Saturday, February 25, 2006

Multiple Sclerosis - From Two Relapses A Year To None In 16 Months, GenoMed Trial Results

23 Feb 2006


GenoMed (OTC Pink Sheets GMED), a Next Generation Disease Management company whose business is public health, announced today that its first multiple sclerosis (MS) patient has had no relapses for the past 16 months since beginning GenoMed's protocol in October, 2004.

On October 31, 2005, the patient, a young white woman, wrote:

"Just wanted to share with you that I have just had my first full year with no exacerbations of multiple sclerosis. This has never happened for me since I was diagnosed eight years ago. I have always experienced at the very least two exacerbations each year; Sept/Oct and Dec/Jan without fail, until this last year.

"I have had every reason to have an exacerbation, particularly this year… This has been an incredibly stressful summer and fall. I recently felt extremely tired, as though an exacerbation was imminent, and made sure to get extra rest but never experienced a recurrence. As you well know no one can "will" an exacerbation to go away, and extra rest will not stave it off."

On February 6, 2006 she wrote: "I am feeling great! I haven't had an exacerbation in over 2 years, and have more energy than ever." Said Dr. David Moskowitz, GenoMed's CEO and Chief Medical Officer, "Relapsing, remitting MS is a hard disease to know how to treat because it waxes and wanes so much anyway. This case report is encouraging because the patient had regular relapses every 6 months in the past, and none for the past 16 months. Of course, we need to see if our protocol continues to work in this patient, as well as in more patients. But ours could be one of the more effective treatments for multiple sclerosis yet. It would clearly be one of the least toxic and expensive."

About GenoMed

GenoMed owns patents pending for the use of already existing, safe blood pressure pills to treat many diseases besides high blood pressure, including autoimmune diseases like multiple sclerosis (MS). To enroll in GenoMed's trial, please contact Dr. Moskowitz at dwmoskowitz@genomed.com. GenoMed conducts trials for free, and then charges $800 per patient per year once results have been published.
http://www.genomed.com

Safe Harbor Statement

This press release contains forward looking statements, including those statements pertaining to GenoMed, Inc.'s (the Company's) finances and treatments. The words or phrases "ought to," "should," "could," "may," or similar expressions are intended to identify "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995. Actual results could differ materially from those projected in the forward looking statements as a result of a number of risks and uncertainties, including but not limited to our research and development being subject to scientific, economic, regulatory, governmental, and technological factors. Statements made herein are as of the date of this press release and should not be relied upon as of any subsequent date. Unless otherwise required by applicable law, we specifically disclaim any obligation to update any forward-looking statements to reflect occurrences, developments, unanticipated events or circumstances after the date of such statement.

http://www.genomed.com
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MULTIPLE SCLEROSIS (MS) PATIENTS IMPROVE AFTER STEMCELL USE

Las Vegas, NV 2/21/2006 1:46 AM GMT (TransWorldNews)
Four MS patients, all wheelchair bound, have reported the following results two weeks after the stem cell / placenta implant (the
Implant)

1. Cold feet needing various forms of heating during the night become warm with no need of heating.
2. Substantial improvement or disappearance of spasticity.
3. Being able, while in the wheelchair, to move their legs with relative ease.
4. Urinary frequency markedly reduced, and in one case the use of self catheterization a painful and infection prone procedure, discontinued
5. Initiating or increasing walking distance with the help of a walker.

These results were obtained by Nevada physicians doing the implant procedure in their private offices. Accordingly the use of the implant will be extended to other conditions, besides MS namely Alzheimer's, strokes, juvenile diabetes type I, retinitis pigmentosa (RP), macular degeneration also in children/adolescents with autism and Rett's syndrome. There is also growing interest in using the Implant as an anti-aging/aging-control procedure, placenta having gained already the reputation of being "the Fountain of Youth from the Womb!"

However our main interest now is in MS, and our first objective is to have the placenta implant used in 10+ MS patients, hoping to collect enough data, to enable us to submit to the FDA, the Center of Biological Research (CBER) an Investigational New Drug (IND) application for a biological product.

An interesting proposal had been received from a main TV chain by which they would be interested in a story, where subjects programmed for the implant would be examined by specialized physicians, before and up to three months after the procedure. This proposal would give them also the right to film among others the whole Implant procedure.

