drugs, Public Citizen endorses the same zero-tolerance goal.

''The whole point of conflict of interest is that it's unconscious," Lurie said. ''Most of these people -- if not all -- are honorable enough people, they would not allow themselves to be influenced. It's the unconscious we need to be afraid of."

Diedtra Henderson can be reached at dhenderson@globe.com.

http://www.boston.com/business/healthcare/articles/2006/04/26/study_rebuts_conflict_fears_around_fda?mode=PF

Serono "neutral," estimates raised
newratings.com - USA
... by Serono is likely to include late-stage pipeline products, given the company’s financial dependence on Rebif and potential competition from Tysabri in the ...

Earnings Preview:Biogen Idec
BusinessWeek - USA
... resume sales of multiple sclerosis drug Tysabri, however the agency delayed making a final decision until June on the drug, which was pulled from the market ...

Healthy relatives could hold key to cure disease (ANSA) - Rome, April 19 - Italian scientists have made a breakthrough in multiple sclerosis research, showing that healthy relatives may hold the key to a long-elusive cure for the often devastating condition .

The brains of healthy family members have similar lesions to their relatives with MS but their cerebral tissue seems to have reacted to protect itself, a team led by Maria Giovanna Marrosu of Cagliari University and Nicola De Stefano of Siena University say .

"At first sight the damage to the nerve-cell sheaths appears the same," Marrosu said in a paper published in the Annals of Neurology .

"But once you look closer, you see that the MS sufferers have another set of fuzzier alterations," she explained .

"We already know the brain is able to repair itself. There's something in the healthy ones that protects the nervous system" .

"Perhaps it has something to with a greater plasticity. Anyway, once we find out what it is we may have the key to eliminating the disease" .

Marrosu and De Stefano studied some 400 individuals - half healthy, half with MS - for three years .

They were all around 30-40, the typical age of onset of MS .

At the end of the test period, only one of the healthy subjects had developed the disease and most of the sample had gone past the riskiest age .

"We're pretty sure we can establish the differences between the healthy ones and their less fortunate relatives," said De Stefano .

"Those protective factors could spell the end of MS" .

MS is a lifelong chronic disease diagnosed primarily in young adults, who retain a virtually normal life expectancy .

Estimates suggest that there are 2.5 million people living with MS and that women are twice as likely to be affected than men. Persons living with MS describe changes in sensations, visual problems, muscle weakness, depression, loss of bladder control, dizziness, pain and difficulties with walking, clumsiness and halting speech .

Scientists have learnt a great deal about MS in recent years. But its cause remains elusive. Many investigators believe MS to be an autoimmune disease - one in which the body, through its immune system, launches a defensive attack against its own tissues. The 'non-aggression pact' between the body and its immune system goes awry. The immune system wrongly identifies parts of the body as a foreign threat and declares war. In the case of MS, it is the nerve-insulating myelin that comes under assault. This may be linked to an unknown environmental trigger - a common virus called Epstein-Barr virus seems the likelist candidate. Multiple sclerosis can range from relatively benign to devastating, as communication between the brain and other parts of the body is disrupted. There are also different forms of the disease. Twenty years ago, MS sufferers faced a hopeless future of long confinement to a wheelchair within 30 years of diagnosis. However, in the last decade, treatment has changed dramatically. There is still no cure but disease-modifying drugs now slow the progression and control symptoms of the disease .

http://www.ansa.it/main/notizie/awnplus/english/news/2006-04-19_1196865.html

JK Rowling And The MS Society Scotland Fund A New Multiple Sclerosis Research Centre In UK
Medical News Today Sat, 22 Apr 2006 1:02 AM PDT
The University of Edinburgh is to form a Scottish Multiple Sclerosis research centre - the first of its kind in the UK - to build on previous work at the University into the devastating condition. Scientists in Edinburgh will strengthen links with other international and UK MS experts to push forward understanding of the disease... click link for more info.

Multiple Sclerosis Drug Advances Medical News Today Fri, 21 Apr 2006 4:03 PM PDT Two studies highlighted advances in treatment of multiple sclerosis (MS). The experimental drug FTY720, derived from a Chinese herb and currently in clinical trials, demonstrated its ability to reduce lesions in the brain, and to reduce the number of relapses patients experience over the course of the year... click link for more info.

Health Researchers Probe Sleeplessness, Depression, and Multiple Sclerosis
Government of Canada News Thu, 20 Apr 2006 11:59 AM PDT
The Honourable Lawrence Cannon, Minister of Transport, Infrastructure and Communities and Member of Parliament for Pontiac, on behalf of the Honourable Tony Clement, Minister of Health, highlighted today along with Dr. Alan Bernstein, President of the Canadian Institutes of Health Research (CIHR), the recipients of an investment of over $81.5 million to fund health research in Quebec.

New waiver law fails to quiet criticism over experts' financial ties to drug companies

By Diedtra Henderson, Globe Staff | April 21, 2006

WASHINGTON -- When a Food and Drug Administration panel of a dozen experts voted to bring back to market the multiple sclerosis drug Tysabri, five had financial ties to the drug's maker, Biogen Idec Inc., or one of its competitors.

The financial ties were disclosed under a law passed last November meant to limit industry influence on the FDA's actions. The law doesn't bar doctors, researchers, statisticians, and other experts from participating if they have received drug company money. Instead, the FDA can grant them waivers but makes the experts disclose those financial ties.

Managing conflicts of interest that accompany top scientists is a juggling act the FDA has been doing for years. The new law was supposed to make it better without grinding FDA approvals to a halt. Since the law was passed, the FDA has issued nearly 100 waivers -- and the controversy hasn't faded.

Critics say the new transparency has changed little and scientists who have conflicts of interest can still guide FDA decision making. The FDA counters that public health would suffer if the agency bypassed the nation's best scientists because of funding sources.

''All behavior is guided by both conscious and unconscious motives," said Dr. Karl Kieburtz, the Tysabri advisory committee chairman who is also a consultant to Biogen. ''Consciously, I'm not aware of any swaying of my decision-making based on the fact I did consulting for Biogen Idec within the last year."

A neurology professor at the University of Rochester, Kieburtz voted to return Tysabri to the market. The FDA doesn't have to follow the advice of its panels but usually does. Biogen, based in Cambridge, marketed Tysabri with an Irish partner, Elan Corp. The companies voluntarily pulled Tysabri off the market after the drug was linked to a potentially fatal brain infection.

The panel unanimously agreed in early March to bring Tysabri back and said in a 7 to 5 vote that patients could use it first, rather than after trying older therapies. The FDA is expected to disclose its final decision as early as this spring.

The FDA reports panelists' financial ties in broad categories, such as less than $10,001 per year, and from $10,001 to $50,000 per year. The disclosure on the FDA's website says Kieburtz received $10,001 to $50,000 in the prior 12 months from the drug's sponsor and less than $30,000 per year as a consultant for three Biogen competitors.

In an interview, Kieburtz offered more specific information, saying he received no more than $12,000 from Biogen, and that his consulting does not have to do with MS or Tysabri.

Kieburtz said he gave the payments to the University of Rochester or to charities. Another FDA adviser on Tysabri, Dr. Steven DeKosky, the chairman of the University of Pittsburgh Medical School's department of neurology, agrees with the FDA that federal advisers with no experience running clinical trials -- which by their nature are often funded by drug companies -- could do the public a disservice.

DeKosky said he didn't know he had a conflict until he filled out the FDA's disclosure forms in which he had to list all work he'd done recently for the industry. The FDA advisers report past and present financial ties to drug companies, and future financial interests they are negotiating. On it, DeKosky disclosed he'd received less than $10,001 as an industry sponsored speaker and was paid less than $10,001 by Pfizer Inc. as a visiting professor. Until the FDA issued his waiver, DeKosky said he did not know a rival MS drug is made by a company that has a financial agreement with Pfizer.

''It certainly didn't enter into any of my thinking. I am supposed to have a reputation as a honest, straight-shooting guy," he said.

The Center for Science in the Public Interest, Washington-based consumer advocates, argues advisers should be independent and the FDA shouldn't grant any waivers.

''Period. End of story. Get rid of scientists with conflicts from serving on the FDA advisory panels," said Merrill Goozner, director of the center's Integrity in Science project.

Dozens of times each year, the FDA empanels advisers plucked from academic institutions, government agencies, and industry. The advisers read stacks of documents before meetings and sit through hours of complex scientific presentations and often emotional testimony from patients. The experts cast votes on such questions as whether to strengthen warning labels for antidepressants and attention deficit remedies taken by millions or whether to lift sales restrictions on silicon gel breast implants. Industry representatives on the panels cast nonbinding votes.

The new law was spurred by high-profile hearings last year on a troubled class of painkillers that included Bextra, Celebrex, and Vioxx. The FDA came under congressional fire for permitting federal advisers who had accepted money from makers of those drugs to vote on whether the painkillers should be sold. In response to the new law, the FDA now posts conflict notices for its advisers on its website in advance of meetings.