STEM CELL PHARMA INC (SCPI)

SCPI is a privately held biotechnology corporation formed May 2005 in Las Vegas. SCPI has acquired from its President, Alfred T. Sapse MD "(Ret) the world wide rights to a proprietary technology titled Amnion Stem Cells, Telomerase Enhanced Placenta Implant (The Implant)." This procedure would enable amnion stem cells/placenta with the potential to differentiate into a wide variety of different organs, including: the heart, liver, and brain, be transferred from the donor, the placenta of the new born, to the recipient in less than three hours. This technique does not need freezing of the cells, and subsequent thawing. Subsequently the multiplication or the increase many fold in the number of stem cells would not be done by culturing them, in a medium often containing rat cells "the feeder" and subject to contamination, as it is being done in many research, but being cultured in the best feeder there is namely in the body of the recipient. The role of enhancing telomerase, an enzyme, which extends the number of multiplications of the stem cells is vital since otherwise these cells multiply only twenty times and die. In this regard a statement by Makki (2005) that the amnion cells lack telomerase activity is incorrect.

The amnion stem cells do have telomerase activity, which activity is increased through a proprietary technique that assures the
multiplication of the telomerase many times over (Suggested reading: Amniotic Fluid Cells and Human Stem Cell Research ? A New Connection by AR Prusa M. Hengstschläger Med. Sci. Monit. 2002: 8(11):RA 253- 257)

Another amazing capability of the amnion cells is in its fetal tissue engineering ie. in building up new tissues. Two (2) cc of
amniotic fluid rich in stem cells, might be able to correct congenital defects if implanted immediately after birth in the body
of a new born with such defects (ibid).

So where do we go from here? We believe that by proceeding with the program of stem cell/placenta implants, as described above, we will be able to bring important new date in the use of amniotic stem cells, which eventually would shorten the time of certain research now in progress and provide new treatments much sooner than anticipated.

For more information please contact:

Alfred T. Sapse MD (ret) c/o
Stem Cell Pharma Inc., Las Vegas, NV
Phone: (702) 734-6814
Fax: (702) 733-9505

Thursday, February 23, 2006

FDA takes a closer look at withdrawn MS drug


Tysabri is on center stage as FDA debates balance between speed and safety
By Aaron Smith, CNNMoney.com staff writer

NEW YORK (CNNMoney.com) - The FDA's balancing act between safety and speed is taking center stage with the multiple sclerosis drug Tysabri.

Two biotechs -- Biogen Idec from Cambridge, Mass. and Elan Corp. from Dublin -- are trying to get their multiple sclerosis drug Tysabri back onto the market. They're losing money on the drug's absence with every passing day, and some patients are clamoring for the drug's return. But two deaths have been attributed to it.

"I think the drug probably returns to market, but it returns in handcuffs," said Bernstein analyst Geoff Porges. Prior to market withdrawal, Porges projected $3 billion in annual sales for Tysabri, but he's lowered that projection to $700 million. Biogen Idec totaled $2.4 billion in 2005 sales for all its products, and Elan totaled $490 million in sales that year.

Biogen Idec (up $1.18 to $48.50, Research) and Elan (down $0.09 to $14.17, Research) put Tysabri on the market in November of 2004, after the FDA approved it as a treatment for MS. The drug was effective in slowing the onslaught of this disabling disease, which attacks the central nervous system, and preventing relapses. Some analysts touted the drug as a potential blockbuster. After the biotechs put Tysabri on the market, they continued to test it for MS, as well as a potential treatment for Crohn's disease, which causes inflammation of the digestive tract, and for rheumatoid arthritis, which causes inflammation of the joints. That's where they ran into trouble.

On Feb. 28, 2005, Biogen Idec and Elan told the FDA they were taking Tysabri off the market and suspending their late-stage clinical trials. Three of the trial patients were diagnosed with progressive multifocal leukoencephalopathy, or PML, a nervous system disorder affecting people with weakened immune systems, including about 10 percent of all AIDS patients, according to the companies. Two of the patients with PML died, one of them during trials and one of them after the trials ended, said Davia Temin of Elan. She said the patients who died were also taking immunosuppresents. The companies said that 3,000 patients participated in clinical trials and another 5,000 patients have used Tysabri.