Andrew von Eschenbach, the FDA's acting commissioner, said during a recent congressional hearing that the FDA's push to attract the best experts leads to senior scientists who receive drug industry sponsorship. Barring those researchers would result in smaller panels with less expertise.

''I do not believe that it is a process where we simply can exclude or ignore anyone who has remotely been associated with any organization or any program that's relevant to the subject matter," von Eschenbach testified. Barring those scientists would ''undermine the ability to have the best minds make the best decisions."

MS, a disease of young adults, disrupts communication between the brain and other parts of the body, resulting in symptoms that can intensify with little warning. Some have difficulty concentrating, remembering or making decisions. Others are rendered unable to speak, write or walk.

Current drugs and experimental therapies aim to reduce the number of exacerbations in hopes of slowing the progression of physical disability. Because Tysabri worked well in curbing flare-ups, some patients clamored for its return.

Other Tysabri advisers reached by The Boston Globe who received FDA waivers said drug industry funding did not influence their votes.

Dr. Lily Jung, the medical director of the neurology clinic at Swedish Neuroscience Institute in Seattle, received $10,001 to $50,000 in the previous 12 months from Biogen and less than $20,000 from two rivals with competing MS drugs as a speakers' bureau member. Jung, the consumer representative on the panel, said she advocates for MS patients, not the companies selling MS drugs that sponsor her talks. ''I don't think it conflicts at all."

Dr. Ralph L. Sacco, a Columbia University neurologist, did not return several calls seeking comment. According to the FDA, Sacco received less than $10,001 in consulting fees in the previous 12 months from a Biogen competitor.

Dr. Larry B. Goldstein, a Duke University neurologist, received $10,001 to $50,000 in the previous 12 months from one Biogen competitor and less than $10,001 per year from another rival for consulting work unrelated to MS. He said drug company funding did not impact his vote ''one way or the other."

Diedtra Henderson can be reached at dhenderson@globe.com.

© Copyright 2006 Globe Newspaper Company.

http://www.boston.com/business/healthcare/articles/2006/04/21/no_end_to_fda_disclosure_debate/?page=full

April 18, 2006

News and notes

A survey of 200 patients in West Palm Beach, Fla., with a type of multiple sclerosis known as relapsing remitting has found that more than half would definitely or probably use a drug that significantly reduces frequency of relapse or progression in disability even if the drug involves a 1-in-1,000 chance of a fatal side effect.

The survey was conducted by John E. Calfee for the AEI-Brookings Joint Center for Regulatory Studies, established by the American Enterprise Institute and the Brookings Institution.
Those interviewed suffered substantial disability, most of them requiring a wheelchair or support for walking any significant distance, and over half suffering relapses in the past year. All were on drug therapy, while half had switched drugs and one-third had switched at least twice.
An FDA expert panel recommended unanimously last month bringing back Tysabri. The drug was pulled from the market in February.

http://www.indystar.com/apps/pbcs.dll/article?AID=/20060418/LIVING01/604180304/-1/ZONES04

By Randall Osborne

West Coast Editor

Less than two months after disclosing its plan to sell $23 million in stock through a private placement to push along its Phase IIb trial with Tovaxin for multiple sclerosis, PharmaFrontiers Corp. has closed the deal and is planning a 1-for-10 reverse stock split that would let the firm apply for a Nasdaq listing.

The money gives The Woodlands, Texas-based PharmaFrontiers enough cash to last through the third quarter of next year, said CEO David McWilliams, "enough time to get the enrollment done and the interim analysis."

About 23 million units were sold to institutional and other accredited investors at $1 each, comprising two shares of newly issued common stock and a five-year warrant to buy another share at an exercise price of 65 cents. Whether the firm will raise more money after reporting the interim data is unclear.

"We're going to be investigating alternatives, including maybe taking a partner," McWilliams said.

PharmaFrontiers' stock (OTCBB:PFTR) closed Monday at 57 cents, up 5 cents.

The Phase IIb trial with Tovaxin, the MS vaccine for which most of the stock-sale proceeds will pay, is expected to start this quarter. Funds also will be used to finish preclinical development and start human trials with the company's therapies for rheumatoid arthritis and Type I diabetes.

Touted as a drug that goes after the causes rather than symptoms of MS, patient-specific Tovaxin works along the same lines as autologous cancer vaccines, but consists of attenuated autoreactive T cells, rendered non-replicating but viable, that are intended to bring about an immune response when injected subcutaneously in a five-shot course of treatment at the start, four weeks, eight weeks, 12 weeks and 24 weeks.

That immune response is directed specifically against T cells within the patient that are self-reactive with myelin, rather than restricting all T cells from the central nervous system.

A broader approach for MS could mean trouble. Witness Tysabri (natalizumab), the compound from Cambridge, Mass.-based Biogen Idec Inc. and Elan Corp. plc, of Dublin, Ireland. The partners voluntarily pulled Tysabri off the market last year after the drug was linked to progressive multifocal leukoencephalopathy, a potentially fatal disorder, and the FDA has yet to decide whether selling can resume.

"Tysabri, we think, was a very good proof of principle for our approach," McWilliams told BioWorld Today. "When you keep these leukocytes out of the central nervous system, you do seem to have a pretty strong clinical effect, [but Tysabri] compartmentalizes all leukocytes, which is the problem, while we're honed in on a specific cell type. We don't disturb the rest of the leukocytes."

Side effects with Tovaxin thus far are fewer than with Tysabri, he added, and are limited to slight injection-site reactions.

"I think we're still easier to use," McWilliams said, though the company is refining its dosing regimen. Tysabri was given as a one-hour infusion every month, while Avonex (interferon beta-1a), also from Biogen Idec, is dosed weekly, and Copaxone (glatiramer acetate), from Teva Pharmaceutical Industries Ltd., of Jerusalem, is given daily.

"We'll probably approach the [FDA regarding Phase III trials] once we have the interim data" from the Phase IIb with Tovaxin, McWilliams said, noting that regulators thus far have allowed the company to proceed even though a Phase I/II study has yet to finish. That trial is expected to complete at the end of this year, he said.

PharmaFrontiers' RA compound is "built on the same principle as Tovaxin," except that cells are isolated from synovial fluid, in a method invented by the same scientist who came up with the MS approach. A "highly encouraging," 15-patient trial has been done in China, McWilliams said, but the data have not been released yet.

In diabetes, the company has figured out how to "take a monocyte, evolve it to a stem cell, and then into a pancreatic eyelet cell," he said. "In vitro, those data look extremely exciting."

PharmaFrontiers at the end of March reported a net loss of $19.4 million, or $1.24 per share, for 2005, compared with a net loss of $4.6 million, or 73 cents per share, for the previous year. Research and development expenses for 2005 totaled about $9.9 million (compared to about $2.5 million in 2004), due mainly to Phase I/II work with Tovaxin.

The company's board of directors has approved the 1-for-10 reverse stock split, also disclosed Monday, and will recommend shareholders give it their blessing. In the private placement, MDB Capital Group LLC in Santa Monica, Calif., acted as the exclusive agent.

http://www.bioworld.com/servlet/com.accumedia.web.Dispatcher?next=bioWorldHeadlines_article&forceid=38831

April 7, 2006; Page A12

"Every day I'm a little bit worse," Audrey Greenfield tells us. The former New York law partner used to travel the country representing real estate developers. But the multiple sclerosis that she first noticed 15 years ago when she lost coordination in her right foot has now progressed to the point she needs a wheelchair. And she isn't comforted by the fact that she's being denied an effective treatment by the Food and Drug Administration, which is once again harming patients with overcaution.

The therapy in question is Tysabri, and for many MS patients it appears to halt progression of the degenerative neurological disorder. But a year ago -- just months after it was approved -- corporate partners Biogen and Elan "voluntarily" withdrew their drug because of FDA pressure and litigation fear after two patients developed a rare brain infection. That infection might have been linked to Tysabri, since the drug works by suppressing parts of the immune system. But these patients also had other immuno-suppressive therapies, and in any case the MS patients were almost all willing to run the risk.

Just a few weeks ago prospects were looking better for Ms. Greenfield. She and scores of other MS patients had made their voices heard at an FDA advisory panel, which voted unanimously to return Tysabri to the market. The agency was due to rule on the issue by late last month.

But shortly before the deadline, the FDA announced it would take a 90-day extension until the end of June because of concerns over Tysabri's "risk management" plan -- a preposterous excuse given that Tysabri is delivered by injection and only under the supervision of doctors. With its delay, the FDA is denying very-well-informed doctors and patients the freedom to "manage" the risks of untreated MS. "I haven't had any treatment in over a year," says Ms. Greenfield, who got one injection of Tysabri before it was withdrawn.