The drug is still off the market. But on Feb. 15, 2006, nearly a year after the withdrawal, the FDA allowed trials to resume, but only with people who were previously treated in a Tysabri study. FDA advisors will meet on March 7 and 8 to sift through safety and efficacy information and try and figure out what else to do with Tysabri. The advisory committees generally make recommendations to the FDA, but the FDA did not confirm whether the committee would be taking a vote at its upcoming meeting.

In an apparent vote of confidence, Standard & Poor's upgraded Biogen Idec on Wednesday, to BBB from BB-plus, with a stable outlook.

Bringing back Tysabri

Tysabri patients will be making an appearance at the committee meeting to lobby for the drug's market return, said Temin of Elan.

"There has been a huge patient outcry for the drug because it has been proven to be highly effective against what has proven to be a highly intractable disease," said Temin, referring to MS. "We are working very closely with the FDA from the beginning and clearly are putting the safety of patients first, but also want to respond to patient need and desire to getting the drug back on the market."

Jason Kantor, analyst for RBC Capital Markets, said the meeting "ought to have a pretty positive tone to it because it's going to be dominated by a lot of people's testimony about how the drug is beneficial to them and how having the drug off the market has made them worse."

The companies submitted their Tysabri application for the treatment of rheumatoid arthritis and Crohn's disease to the FDA on Sept. 26, 2005. The FDA gave the experimental drug candidate a priority review status. This means that the agency tries to review it within six months, instead of its usual goal of 10 months, because it has life-saving potential and addresses an unmet need. If the FDA meets its own goals for priority review, then a decision on Tysabri would be reached by late March.

The FDA is currently locked in a tug-of-war between safety and speed. The agency has requested, as part of its budget, an additional $6 million to fund Critical Path, the effort to speed up review without sacrificing safety.

The FDA wants to avoid scandals like Vioxx, Merck's arthritis painkiller that was approved by the FDA in 1999 but then pulled off the market in 2004 after a study showed an increase in the risks of heart attacks and strokes in patients who took the drug at least 18 months, prompting nearly 10,000 lawsuits against Merck. Other drugs from the arthritis painkiller class were affected. Pfizer pulled its arthritis painkiller Bextra off the market in 2005, but was allowed to continuing marketing Celebrex with a sterner warning label. All of these drugs were blockbusters, with combined annual sales totaling $8 billion before the troubles emerged.

But critics of the FDA say the agency should not take too long reviewing drugs with life-saving potential, because patients die while waiting for the new treatments to become available. The critics say the FDA will never be able to detect all the risks, because some of them don't become evident in patients for years.

The future of Tysabri

So what's going to happen to Tysabri?

"I think most people believe that this drug is going to come back to market with a restricted [warning] label," said Kantor, the RBC analyst. "But I think there is considerable risk that the FDA will give Tysabri an approvable letter and ask for more data in a clinical trial setting before making it widely available."

Clinical trials are expensive and time-consuming. Amy Brockelman, spokeswoman for Biogen Idec, said the company is setting itself up to resume Tysabri trials in the next few weeks. The next trial would focus on safety for MS patients, said Brockelman, and many of the patients from previous Tysabri trials have shown interest in participating.

Brockelman said the companies might eventually resume studies for Crohn's disease, but are not planning to resume trials for rheumatoid arthritis.

The read more about the FDA's balance between speed and caution, click here. Top of page





Find this article at:
http://money.cnn.com/2006/02/23/news/companies/tysabr
i

Tuesday, February 21, 2006

As makers seek MS drug's return, new question rises

By Denise Gellene
Los Angeles Times

A year ago this month, Anita Louise Smith died from effects of Tysabri, a drug that was supposed to help her cope with multiple sclerosis.

Within days, drugmakers yanked Tysabri off the market, devastating many people with multiple sclerosis who hoped the intravenous treatment would bring them relief.

Now, as makers of the drug prepare to seek approval to put Tysabri back on the market, some prominent neurologists are arguing that Smith should not have been taking it to begin with - because she did not have MS.

Smith's case dramatizes a new debate over how multiple-sclerosis drugs are tested: In recent years, drug companies have been trying out medicines on people with mild symptoms or none at all, several experts say - including some who, like Smith, might not have the disease. Critics say these trials broadened the market for MS drugs but put at risk some patients who do not need powerful new medicines.

Smith was taking the drug as part of a clinical trial that regulators had required when they granted Tysabri fast-track approval. Most of the 1,171 patients in her trial suffered no disabilities, according to Food and Drug Administration documents.

"People with no active disease - in other words, people who are doing fine - shouldn't be given an experimental drug with unknown risks," said Lawrence Steinman, a Stanford University neurology professor and a co-inventor of Tysabri who previously has spoken out about the drug's dangers.

Last week, Steinman and another Stanford neurologist, Annette Langer-Gould, urged the FDA to tighten criteria for selecting patients in MS drug trials.

"We are concerned that not only were patients put at risk by Tysabri, but we feel that the risk was absolutely unnecessary to assume," they wrote in an e-mail to the agency.

Biogen Idec Inc. and Elan Pharmaceuticals Inc. hope to win government permission as soon as next month to resume sales of Tysabri. They say that it is an effective treatment for multiple sclerosis and that carefully selecting and monitoring patients can manage the risks.

Biogen Idec spokeswoman Amy Brockelman said privacy requirements prevented the company from commenting on Smith's case. But all aspects of the Tysabri clinical trials were approved by the FDA and by oversight boards at the medical centers where the studies were conducted, she said.

FDA spokeswoman Susan Cruzan said the agency would not comment on matters surrounding Tysabri before an advisory panel meets March 7 to discuss the drug's possible return to the market.

Experts see the drug as a potential boon in the battle against multiple sclerosis, a disease in which errant white blood cells destroy the coating that protects cells in the brain and spinal cord. About 400,000 people in the United States have the disease.

For most patients, the disease is marked by flare-ups and remissions. Many experience only minor symptoms, such as numbness or tingling. But while the disease is seldom fatal, about half of MS patients become disabled - such as comedian Richard Pryor, who could not speak, swallow, or get out of bed unassisted in the years before he died late last year.

http://www.philly.com/mld/philly/living/health/13920991.htm?source=rss&channel=philly_health

Sunday, February 19, 2006

Breakthrough for MS

- Multiple sclerosis can leave its victims unable to move and in constant pain. It's an autoimmune disease that wrecks havoc on the central nervous system. In some cases, no treatment works. Now, a new therapy stops the disease's progression and gets patients out of bed and back on their feet.

On her 40th birthday, Andra Litman was taken down a path unthinkable. "Unless you're in this body, I don't know how you can begin to imagine," she says.

Doctors diagnosed this artist, attorney, and mother of two with multiple sclerosis, a disease that left her unable to even turn over in bed. Then she started a new treatment. She was out of a wheelchair and on her feet in one month.

Neurologist Olaf Stuve, M.D., Ph.D., says the cancer drug rituximab (Rituxan) is the first treatment to target the B cells in patients with MS, and it could be the first effective treatment for patients when nothing else works.

"The response to the Rituxan in those patients were really dramatic, in terms of not only stopping disease progression, but really helping the patient to recover some of the neurological function," Dr. Stuve, of UT Southwestern Medical Center in Dallas, tells Ivanhoe.

Instead of a daily or weekly injection, rituximab requires two infusions every six months. White spots, or lesions on a patient's brain before treatment, are hallmarks of MS. After treatment, they are gone.

Dr. Stuve says, "I think it will be a very effective therapy and probably more effective than what we have available at this time."

Litman says, "The first thought every morning when I woke up for four years was, 'Is it a shot night?'" Now, she can tune her thoughts to what matters most.

Since rituximab only targets one aspect of the immune system, it poses fewer side effects than standard treatments. Dr. Stuve is just beginning a study on using rituximab to treat primary-progressive MS (PPMS), a specific form that affects 10 percent of patients and for which there are no effective treatments.