Bartira Tibertius of Chicago faces the same predicament. She received Tysabri for a full 28 months as part of a clinical trial. "I was doing great. I even forgot that I was sick," Ms. Tibertius, a language teacher and translator, tells us. "But now I'm getting very, very scared. It's deteriorating and I know that," describing numbness and tingling in her hands, arms, feet and face. As for any possible risks from the drug, she says, "I'm more scared of not having Tysabri than having Tysabri. If you told me the Tysabri would shorten 10 years of my life I would do it. I want quality of life, not quantity."

Her risk-benefit analysis is backed by the latest scientific evidence. Several recent studies reported in the New England Journal of Medicine conclude that, among other benefits, Tysabri appears to cut the number of new or expanding brain lesions in MS patients by 83%, and for many induces near-complete remission. Yet the FDA was unable to get its act together and meet its March deadline. It's still likely that Tysabri will return to the market, but the agency's apparent nonchalance in the face of progressive neurological damage is a sad spectacle.

One lesson is that Tysabri should never have been withdrawn in the first place, when a "Dear Doctor" warning letter would have sufficed. But the possible side effects came to light at the height of the Vioxx panic (another relatively small risk, by the way), and then-acting FDA chief Lester Crawford wasn't going to take any difficult stands while he was awaiting confirmation. We hope Andrew von Eschenbach, the latest nominee to head the FDA, won't follow Mr. Crawford's lead. The FDA badly needs public leadership to explain that almost all live-saving and life-improving drugs do have some risks.

The Tysabri story is also further evidence of the need for Congress to pass "Kianna's Law" -- legislation introduced by Senator Sam Brownback (R., Kan.) that would require the FDA to move faster on drugs for terminal and degenerative disease. The tendency of FDA bureaucrats is always to delay decisions on drugs that might turn out to have some nasty side effects. But as Audrey Greenfield, Bartira Tibertius and thousands of other MS patients have had to learn over the past year, too much caution can have nasty side effects too.

Permalink/Main

4 Comments:

This really is analagous to the notion of informed consent to surgery. Bad things happen in a small percentage of operations, but people give informed consent to the procedure having been informed of the risks.

Why not have Tysabri users sign a similar form, and waive certain tort rights they might otherwise have pursued?

By Cardinalpark, at Fri Apr 07, 10:12:46 AM

I can tell you why: because some clever attorney will allege their "consent" was not really informed or was made under duress or strain of illness.

This is what aggravates me so about the legal profession: we have made it so easy to sue that the ease of litigation is now backfiring on plaintiffs.

It is madness. Adults should be presumed to be capable and informed unless there is some pretty damned strong evidence otherwise: the BOP should be on the plaintiff in this case to prove why their "consent" was not informed or voluntary or why they were incompetent, and that ought to be a very, very steep evidentiary mountain to climb.

Otherwise, medical decisions are taken out of the hands of patients and their families and placed in the hands of government. Do we really want that? I know I don't.

By Cassandra, at Fri Apr 07, 10:20:54 AM

...almost all life-saving and life-improving drugs do have some risks.

Exactly. I doubt there is a drug that is absolutely safe in all instances. Aspirin would be considered a wonder drug if introduced today, and yet one wonders what the FDA would make of its link to Reye syndrome or its tendency to promote bleeding.

Using a drug provides benefit in the face of some risk. We accept the risk for the benefit. The choice of treatment should be left to doctors and patients, not to the vagaries of bureacratic meddling.

http://tigerhawk.blogspot.com/2006/04/fda-tysabri-conundrum-and-our-cultural.html

Fri Apr 07, 2006

Costs versus benefits of new drugs

The FDA and the Tort system give little weight to the benefit side of the ledger

Tigerhawk has a post discussing the case of Tysabri, a very effective drug for treating MS. He writes:

An example of this is the FDA's hanky-twisting over the multiple sclerosis drug Tysabri, which is orders of magnitude more effective against that nerve-killing disease than existing therapies. Unfortunately, Tysabri has been "linked" -- tenuously, at best -- with a rare brain infection in fewer than five patients out of the many thousands who have taken it. The FDA pressured Biogen and Elan to pull the drug last year, and it has not cleared the drug for relaunch notwithstanding the unanimous recommendation of a non-binding expert advisory panel. Why? Because it fears the quick death of one or two people more than it values the lifespans of hundreds of thousands of people.

Tigerhawk goes on to reprint a WSJ editorial on the subject. It concludes:

One lesson is that Tysabri should never have been withdrawn in the first place, when a "Dear Doctor" warning letter would have sufficed. But the possible side effects came to light at the height of the Vioxx panic (another relatively small risk, by the way), and then-acting FDA chief Lester Crawford wasn't going to take any difficult stands while he was awaiting confirmation. We hope Andrew von Eschenbach, the latest nominee to head the FDA, won't follow Mr. Crawford's lead. The FDA badly needs public leadership to explain that almost all live-saving and life-improving drugs do have some risks.

The Tysabri story is also further evidence of the need for Congress to pass "Kianna's Law" -- legislation introduced by Senator Sam Brownback (R., Kan.) that would require the FDA to move faster on drugs for terminal and degenerative disease. The tendency of FDA bureaucrats is always to delay decisions on drugs that might turn out to have some nasty side effects. But as Audrey Greenfield, Bartira Tibertius and thousands of other MS patients have had to learn over the past year, too much caution can have nasty side effects too.

It is strange how so much attention is paid to the possible deaths of a few people and so little to the lives lost that otherwise would have been saved. The same sort of lunacy has greatly reduced the number of vaccine manufactures, as this Wharton article notes:

Lawsuits filed against vaccine makers alleging their products have harmed patients are another reason drug makers have become wary of vaccine production, says Wharton health care systems professor Scott Harrington. With vaccines that can potentially reach millions of patients, the odds of a bad outcome in the courts could ruin a firm, he notes. In the case of widely distributed vaccines, "a firm is engaging in a bet-the-firm risk if things go bad. That discourages research and development on certain types of vaccines and discourages production and marketing."

In 1986, Congress created the Vaccine Injury Compensation Program (VICP), which established a no-fault system for compensating those who may have been injured by routine childhood vaccines. The program was designed to streamline and limit vaccine makers' liability. But Harrington says lawyers continue to bring suit against vaccine companies by using opt-out provisions in the legislation that created the VICP.

The biggest obstacle vaccine makers face, Harrington adds, is little payback for their risk because many of their products are purchased in bulk by governments and other public health authorities, including humanitarian agencies. These large buyers are able to negotiate low prices. "In the U.S., the government is paying for over half of all vaccines for children, and vaccine makers are more or less forced to take prices that are very low. It might be difficult to pursue research and development without worrying that you could get a very low price," says Harrington.
...
David also suggests that some of the vaccine shortages in recent years may have come as a result of stepped-up Food & Drug Administration review of vaccine manufacturers' plants. "The more serious the FDA got, the more shortages we got."

According to Danzon's vaccine study, Wyeth produced influenza vaccine for the U.S. market for more than 20 years, but in October 2000 the company was fined $30 million for manufacturing violations and an additional $15,000 for every day that it remained out of compliance. In November 2002, Wyeth announced it would exit the flu market, leaving only two manufacturers of injectable influenza vaccine.

David says the role of government in the vaccine market cannot be overlooked. Assertions that a market-driven system has failed in the vaccine industry are wrong, he suggests. "We do have private firms providing vaccines, but it's not like we have ever given this market a chance to be a free market. This type of production is among the most heavily regulated industries we have."

Excessive government regulation and rapacious lawyers are a potent combination if your objective is to destroy the pharmaceutical industry. The price we pay for the few lives saved are a thousandfold more dying and suffering the ravages of diseases like MS.

Posted by: Pat on Apr 07, 06 | 9:07 pm |

http://www.asininity.com/weblog/P2653/

PharmaFrontiers takes on private placement to spur reverse stock ...
Houston Business Journal - Houston,TX,USA
... PharmaFrontiers intends to use the proceeds to fund its Phase IIb trial with Tovaxin for the treatment of multiple sclerosis, which is scheduled to begin this ...

NEWS AND TIPS FOR GOOD LIVING
Healthful Advice Patients want freedom to pick risky drug
Posted on Sat, Apr. 15, 2006

A survey of 200 patients with a type of multiple sclerosis known as relapsing remitting has found that more than half would definitely or probably use a drug that significantly reduces frequency of relapse or progression in disability even if the drug involves a 1-in-1,000 chance of a fatal side effect.

The survey was conducted by John E. Calfee for the AEI-Brookings Joint Center for Regulatory Studies, established by the American Enterprise Institute and the Brookings Institution.

Those interviewed suffered substantial disability, most of them requiring a wheelchair or support for walking any significant distance, and over half suffered relapses in the past year. All were on drug therapy, while half had switched drugs and one-third had switched at least twice.