If you would like more information, please contact:

Aline McKenzie
Office of News and Communications
UT Southwestern Medical Center
5323 Harry Hines Blvd.
Dallas, TX 75390-9060
(214) 648-3404
aline.mckenzie@utsouthwestern.edu
http://www.utsouthwestern.edu

http://abclocal.go.com/kfsn/story?section=health&id=3836145

Saturday, February 18, 2006

Tysabri, an MS Drug with Potentially Deadly Side-Effects, Gets FDA Approval for Resumption of Clinical Testing

Date Published: Saturday, February 18th, 2006
http://www.newsinferno.com/archives/856

By Steven DiJoseph

When Mark Twain said, “The reports of my death have been greatly exaggerated,” he could have been writing the opening sentence of an article about Tysabri, the MS drug with potentially deadly side-effects that, like the proverbial Phoenix, has risen from the ashes. Many experts have been left shaking their heads as this modern-day “cat with nine lives” simply refuses to die.

Although the hastily approved drug was pulled from the market in 2005, after only four months, following reports of its involvement in the deaths of at least two people, the effort to have Tysabri re-approved began almost immediately.

The first seed that was planted to “explain” why Tysabri was not the real culprit in the fatal and near fatal consequences was a report that the adverse reactions may have been due to an interaction with another Biogen Idec (“Biogen”) product, Avonex that led to a build-up and overdose of the active ingredient in the mediation.

An interaction of Tysabri and Avonex, an older MS drug “essentially leads to almost double the intended Tysabri concentration after only 20 weeks,'’ NCB Stockbrokers analyst Orla Hartford said in a note to investors in July. “Patients on Tysabri alone did not accumulate the drug.'’

It was immediately presumed that this revelation would “form a central part of the case made to the FDA for Tysabri’s relaunch,'’ she said. Hartford, who analyzed data submitted to the U.S. Food and Drug Administration during the approval process, expected the drug to be reintroduced in 2006.

Elan Corp. PLC (“Elan”) and Biogen, the manufacturers, immediately went to work reviewing medical records of patients who had taken the drug in order to find a way to justify seeking re-introduction of the drug from the FDA.

As we previously reported on July 1, 2005, despite the fact that Tysabri had been linked to five cases of a rare and often fatal brain disease, Elan (of Ireland) and Biogen (of Massachusetts) were simply unwilling to give up their quest to bring the drug to market and keep it there.

The two drug makers announced a third-phase trial had produced positive results with respect to the treatment of Crohn’s disease. The trial involved 510 men suffering from Crohn’s and produced a reduction in symptoms within 12 weeks of treatment.

Tysabri, which is designed to suppress the symptoms of multiple sclerosis and Crohn’s disease,

has traveled a very rocky road from the beginning. Shortly after its withdrawal from the market, the FDA was informed by Biogen that a fifth person had developed a rare brain disease known as progressive multifocal leukoencephalopathy (PML) after being treated with the drug.

Biogen and Elan, its development partner, had hoped to return the drug to the market despite three previously confirmed cases of PML (with two deaths) as well as a fourth unconfirmed case. Sales of the drug were suspended on February 28, 2005.

Just before the report of the fifth suspected PML case surfaced in mid-June, Biogen was hinting at a strategy for bringing the drug back to the market that included testing all patients for the virus that causes PML and stop treatment with Tysabri in time to allow the patients to recover.

Many experts, however, remained skeptical about the future of the drug and were not sure at what point additional cases of PML will prove to be an insurmountable obstacle to that plan. The report that a drug interaction, and not Tysabri alone, may have been the problem merely added to the controversy.

By July, Elan’s stock value had suffered repeatedly (since the February 28 withdrawal) and, at one point, its shares were trading at only about 25% of their value before Tysabri was pulled from the U.S. market.

When we interviewed Jerrold S. Parker, a partner in the New York personal injury law firm of Parker & Waichman that represents the estate of one of the patients who died from a confirmed case of PML while taking Tysabri, he stated: “It is simply amazing to watch Biogen and Elan insist on placing profits above safety. Clearly, they will do anything possible to recover their investment and turn a profit on this questionable drug. This is a drug that simply refuses to die.”

Shortly after that interview, Parker & Waichman commenced an action against Biogen and Elan for the wrongful death of a 46-year-old wife and mother of two.

In February 2000, Anita Smith was diagnosed with multiple sclerosis (MS). By April 2002, she was enrolled in a clinical trial involving the MS drug, Tysabri along with 1,200 other patients.

In November 2004, while Anita Smith’s health was rapidly deteriorating and she was experiencing severe neurological problems, Tysabri gained a coveted “fast-track” approval from the FDA.

Anita Smith took her last IV infusion of Tysabri in January 2005. On February 24, 2005 she died of a rare, and often fatal, brain infection known as PML; the same disease that killed other Tysabri patients.

Four days later, Tysabri sales were halted. Respected scientists and other experts, who had warned of such potential consequences associated with the powerful immunosuppressant, were not surprised.

A careful review of the extensive 64-page (315-paragraph) complaint with 14 separate causes of action revealed a number of interesting facts and allegations:

A second MS drug, Avonex, also manufactured by Biogen was used jointly with Tysabri as an MS treatment during clinical trials. Anita Smith’s neurologist was already treating her with Avonex since February 2000.

Anita Smith’s neurologist was paid (as an agent, servant, or employee) by Biogen and Elan as an “Investigator” in their clinical trial of Tysabri.

While taking Tysabri and Avonex in the clinical trial, Anita Smith and others developed opportunistic infections including Progressive Multifocal Leukoencephalopathy (“PML”).

PML is a typically fatal brain disease caused by the immunosuppressive effects of Tysabri or the immunosuppressive effects of Tysabri in combination with Avonex.

Smith’s treatment was comprised of 30 IV infusions beginning on April 12, 2002 and ending in January 2005. Tysabri had received fast-track FDA approval in November 2004, the same month Smith began to suffer severe neurological problems.

She was hospitalized on February 12, 2005 and diagnosed with PML. Smith died on February 24, 2005. Tysabri sales were suspended by defendants on February 28, 2005. An autopsy (participated in by defendants) confirmed that Anita Smith died of PML.

An explanation of the mechanism of the infection is set forth in detail as follows:
On March 2, 2005, Forbes published an article about PML under the headline, “The Virus That Took Down Tysabri,” which described the virus’s latent virulence as follows:

The JC virus, discovered in 1971 and named with the initials of the patient in whom it was found, is present in almost everyone but only destroys the brain when somethings damages the immune system and allows the virus to run rampant.” […]

As far back as 1992, based on animal studies and other in vitro experiments, scientists who developed Tysabri had concluded that it was far too dangerous to use in humans.

By suppressing the immune system, Tysabri allows the JC virus, ordinarily latent in a patient’s kidney, to travel to the brain via the bloodstream, where it begins uncontrolled replication.

Based on all of the available data, many experts believe Biogen and Elan should have conducted long-term studies before ever testing Tysabri on human subjects. It is alleged that at no time did either company disclose to the participants in the clinical trials of Tysabri that literature in professional journals questioned the use and/or safety of the drug in humans.

On March 1, 2005, The New York Times published an article in which a leading expert on Tysabri who participated in its original development stated that no one should have been surprised that patients being treated with Tysabri would contract PML. In this regard,the article stated, in relevant part:

“Lawrence Steinman, a professor of neurology and head of immunology at Stanford, said the F.D.A. should not have approved the drug on the basis of only one year’s data. He said the risk of serious infections like P.M.L. was ‘unfortunately logical’ given that Tysabri works by interfering with the immune system.

“I’m shocked that it happened so soon, but I knew it was going to happen sooner or later,” said Professor Steinman, who participated in an early animal study that led to the development of Tysabri. Dr. Steinman is a co-founder and director of Bayhill Therapeutics, a company developing competing drugs for multiple sclerosis.

“Dr. Steinman said he had expressed his apprehensions about the drug in speeches and in an article in the journal Science in July and had been asked by Biogen executives to tone down criticism of the drug.”

On March 9, 2004, the Los Angeles Times published an article providing specifics with respect to the infection rate and adding that FDA officials lacked sufficient information about Tysabri’s long-term effects. That article stated, in relevant part:

“In hundreds of pages of documents that offered the first detailed look at the FDA’s handling of the drug, reviewers noted that Tysabri appeared more effective than existing drugs, reducing relapses in patients by 66%, based on one year’s data. The reviewers said it was “reasonably likely” that the drug would provide long-term benefits.

“Nonetheless, the agency’s drug reviewers acknowledged they were unsure about Tysabri’s long-term effects.