Willingness to tolerate risk bore little relationship to disability levels. A substantial majority agreed the FDA should tightly control drugs with safety concerns, but a larger majority agreed that once the FDA has provided a warning, patients should be free to decide with their physician whether to use such drugs.

After the FDA has reviewed drug safety and provided reasonable warnings, many MS patients say they wish to be free to choose to incur a 1-in-1,000 (or even greater) risk of a fatal side effect in return for significantly more effective drugs, and are willing to work with their physicians in doing so.

Despite estimates that it kills one patient in a thousand, an FDA expert panel recommended unanimously last month bringing back the multiple sclerosis drug Tysabri. The drug was pulled from the market in February.

http://www.myrtlebeachonline.com/mld/myrtlebeachonline/living/home/14349386.htm?source=rss&channel=myrtlebeachonline_home

Albany man explains his confusing, lengthy battle for MS drug coverage

By MATT PACENZA, Staff writer
First published: Thursday, April 13, 2006

ALBANY -- Tom Copeland did everything right.

The 55-year-old Albany man signed up early for Medicare Part D, excited that he had found a drug plan to help him pay for medication to keep his multiple sclerosis from worsening. He filled out every piece of paperwork and made every phone call.

But after months of dizzying denials and roadblocks, Copeland has discovered, months later, that the new Medicare drug program won't work for him. A co-pay that was supposed to be $3 is at least $211 -- way more than he can afford on his modest disability pay.

Copeland, who shares a South End home with his sister, is a relentless advocate for himself. He displays a massive stack of paperwork he has accumulated while battling Medicare and private insurance plans over recent months.

"From February till now, this has been my full-time job," said Copeland in his kitchen last week, waving a yellow legal pad. "And for what?"

Advocates for people with disabilities and people with MS said they have heard of plenty of problems like Copeland's.

"There have been so many screwups in terms of the information given out by Part D plans," said Kim Calder, the manager of the health insurance initiative for the National Multiple Sclerosis Society.

MS drug offers relief

The medication that Copeland has been taking, Rebif, is one of four drugs that helps ward off multiple sclerosis, an autoimmune disease that affects the central nervous system. MS varies widely, but it leads to symptoms such as vision problems, numbness, loss of bladder control, difficulty walking and spasticity. The symptoms tend to occur in periodic attacks, often brought on by stress.

The drugs, which work by modifying the immune system, are taken by about half of people with MS. "The evidence shows the drugs work," said Dr. Patricia O'Looney, the director of biomedical research programs at the National Multiple Sclerosis Society.

The medications cost between $16,000 and $24,000 a year, according to the National MS Society. Many people, even some with drug coverage, have a hard time affording Rebif and the other medications.

Copeland was diagnosed with MS in 1981. He's been relatively lucky so far, with only scattered episodes that affect his walking and speech.

"I've had to relearn how to talk and walk," said Copeland. "It isn't bad -- for me."

A native of New York City, Copeland attended college and worked as a bank officer and as a heating and air conditioning technician before his condition drove him to disability. He then qualified for Medicare, which funds coverage for seniors and people living with disabilities.

Copeland has been taking Rebif since December. It has worked, he believes. Stiffness in his neck has gone away for the first time in months, among other improvements.

In July, Copeland called a Medicare counselor to sign up for coverage. He was told that a plan from the First United American Life Insurance Co. would be the cheapest and best for him, with only a modest co-pay for Rebif.

It all worked at first. In January, he was charged a $30 co-pay, which he could afford. But then come February, he was charged $234.53.

Copeland immediately called the insurer. After several rounds of phone calls, he was told that $234 was the right figure. A First United spokesman did not return a phone call seeking comment on this story.

So he switched plans, as all Medicare Part D recipients are allowed to do one time.

A Medicare counselor again told him that the new insurer, United Health Care, had a minimal co-pay, of $5 to $20. But when the drug was actually shipped in March, the cost was $211. In April, Copeland just found out, it will go up to $233.

A spokesman for United Health Care did not respond to questions from the Times Union.

Copeland has finally figured out that the $233 is the right figure, after months of being told he would pay less.

A representative for the federal Centers for Medicare & Medicaid Services confirmed the bad news: At Copeland's income level, all plans include a 15 percent co-pay. If that's so, how come no one ever clearly told him that before? Why do the Web sites for the private health plans show much lower co-pays, according to Copeland?

"It should be pretty straightforward," said spokeswoman Danielle Liss. "I guess it depends on who he's talking to, on who the person is advising him."

System hard to fight

Copeland cannot afford the big co-pay. His only income is $1,071 a month in disability pay. Take away $300 for rent, $317 for utilities, $100 for the phone and there's just a little left for food and the rest.

"I get by," he said. "But I literally don't have $300."

Copeland's story shows how challenging the Medicare drug benefit can be. He is an educated man, with Internet access at home, with enough free time and wherewithal to spend hours a day interpreting small print and haggling on the phone.

Most people on disability don't have such resources, advocates point out.

"Part D is uniquely difficult for people with long-term disabilities," added Elizabeth Priaulx, a senior disability legal specialist with the National Disability Rights Network.

To Calder, the misinformation experienced by patients like Copeland points to a problem inherent in Part D, which has been widely criticized for its complexity.

"It was cobbled together by Congress at the last minute," said Calder. "When the people who are sickest and in the greatest need bear the greatest cost, there's something wrong with your system."

For now, Copeland is still on Rebif, because United Health Care gave him a one-time waiver on the big co-pay. His doctor might able to provide him some sample medication, but sooner rather than later, the drug will run out.

Copeland is disappointed -- and angry. And on the verge of giving up, especially because he fears the growing stress will bring back an MS attack.

"Forget it," he said Wednesday. "I have put in enough time on this. I'm going to get sick if I don't watch out. It's not worth it."

http://www.timesunion.com/AspStories/story.asp?storyID=471201&category=REGION&newsdate=4/13/2006

Research aimed at degenerative diseases Labs across Canada take part in effort
Apr. 6, 2006. 01:00 AM
ELAINE CAREY
TORONTO STAR STAFF REPORTER


Janet Rossant's stem-cell research may one day help our bodies heal themselves.

As chief of research at The Hospital for Sick Children, Rossant is collaborating with labs across Canada to see whether human embryonic stem cells can be useful tools for treating degenerative diseases. Her lab at Sick Kids is looking at trying to get stem cells to form blood vessels that could be transplanted into the damaged tissue of patients with heart disease.

Stem cells have become a crucial area of research at the hospital, as investigators try to use them to understand and fight a variety of diseases.

Rossant is the award-winning discoverer of early cells that form the human placenta. She showed several years ago that you can generate mice entirely derived from embryonic stem cells, provided you mix them with a normal embryo.

"It's still an amazing thing to think about," she says. "You can actually take cells, put them in a Petri dish and genetically alter them to create genetically altered mice."

Those mice are created to mimic human diseases. Mice produce only two types of cells: a group that forms the placenta, and a group of about 15 cells called the inner cell mass that forms the mouse itself.

Rossant's team has been able to develop stem cells from both types of mouse cells, "which gives us enormous biological tools to study these two lineages," she says. "We're using it to understand how the embryo makes the decision to make either a very potent cell or a placental cell."

Her research is moving into the more controversial area of using human embryonic stem cells from stem-cell lines approved for use in Canada, to see whether the same mechanisms are at work as in the mouse.

"At this stage, we're still at the exploratory phase where we need to understand the power of stem cells, how best to grow them in culture and keep them normal, which is one of the critical issues," she says.

If the information they derive from embryonic stem cells can be applied to adult ones, they could be grown in culture and would become important tools for understanding human biology and developing new drug targets that can interfere with stem-cell survival.

"Then stem cells themselves won't be used in therapy but we will use the information to help drive our own bodies to fix themselves," she says.

"That's certainly the long, long-term goal."

Freda Miller's lab has shown that stem cells found in adult skin retain the capacity to make many different types of cells. Now it's focused on using these cells to find ways of treating devastating diseases of the nervous system, and also spinal cord trauma.

The work began because the only human source for brain stem cells is either aborted fetuses or human embryonic stem cell lines. While Canadians have agreed it's ethically acceptable to use them, "I think most people would prefer not to if they didn't have to," she says.

Even using those cells, "You're talking about putting cells into people that don't belong to them," she says. "If we had a 17-year-old spinal cord injury victim and we could show they could be treated with stem cells, then we would probably be faced with immuno-suppressing him for the rest of his life."

Her lab is trying to find a source of stem cells that come from thepatients themselves and that come from adult tissue so they won't have to deal with the ethical issues of using embryos.

"What we have now is this population of human cells that can make multiple kinds of cells, including cells involved in the nervous system," she says. "Now we're asking: `Are they functional, can we put them back in the animal?'"

---

One of the cells produces myelin, the sheath that wraps around most of the nerves in the body and that's lost in multiple sclerosis and many traumatic brain and spinal cord injuries.