“‘The clinical meaningfulness of a decrease in the incidence of relapses at one year is uncertain,’ the reviewers wrote.

“FDA reviewers found that Tysabri had an acceptable safety profile, though they noted that health risks ‘beyond one year are not known.’

“Infections, including urinary and respiratory, were seen with Tysabri, but they were ‘generally routine and did not have a complicated course,’ the reviewers said.

“Stanford University professor Dr. Lawrence Steinman, an MS specialist, had warned there was a clear risk of infection for patients taking such drugs, because they tend to suppress the body’s immune system.

“Steinman had helped discover the active agents in the drug, but later became concerned about potential side effects, and is working on a competing drug. He noted that the infection rate of Tysabri patients in one trial was 2.1%, compared with 1.3% in the placebo group.

“‘There were hints of an increase in the infection rate,’ said Steinman. ‘The FDA should have dug deeper.’”

While MS patients and parents of children with MS were concerned that what appeared to be a promising medication may never make it back on the market, many experts in the field of pharmaceutical development regard Tysabri as a dangerous drug that never should have been approved by the FDA in the first place.

There is also the claim that Tysabri should not have been used in human trials before thorough long-term studies were conducted.

Most of all, however, there appears to have been ample evidence in the form of test data and opinions from highly qualified and credible experts that this drug posed a serious risk of the very injuries (and deaths) that ultimately occurred.

Certainly, PML was always a possible risk due to the immunosuppressive quality of the drug. This factor made the combination therapy of two such drugs (Tysabri and Avonex) problematic and worthy of serious consideration (and appropriate warnings) before it was routinely prescribed to patients in the clinical trial.

For several years now there has been a growing concern among independent experts that the pre-approval process used to determine the suitability of a new drug for marketing is getting worse instead of better.

Since the late 1990s, there has been a dramatic increase in the number of drugs which have had to be withdrawn from the market. The institution of an industry-funded a “fast track” drug approval process has lead to inadequately tested drugs being rushed to market and the need for more and more serious (“black box”) warnings.

Many drugs which have caused widespread injuries or deaths have been unceremoniously pulled from the market not long after their release. Some of the more recent “failures” in the longevity department are: Tysabri – 4 months; Lotronex – 9 months; Duract – 11 months; Posicor – 12 months; Redux – 17 months ; Raplon – 19 months; Raxar – 23 months; Baycol – 27 months; Rezulin – 38 months; and Baycol – 50 months.

One in five new drugs has serious side effects that do not show up until well after FDA approval. This often results from what many experts see as two serious flaws in the current “fast track” or “accelerated” approval process, namely, the lack of longitudinal (long-term) testing and the use of test groups which are far too small to represent an accurate sampling of the true range of patients who are likely to take the drugs being tested.

Significantly, in a high percentage of situations, problems develop either; (1) after patients have taken a drug for greater periods of time than the test groups, or (2) in segments of the population which were never included in the test groups at all or, at least not in a sufficient representative sample size.

Moreover, today’s drugs are being marketed without dosing charts or information with respect to the well-known fact that each person will metabolize a drug differently.

The pharmaceutical industry has also largely ignored the developing science with respect to “pharmacogenetics” which is the branch of genetics that studies the variations in responses to drugs based on individual genes.

These genetically determined differences in reactions to a given drug cannot be properly studied or determined when small test groups are exposed to a drug for a very short test period.

The Food and Drug Administration (FDA) has also placed itself in a compromising position by accepting huge sums of money from the pharmaceutical industry to fund the agency’s Office of New Drugs which is now expected to “fast-track” drugs to market.

The pharmaceutical industry now funds more than 50% of the FDA’s fast-track approval process for branded drugs, and overall, there are some 2,500 employees assigned to review an average of about 150 New Drug Applications (NDA) a year. The new drug evaluation and monitoring budget was about $400 million last year.

No such funding is given to the FDA for post-approval monitoring of adverse reactions and side-effects by the Office of Drug Safety which only has about 112 employees.

Fast-track approvals, which are usually based on short-term testing of small test groups, have had disastrous results when used for drugs which are specifically designed for long-term or lifetime use by large segments of the population.

Experts fear the pre-approval lack of long-term studies and the use of relatively small test groups can only lead to significant post-approval problems when less common or delayed side-effects become apparent.