The lab, in collaboration with the Rick Hansen Centre for spinal cord injury research in British Columbia, has shown that you can put those cells in animals and they produce functional myelin that encourages the growth of nerve cells that have been damaged and injured.

"We're very excited. It looks like our cells can do everything we hoped they could do," she says. While the work is all in animal models, the next step is to try it on humans.

---

Dr. Peter Dirks' lab made the breakthrough discovery that a small number of cells in a brain tumour control its growth. They have been able to take those cells, inject them into mice and replicate the human brain tumour. That has led to research to define what those cells are and what drugs can be used to destroy them.

"Based on our work, this idea has really caught on and many groups all over the world are thinking about brain tumours in this way so that's pretty exciting," Dirks says.

Brain tumours are hard to treat because radiation can only be given in limited doses or it kills the surrounding brain cells, causing long-term cognitive damage. Even with measured doses, it has serious effects on learning and memory function — even in children — over time, he says.

"With chemotherapy, the brain is a relatively privileged site," he says. "It's designed not to allow drugs or other substances into its milieu, so even to get a chemotherapy agent that can get into the brain and have a chance of being effective, is difficult.

"We really need to find treatment that's more selective and that's going to be another big challenge — how to target tumour cells as opposed to normal stem cells in the brain.

``At this point, we don't even know what stem cells are doing in our brain but their mere presence suggests they can go bad to form a brain tumour. But it may be a completely different cell that initiates that in a child and an adult."

Work on cancer stem cells is being hotly pursued in almost every type of human cancer, he says.

"That's the real challenge now, to figure out what makes them tick and how to shut them down. We have to find the tumour cells that really matter."

Breakthrough for Lupus/MS Sufferers
Experimental stem-cell treatment relieves many symptoms of Lupus sufferers.
http://abcnews.go.com/Video/playerIndex?id=1825674

BY PETER BENESH

INVESTOR'S BUSINESS DAILY

Posted 4/13/2006

When a drug gets pulled off the market because a relatively few patients have adverse reactions, plenty of other patients lose a treatment that might help them.

A couple of recent surveys show that patients want the right to decide for themselves whether to use potentially risky drugs for chronic diseases.

One of the surveys was from the American Enterprise Institute for Public Policy Research (AEI), a think tank that polled multiple sclerosis patients.

The other, from the National Consumers League, an advocacy group, polled a cross section of the national population.

In both surveys 90% of respondents said patients, in consultation with their doctors, should be able to choose a prescription drug that might have side effects.

Patients don't want the Food and Drug Administration restricting drugs that might benefit them, says John Calfee, an AEI resident scholar and author of its report.

"Once patients know the risks, they really think that the decisions should be made by them and their doctors," Calfee said.

The AEI survey was paid for by Biogen Idec, (BIIB) which, with Elan, (ELN) partnered to make the MS drug Tysabri.

The companies pulled the promising drug off the market in February 2005 after two deaths from a rare brain disorder that might have been caused by a drug combination.

Costs/Benefit Analysis

Tysabri exemplifies the right-to-choose issue, says Greg Simon, president of FasterCures, an organization that lobbies for quicker drug approvals. He says the FDA should analyze facts about drug efficacy and risk, then leave it to patients and doctors to decide about use of a drug.

"The FDA communicates risks on extremes of a curve," Simon said. "It either tells people the drug is safe, or it tells them the drug will kill enough people that everyone thinks they're in danger. We must separate the drug analysis function from the risk analysis function."

That position is shared by Biogen, which is campaigning to get the FDA to re-approve Tysabri.

"We want patients and physicians to have the option to have access to Tysabri, together weigh the product's risks and benefits, and then make decisions about therapy," spokeswoman Amy Brockelman said in an e-mail.

Biogen executives would not comment.

The FDA, which also wouldn't comment, has said it will decide Tysabri's future in late June. The release of the AEI survey coincided with a unanimous recommendation from an FDA panel to restore Tysabri to the market.

It's not hard to figure out why Biogen and Elan want the drug reinstated. Biogen's stock traded near 67 before Tysabri was pulled. After it was pulled, shares crashed 44% to less than 38. Now they trade near 45.

Elan's stock traded near 27 before the withdrawal. It fell as low as 3 in April 2005 and now trades near 14.

Biogen underwrote the AEI study because it wants to bolster its argument before the FDA, Calfee says. "Their purpose is to show that some MS patients are willing to take some chances to get a drug that's more effective than other therapies."

Calculated Risk

When FDA officials make these kinds of rulings, they should weigh various ethical questions, says Michelle Mello, associate professor of health policy and law at Harvard University.

"Is it fair to make a decision that looks at an overall effect of a drug on a population, and binds subgroups of that population to that decision even if the results for them might be different and possibly better?" she said. "Is it fair to impose a burden on some groups of very sick patients?"

She says some patients are so sick, they have nothing else to lose. "For them, our assumptions about wanting people to weigh all the evidence go out the window."

One advocacy group is suing the FDA over a related issue. The Abigail Alliance for Better Access to Developmental Drugs wants desperately ill people to be able to get drugs that have proved their safety but are still in clinical trials for efficacy.

The Tysabri case shows how the cost of not allowing some risks can be too high, says Frank Burroughs, president of the Abigail Alliance.

"If there's a .01% chance of a lifeboat sinking, do we let everybody go down with the ship?" he said.

Before patients can have a right to choose risky drugs, they should be required to sign waivers, Burroughs says. And most everyone agrees that patients should be willing to relinquish certain rights in order take certain risks.

"In order to make their own decisions, patients must give up the right to sue drug companies," Simon said.

Related Resources:

Search for previous IBD articles on this topic in the IBD Archives.

Read about innovative companies with promising futures in The New America.

Keep tabs on new products, innovations and market-moving trends with our Internet & Technology section.

http://www.investors.com/editorial/IBDArticles.asp?artsec=22&issue=20060413

Friday, April 14, 2006
Reported November 22, 2004
By Shari Levine, Ivanhoe Health Correspondent

(Ivanhoe Newswire) -- Vaccines are often considered responsible for the eradication of a number of infectious diseases that once killed millions of people and left many with chronic disabilities. “When I was a kid in the 1950s, the big fear was polio. Everyone knew someone on an iron lung, but today polio is rare and exotic,” says Myron Levine, M.D., D.T.P.H., a vaccine expert and director of The Center for Vaccine Studies at the University of Maryland School of Medicine.

Today, scientists continue to improve the quality of immunizations by:

* Creating new delivery methods
* Systematically monitoring safety and effectiveness
* Developing ground-breaking vaccines for diseases that in some way involve the immune system

Part I: No More Shots

All children in the United States are required to have more than a dozen immunizations before they enter school. As a result, vaccinations have been extraordinarily successful in reducing the rate of infection from once fatal diseases. In developing countries the high cost, lack of refrigeration, and limited supply of needles make it impossible to provide vaccines to millions of needy people. In 1990 the Children’s Vaccine Initiative was developed at the World Summit for Children in New York City. The Initiative supports development of new technologies for the creation of painless, less expensive, and more accessible vaccines.

EDIBLE VACCINES

Injected vaccines stimulate an immune response in the bloodstream. Edible vaccines created out of genetically modified plants could be used to build protection in the immune cells along the nose, throat and mouth where many air-borne germs first enter the body.

Potatoes: Researchers across the United States are looking for innovative ways to create safe and effective edible vaccines. One of the pioneers in this technology is Charles Arntzen, a plant biologist at Arizona State University in Tempe.1 He was one of the first scientists to create an edible potato vaccine, but his potatoes worked only when they were eaten raw. Arntzen is researching a way to make his vaccine-containing potatoes elicit an immune response after they are cooked.

In 1998, William Langridge, Ph.D., of Loma Linda University in California, genetically engineered potatoes to carry a vaccine against cholera.2 Unlike Arntzen’s earlier versions, this potato can be cooked and still carry the intact vaccine. When Langridge fed the vaccine-containing potatoes to mice, they produced antibodies to cholera.

Also using potatoes to create an edible vaccine are Hugh Mason, Ph.D., from the Boyce Thompson Institute at Cornell University, and Carol Tacket, M.D., from the University of Maryland School of Medicine.3 Mason has successfully created transgenic potato plants that contain the vaccines for cholera, hepatitis B, E.coli, and Norwalk virus. Dr. Tacket is conducting the clinical trials to test Mason’s edible vaccines in humans.

Tomatoes: Mason is also working to develop a tomato plant that contains the hepatitis B vaccine. His goal is to make tomato juice powder from vaccine-containing tomatoes that would be reconstituted and served as a beverage in developing countries where refrigeration is unavailable.4

Dennis Buetow, Ph.D., of the University of Illinois Urbana-Champaign, is testing an edible vaccine for respiratory syncytial virus. RSV causes a pneumonia-type disease that affects infants, young children, and older adults. Until now there has been no successful vaccine against RSV.

Buetow and colleagues have genetically engineered tomatoes to contain the RSV vaccine. “Our idea is to use a new approach and produce an 'edible' vaccine which when eaten throughout the winter months, will continually prime the immune system to produce antibodies against the virus. The edible vaccine would be consumed as part of the diet, would eliminate the need for injection by needles, and could be produced locally, thus removing the need for long-term refrigerated storage and shipping,” says Buetow.

When laboratory mice were fed the vaccine-containing tomatoes, their bodies produced antibodies to RSV. Buetow believes that, while these results offer hope, the vaccine will not be available for human consumption for at least five to seven years.

Tobacco: Henry Daniell, Ph.D., from the University of Central Florida in Orlando, studies genetically modified tobacco plants capable of producing both vaccines for diseases such as cholera and proteins such as insulin to treat diabetics. “Tobacco is a model system that we use because it is easy to genetically manipulate. We are using nicotine-free tobacco plants that taste like spinach and laboratory mice like to eat it.”

Other researchers use potatoes, corn, bananas and tomatoes to produce edible vaccines, but Daniell says he prefers to study leaves because he says, “We can introduce 10,000 copies of the gene into the plant cell, and 50 percent of the total plant protein is the foreign protein that we added. We found that each genetically engineered plant produced the same amount of protein, which means that the dosage is the same.” Daniell published the results of his research in the January 2001 issue of Nature Biotechnology.

Safety: Opponents of edible vaccines have many concerns. The Organic Consumers Union is one group concerned about how scientists will control the dosage of edible vaccines. They worry that if people get too much vaccine it could be toxic. Too little, they say, could lead to disease outbreaks.

Daniell and many other scientists are concerned about the environmental impact of genetically altered plants mixing genetic material with other plants through their pollen. “Foreign genes that are introduced in the nucleus of the plant cell are contained in the pollen, and pollen should never carry the gene that is engineered,” says Daniell. He has developed a novel approach in which he works with the DNA from chloroplasts (a component of the cell that is the site of photosynthesis) instead of altering the DNA from the plant’s nucleus. While there is hope for an edible vaccine for humans, Daniell believes that edible vaccines will first become available for animals within the next three to five years.

Nasal Flu Vaccine: The biopharmaceutical company Aviron, Inc., hopes to make flu shots obsolete in the next few years. The company has developed FluMist, a nasal spray containing the flu vaccine. Kristin Nichol, M.D., from the Minneapolis VA Hospital, led the clinical trials of FluMist and published her findings in The Journal of the American Medical Association (July 13, 1999). Since FluMist was found to be safe and effective in eliciting an immune response, the company is now seeking FDA approval.5

Vaccine Patches and Band-Aids: A simple patch may one day take the of place shots. Scientists are working on vaccines made of pure DNA that can be absorbed into the skin and elicit an immune response similar to that of injected vaccines. Large number of immune cells are found in the skin because it is the body’s first layer of defense against germs. Researchers from the Veteran’s Affairs Hospital in Palo Alto, Calif., and Stanford University are looking at a hepatitis B vaccine that would be applied directly to the skin as a shampoo or lotion.6

Gregory Glenn, M.D., at the Walter Reed Army Institute of Research, has been working with the Iomai Corporation on a DNA-based vaccine that is absorbed by the skin from a Band-Aid. The solution soaks into a layer of immune cells just under the surface of the skin that are normally bypassed by needles.7

Part II: The Vaccine Controversy

Year after year vaccines protect millions of people from sickness and death. However, this protection does not come without risks and rare adverse events. The safety and effectiveness of vaccines has come under fire from several concerned groups in the United States. One vocal skeptic of vaccinations is Representative Dan Burton, (R)IN. He is spearheading a complete review of the nation’s vaccination program.

Also concerned about the safety of immunizations is Barbara Loe Fischer, founder of the National Vaccine Information Center (NVIC) based in Vienna, Virginia. She started the organization after two of her children were injured by what she believes were complications from vaccines. In an interview published by the New York Times Magazine on May 6, 2001, Fischer says that while vaccines have helped to decrease the number of cases of childhood infectious diseases in the last 40 years, “We have at the same time seen a doubling of asthma and learning disabilities, a tripling of diabetes. Autism is affecting one in 500 children. We need to look at whether an intervention used with every child is perhaps contributing to the background rate of chronic disease and disability.”8

Fischer says that the NVIC is “Pro-education and pro-informed consent, not anti-vaccine. There is a difference. It is immoral to write off an unknown number of children as expendable in the name of the greater good to justify public health.”9

Vaccine and Disease: Is There a Link?

Public health experts are trying to determine whether or not certain diseases are caused by vaccines. For years, patients and their doctors wondered if the hepatitis B vaccine was linked to multiple sclerosis. In February 2001, a team led by Alberto Ascherio, M.D., from Harvard University School of Public Health, published a study in The New England Journal of Medicine that found no link between the hepatitis B vaccine and multiple sclerosis.10

Whether or not there is a connection between the measles, mumps, rubella vaccine and autism in children is perhaps the most highly debated question in vaccine science. The MMR vaccine is required in all 50 states before a child is admitted to public school or day-care centers. The vaccine has helped to control a common disease that once affected about 400,000 American children a year. In countries where the vaccine is not used, measles was blamed for about 1 million childhood deaths last year.

The MMR vaccine is generally given to children just prior to the second birthday. It is around this time that children display the signs and symptoms of autism. Concerns about a link between MMR vaccine and autism began when British researchers noticed that a few dozen autistic children had developed inflamed bowels after receiving the MMR vaccine, just prior to showing the first signs of autism. Andrew Wakefield, M.D., a British gastroenterologist, believes that he has discovered the missing MMR-autism link: The live virus from the MMR vaccine has damaged autistic children’s gastrointestinal tract allowing fragments of the measles virus to circulate in the blood and enter the brain.11 Harold Buttram, M.D., an outspoken physician in Quakertown, Penn., agrees with Dr. Wakefield’s theory that the link between MMR vaccine and autism is real.

Two recent studies found no connection between MMR and autism. One was published in the March 7, 2001, issue of The Journal of the American Medical Association. A team led by Loring Dales, M.D., found no link between the vaccine for measles, mumps and rubella (MMR) and the development of autism in children.12 In this study a team of experts from the California Department of Health Services looked at the number of children in California who were diagnosed with autism each year from 1980 and 1994. After comparing these figures to the number who received the MMR vaccine, they found that the rate of vaccinations rose 14 percent while the rate of autism jumped 600 percent. The team concluded that there could be no link between the vaccine and autism.13

One month later the Institute of Medicine’s Immunization Safety Review Committee, chaired by Marie C. McCormick, M.D., of the Harvard School of Public Health, issued a report saying it examined all studies about the health effects of the MMR vaccine in young children and concluded that there is no connection to autism.14

Vaccine Testing and Regulation

Like all medications, vaccines are rigorously studied prior to being used in humans. In a telephone interview Bruce Gellin, M.D., a pediatrician at Vanderbilt University and executive director of the National Network of Immunization Information, explained the process like this: Pre-clinical tests are done on animals to test safety and effectiveness. If the vaccine is not found to be safe in animals, all testing is stopped. If it is found to be safe in animals, phase I clinical trials test the safety of the vaccine on about 10 to 100 people. If the vaccine is found to have no harmful effects, phase II clinical trials begin to determine how the vaccine is optimally provided, including the correct dose and repetition. Phase III clinical trials determine if the vaccine does what it is supposed to do in a large population (10,000 to 100,000 study participants). After phase III trials, a company can apply for FDA approval. Phase IV trials, also called post-marketing evaluations, study the performance of a vaccine after it has been distributed.

To ensure public safety, the United States government requires additional monitoring of all FDA licensed vaccines and drugs. The Center for Biologics Evaluation and Research (CBER) strictly regulates vaccine products. The CDC and FDA jointly manage the Vaccine Adverse Events Recording System (VAERS). This is a safety surveillance program that collects information about adverse events or side effects that occur after the administration of FDA-approved vaccines. When a report is filed with VAERS, experts will do an investigation to determine the cause.15

Vaccines are quickly removed from the market when adverse events occur. For example, the rotavirus vaccine was discontinued in 1999 because it was found to cause bowel obstruction in 15 infants.

The United States government offers compensation to those injured by vaccines through the National Vaccine Injury Compensation program established by The National Childhood Vaccine Injury Act of 1986.

Part III: New Vaccine Research

Today, advances in science and technology allow researchers to design vaccines that may prevent and/or treat any disease using an immunologic component.

Diabetes Vaccine: William Langridge, Ph.D., a researcher at the Loma Linda University’s Center for Molecular Biology and Gene Therapy, is working to develop a vaccine that could prevent type 1 diabetes in people at high-risk for the disease. Type 1 diabetes results from an autoimmune reaction in which the body destroys beta cells in the pancreas that are needed to produce insulin. Langridge developed one of the first edible potato vaccines that successfully protected laboratory animals from becoming diabetic.16

Also working on a diabetes vaccine are researchers at the University of North Carolina at Chapel Hill. Roland Tisch, Ph.D., created a diabetes vaccine that suppresses the body’s autoimmune response, while leaving the rest of the immune system intact.17 The vaccine was effective in preventing the disease in laboratory mice bred to develop diabetes. His research was published in the February 2001 Journal of Immunology.

Addiction Vaccines: Researchers at Cantab Pharmaceuticals in Cambridge, England, are working to develop a vaccine that will treat cocaine addiction. The vaccine is designed to make the immune system recognize cocaine as a foreign substance. The body then produces antibodies that attach to the drug in the bloodstream, preventing cocaine from reaching the brain, thus blocking the high feeling produced by the cocaine.18

Professionals who treat drug addiction have several concerns about this new treatment. First, the addict will be able to reduce the vaccine’s effectiveness by increasing the amount of cocaine ingested. Second, the body can take up to two months to create the antibodies needed for an effective immune response, which can delay treatment. Finally, because drug dependence is a complex problem involving physiological and psychological issues, experts worry that addicts may switch to alternative drugs to get high.

Thomas Kosten, M.D., a psychiatrist at Yale University, is doing the first clinical trials on this cocaine vaccine (called TA-CD). In phase I clinical trials, he found that the vaccine did not cause major side effects. He is now conducting phase II clinical trials to test the vaccine’s effectiveness on cocaine addicts in an outpatient treatment center.19

AIDS Vaccine: An estimated 5,000 people become infected with HIV each day. AIDS prevention efforts that use behavior modification have been only moderately effective in reducing the spread of HIV. Therefore, researchers around the world have been working to create a vaccine that will prevent HIV infection or slow the progression of the disease. The challenge for scientists is that there are many different strains of the virus, and it mutates often. As of February 2001, there were 35 HIV vaccines undergoing human clinical trials. VaxGen Pharmaceuticals has created one of the first HIV vaccines to be tested on humans. Called GP120, or AIDSVax, the vaccine closely mimics the outer envelope of the virus, creating an immune response when an antibody binds to the vaccine’s coating. To test the efficacy of GP120, about 8,000 people at high-risk for infection in the United States, Canada and Thailand have been given the vaccine and will be monitored over the time.20

The pharmaceutical company Merck & Co has been testing a vaccine in monkeys that appears to prevent the progression of HIV infection. Positive results from their research were presented at a 2001 scientific meeting in Keystone, Colorado, by researchers John Shiver and Emilio Emini. Phase I clinical trials are underway.21

At Duke University, Bart Haynes, M.D. and colleagues are working to develop an HIV vaccine that would be administered as a nasal spray. This vaccine will create a strong immune response in both the mucous membranes (i.e. the genitals where contact with HIV is first made) and the general immune system.22

Norman Letvin, M.D., from the Beth Israel Deaconess Medical Center and Harvard University, is developing a different kind of AIDS vaccine. Letvin’s vaccine is not designed to prevent HIV infection, rather to control the amount of virus in the body, allowing the person to live a longer, healthier life.23 To do this, he uses a specific type of T-cell lymphocyte that kills HIV-infected cells already in the body.

Alzheimer’s Vaccine: Dave Morgan, Ph.D., from the University of South Florida in Tampa, is developing a vaccine to slow and hopefully stop memory loss caused by Alzheimer’s disease. The vaccine, developed by Elan Pharmaceuticals in San Francisco, Calif., was tested on mice bred to develop the disease. The vaccinated mice produced antibodies to beta amyloid - a protein scientists believe accumulates in the brain and causes Alzheimer’s. The vaccine triggers the immune system to remove the amyloid plaques in the brain and may keep them from developing at all. The vaccine is being tested for safety in phase I clinical trials.24, 25

Cancer Vaccines: Genetically engineered vaccines are being used to activate cancer patient’s immune systems to attack and destroy tumors. These are what researchers call therapeutic research. A team at Stanford Medical School led by Lawrence Fong, M.D., created a vaccine called dendritic cell therapy that would help the body’s immune system to recognize cancerous tumor cells as an “enemy” and attack.

The National Cancer Institute is sponsoring about 100 studies of cancer vaccines, the majority of them in patients with melanoma, a type of skin cancer. Donald Morton, M.D., a surgeon from the John Wayne Cancer Institute in Santa Monica, Calif., has developed CancerVax, a vaccine made from melanoma cells that are dying from radiation. Successful trials have led this vaccine to be tested on 1,000 patients with melanoma.26

New Vaccines for Developing Countries

Myron Levine, M.D., director of the Center for Vaccine Research at the University of Maryland School of Medicine, has made substantial contributions to the development of new vaccines. He says, “We would like to see that all vaccines of the future would be given by mouth, on the skin, or through nasal spray.”

The Center for Vaccine Development makes vaccines for children who live in developing countries. Diseases like cholera, typhoid and shigella are virtually non-existent in industrialized nations, but these infections kill millions of children in developing nations. Dr. Levine says, “We are currently working on several projects that include:

* Exploring the widespread use of a live oral cholera vaccine that has already been used by the World Health Organization during a cholera outbreak in Oceania,
* Typhoid vaccine that is in phase II clinical trials,
* Another typhoid vaccine that is just completing phase I clinical trials
* Shigella vaccine that is in phase I clinical trials.

Part IV: Vaccine Shortages

The United States government closely monitors safety and effectiveness of vaccines, but private companies manufacture these products for a profit. As a result, financial issues affecting private pharmaceutical companies can dictate the supply of vaccines while the demand remains constant.

Tetanus: In January 2001, the tetanus vaccine was suddenly in short supply. Until then, two pharmaceutical companies produced the vaccine: Wyeth-Ayerst (a division of American Home Products) and Aventis-Pasteur.

The vaccine business is not profitable because they are expensive to make, research and develop, and the return is very low. The Vaccines for Children Program, established in 1994, helps the CDC distribute vaccines to families that otherwise could not afford them. The program stipulated that the price of vaccines may only rise in accordance with the Consumer Price Index. So when vaccine manufacturers raised the price, the CDC was unable to afford it.27

The tetanus vaccine shortage resulted when Wyeth-Ayerst stopped producing the product after the FDA halted manufacturing at one of the company’s plants in Tennessee. The FDA found problems with the packaging of the vaccine and seized thousands of syringes. In October 2000, the FDA and Wyeth-Ayerst agreed to bring the manufacturing plant up to FDA standards, and the company was fined $30 million. Then in January 2001, Wyeth-Ayerst announced that it was stopping production of tetanus vaccines.28

Flu Vaccine Shortage: The 2000 influenza vaccine was delayed by a month, leaving many Americans at risk early in the flu season. The CDC reported several reasons for the delay, including:29

* The manufacturers of the flu vaccine had difficulty growing one strain of the live virus. As a result the early supply of vaccine was given to those at high risk for flu (older adults, people with suppressed immune systems, and health care workers).
* The FDA found one of the four flu vaccine-manufacturing plants in violation of safety standards and closed it.
* The vaccine was shipped to larger corporations, which delayed the delivery to smaller clinics and physician offices.30

Conclusion: Vaccine use has changed the medical landscape and has contributed to a significant decrease in infectious disease morbidity and mortality in the United States. Experts continue to enhance the quality of vaccines while making great strides to improve access to immunizations for people around the world.

The Global Alliance for Vaccines and Immunization is new organization dedicated to ensuring that all children have equal access to vaccines. The Alliance brings together public health experts from the World Health Organization, UNICEF, the World Bank and others to develop new vaccines against major killers that primarily affect the world’s poorest people. Financial support for GAVI comes from The Global Fund for Children’s Vaccines, which was created with a $750 million grant from The Bill and Melinda Gates Foundation. In time, scientific advances, technology, and financial support hopefully will improve worldwide immunizations. 31

ENDNOTES

1. Lee Dye, "Eating away disease: A scientist hopes specially modified fruits and vegetables can vaccinate the world," ABC News Online, 11 October 2000.

2. Reuters Staff, "Potatoes engineered to carry cholera 'shot,'" 26 Feb 1998.

3. Cat Lazaroff, "Edible Vaccines Carry Flavor of Danger," Environmental News Service, 11 July 2000.

4. Lazaroff, July 2000.

5. Associated Press Staff, "Nasal spray effective at preventing flu," CNN.com http://cnn.com/HEALTH/9907/13/nasal.flu.vaccine.ap, 13 July 1999.

6. Dana Mackenzie, "Vaccinations Without the Ouch," ScienceNOW, 20 September 1999.

7. Interview with Jim Slade, Needle Free Vaccines, http://www.pbs.org/healthweek/featurep1_318.htm, 27 August 1999.

8. Arthur Allen, "Questions for Barbara Loe Fischer on the Costs of Vaccination," The New York Times Magazine, 6 May 2001.

9. Allen, 6 May 2001

10. Bob Edwards, "Profile: Two new studies show no link between hepatitis B vaccine and multiple sclerosis," Morning Edition (NPR), 1 February 2001.

11. Centers for Disease Control and Prevention, National Immunization Program Web site, http://www.cdc.gov/nip/vacsafe/concerns/autism/autism-mmr.htm.

12. Loring Dales, Sandra Jo Hammer, Natalie J. Smith, "Time trends in Autism and in MMR Immunization Coverage in California," JAMA, March 7, 2001, vol 285, No. 9, pg. 1189.

13. Josh Fischman, "Vaccine worries get shot down but parents still fret," US News and World Report, 19 March 2001, pg. 63.

14. Institute of Medicine website, http://www.iom.edu/Imsafety, 24 April 2001.

15. Federal Drug Administration website, http://www.fda.gov/cber/vaccines.htm

16. Staff Writer, "LLU researcher receives major grant to further develop diabetes vaccine," Loma Linda University School of Medicine News, 24 August 2000.

17. Staff Writer, "Vaccine could prevent Type-1 Diabetes," United Press International, 31 January 2001.

18. Charlie Schmidt, "Newsfronts: Science and Technology: Medicine: Cocaine Vaccine," Popular Science, 1 June 1999, pg. 35.

19. Dawn Mackeen, "Immunized against addiction," Salon.com, http://www.salon.com/health/feature/2000/04/26/vaccine, 26 April 2000.

20. Julia Connors, Duke, "Other University Scientists pursue vaccine for HIV," University Wire, 19 March 2001.

21. Michael Waldholz, "Why Merck’s Experimental AIDS vaccine has scientists so excited," The Wall Street Journal, 2 April 2001.

22. Julia Connors, March 2001.

23. Julia Connors, March 2001.

24. Lindsay Peterson, "Hope in sight for fighting alzheimer’s," The Tampa Tribune, 10 April 2001, pg. 3.

25. Gina Kolata, "Separating research from news," The New York Times, 18 July 2000.

26. Daniel Q. Haney, "Vaccines show promise as powerful new cancer treatment," Naples Daily News, 27 August 2000.

27. Amy Standen, 8 March 2001

28. Amy Standen, "Ready for some lockjaw?" Salon.com, http://www.salon.com/tech/feature/2001/03/08/tetanus, 8 March 2001.

29. David Pitt, "Should production problems delay distribution, doctors have to prioritize their patients," Associated Press, 22 June 2000.

30. Mary Ann Elchisak, "Flu shots and influenza vaccine: vaccine shortage," http://pharmacology.about.com, 26 October 2000.

31. Global Alliance for Children’s Vaccines (GAVI) Web site, http://www.vaccinealliance.org.

WEB SITES

Sabin Vaccine Institute -- http://www.sabin.org

Bill and Melinda Gates Children’s Vaccine Program --http://www.childrensvaccine.org/homepage.htm

Boyce Thompson Institute for Plant Research -- http://bti.cornell.edu/

Centers for Disease Control National Vaccine Program Office --http://www.cdc.gov/od/nvpo/default.htm

CDC National Immunization Program -- http://www.cdc.gov/nip/

Food and Drug Administration -- http://www.fda.gov

Global Alliance for Vaccines and Immunizations -- http://www.vaccinealliance.org/

The Dale and Betty Bumpers Vaccine Research Center at the National Institutes of Allergy and Infectious Disease/National Institutes of Health -- http://www.niaid.nih.gov/vrc/default.htm

VaxGen -- http://www.vaxgen.com/

Parents Requesting Open Vaccine Education (PROVE) -- http://www.vaccineinfo.net/

National Vaccine Information Center -- http://www.909shot.com/

World Health Organization Vaccine Initiatives -- http://www.who.int/vaccines

National Network for Immunization Information -- http://www.immunizationinfo.org/index.cfm

Iomai Corporation -- http://www.iomai.com

ENDNOTES

1. Lee Dye, "Eating away disease: A scientist hopes specially modified fruits and vegetables can vaccinate the world," ABC News Online, 11 October 2000.

2. Reuters Staff, "Potatoes engineered to carry cholera 'shot,'" 26 Feb 1998.

3. Cat Lazaroff, "Edible Vaccines Carry Flavor of Danger," Environmental News Service, 11 July 2000.

4. Lazaroff, July 2000.

5. Associated Press Staff, "Nasal spray effective at preventing flu," CNN.com http://cnn.com/HEALTH/9907/13/nasal.flu.vaccine.ap, 13 July 1999.

6. Dana Mackenzie, "Vaccinations Without the Ouch," ScienceNOW, 20 September 1999.

7. Interview with Jim Slade, Needle Free Vaccines, http://www.pbs.org/healthweek/featurep1_318.htm, 27 August 1999.

8. Arthur Allen, "Questions for Barbara Loe Fischer on the Costs of Vaccination," The New York Times Magazine, 6 May 2001.

9. Allen, 6 May 2001

10. Bob Edwards, "Profile: Two new studies show no link between hepatitis B vaccine and multiple sclerosis," Morning Edition (NPR), 1 February 2001.

11. Centers for Disease Control and Prevention, National Immunization Program Web site, http://www.cdc.gov/nip/vacsafe/concerns/autism/autism-mmr.htm.

12. Loring Dales, Sandra Jo Hammer, Natalie J. Smith, "Time trends in Autism and in MMR Immunization Coverage in California," JAMA, March 7, 2001, vol 285, No. 9, pg. 1189.

13. Josh Fischman, "Vaccine worries get shot down but parents still fret," US News and World Report, 19 March 2001, pg. 63.

14. Institute of Medicine website, http://www.iom.edu/Imsafety, 24 April 2001.

15. Federal Drug Administration website, http://www.fda.gov/cber/vaccines.htm

16. Staff Writer, "LLU researcher receives major grant to further develop diabetes vaccine," Loma Linda University School of Medicine News, 24 August 2000.

17. Staff Writer, "Vaccine could prevent Type-1 Diabetes," United Press International, 31 January 2001.

18. Charlie Schmidt, "Newsfronts: Science and Technology: Medicine: Cocaine Vaccine," Popular Science, 1 June 1999, pg. 35.

19. Dawn Mackeen, "Immunized against addiction," Salon.com, http://www.salon.com/health/feature/2000/04/26/vaccine, 26 April 2000.

20. Julia Connors, Duke, "Other University Scientists pursue vaccine for HIV," University Wire, 19 March 2001.

21. Michael Waldholz, "Why Merck’s Experimental AIDS vaccine has scientists so excited," The Wall Street Journal, 2 April 2001.

22. Julia Connors, March 2001.

23. Julia Connors, March 2001.

24. Lindsay Peterson, "Hope in sight for fighting alzheimer’s," The Tampa Tribune, 10 April 2001, pg. 3.

25. Gina Kolata, "Separating research from news," The New York Times, 18 July 2000.

26. Daniel Q. Haney, "Vaccines show promise as powerful new cancer treatment," Naples Daily News, 27 August 2000.

27. Amy Standen, 8 March 2001

28. Amy Standen, "Ready for some lockjaw?" Salon.com, http://www.salon.com/tech/feature/2001/03/08/tetanus, 8 March 2001.

29. David Pitt, "Should production problems delay distribution, doctors have to prioritize their patients," Associated Press, 22 June 2000.

30. Mary Ann Elchisak, "Flu shots and influenza vaccine: vaccine shortage," http://pharmacology.about.com, 26 October 2000.

31. Global Alliance for Children’s Vaccines (GAVI) Web site, http://www.vaccinealliance.org.

WEB SITES

Sabin Vaccine Institute -- http://www.sabin.org

Bill and Melinda Gates Children’s Vaccine Program --http://www.childrensvaccine.org/homepage.htm

Boyce Thompson Institute for Plant Research -- http://bti.cornell.edu/

Centers for Disease Control National Vaccine Program Office --http://www.cdc.gov/od/nvpo/default.htm

CDC National Immunization Program -- http://www.cdc.gov/nip/

Food and Drug Administration -- http://www.fda.gov

Global Alliance for Vaccines and Immunizations -- http://www.vaccinealliance.org/

The Dale and Betty Bumpers Vaccine Research Center at the National Institutes of Allergy and Infectious Disease/National Institutes of Health -- http://www.niaid.nih.gov/vrc/default.htm

VaxGen -- http://www.vaxgen.com/

Parents Requesting Open Vaccine Education (PROVE) -- http://www.vaccineinfo.net/

National Vaccine Information Center -- http://www.909shot.com/

World Health Organization Vaccine Initiatives -- http://www.who.int/vaccines

National Network for Immunization Information -- http://www.immunizationinfo.org/index.cfm

Iomai Corporation -- http://www.iomai.com

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