At this time, however, it appears that the FDA is unwilling to admit it may have a problem when it comes to approving drugs based on insufficient clinical tests.

According to the director of the FDA’s Office of New Drugs, Dr. John Jenkins, the agency has no plans to act on suggestions from several experts that it request drug manufacturers to conduct larger clinical studies in the pre-approval process in order to detect serious, but less common, side-effects.

Jenkins claimed there might be “unintended consequences to what sounds like an easy, good idea.” One example would be to delay access to new therapies.

Many critics of the current process disagree. If a new drug makes it to market through fast-track approval only to be pulled from the market almost immediately due to the emergence of side-effects that were not detected because of inadequacies in the clinical study process, what purpose was served by rushing the approval in the first place?

Despite all of the concern over the fast-track approval process in general and the approval of Tysabri in particular, the FDA has announced that it has granted permission for the clinical studies of the drug to continue.

In its announcement, the FDA stated that it had “removed the clinical hold” on studies of Tysabri. “This will allow clinical trials to go forward.”

“In February 2005 Biogen-IDEC had announced suspension of marketing and clinical trials after three patients developed progressive multifocal leukoencephalopathy (PML), a frequently fatal infection of the brain, two following treatment with natalizumab for MS, and one patient being treated for Crohn’s Disease. Two of these cases were fatal.”

The removal of the clinical hold allows patients with MS who were previously treated with the drug under an investigational (IND) study to resume treatment “in an IND study following discussion with their physicians about the potential risks and potential benefits of treatment.”

Remarkably, the FDA stated that, “Although this treatment has been shown to have benefit in patients with relapsing-remitting MS, concern about the risk of PML associated with use of Tysabri remains.”

While the “drug is not being placed back on the market at this time,” the FDA has scheduled an Advisory Committee Meeting on March 7 and 8, 2006 to discuss an application for Tysabri for use in treating patients with relapsing forms of multiple sclerosis. “Aspects for discussion include the risks associated with the drug, its efficacy in the treatment of multiple sclerosis relapses and disability, its possible return to the marketplace, and its proposed risk management plan(s).”

In a Q & A with respect to the lifting of the “clinical hold,” the FDA stated that it was taking this action because an “extensive re-examination that Biogen and Elan undertook on all patients who had received natalizumab in clinical studies” revealed, “No additional cases of PML.” In addition, “Biogen has proposed a resumption of natalizumab administration under an IND study with very specific plans for close monitoring of patients.”

Although not mentioned in the body of the FDA release, the following statement was included at the end of the answer to the question: “Will Tysabri be available to all patients?” “Biogen has not proposed to administer the drug to anyone who had not previously been receiving it under an IND study. Biogen has submitted an application to FDA to resume marketing the drug for more widespread use. That application has a due date for a decision by FDA in late March 2006.”

To further justify what many experts see as an imprudent decision by the FDA, the agency stated that, while it “remains very concerned about the potential for PML associated with natalizumab use” the currently available information is “not adequate to clearly define the level of risk or the exact circumstances when this risk occurs.”

In addition, the FDA stated that “the existing efficacy data with natalizumab indicate this is a very effective product and multiple sclerosis is a devastating neurologic disease.”

Although the logic behind further testing makes sense to some experts, there are some that believe the drug should never have been approved in the first place.

As reported in HealthDay News (2/17): “A multiple sclerosis drug pulled from the market early last year due to safety concerns was initially approved too quickly and probably should not go back on the market, at least not without more data, according to an expert writing in this week’s British Medical Journal.”

The author believes Tysabri was approved too quickly in the first place. According to Dr. Abhijit Chaudhuri, a consultant neurologist for the Essex Centre for Neurological Sciences at Oldchurch Hospital, Romford, Essex, in England: “The rate at which Tysabri was first tracked is absolutely unacceptable for a condition like multiple sclerosis, which can last for 30 years. They did not even look into the side effects and this is unbelievable. It’s a major failing.”

Dr. Chaudhuri agrees with the need for further study: “If a study is being conducted with ethical approval and physicians and participants are well aware of the risks, I have nothing to disagree about. Any scientific study where use of new product is closely monitored should go ahead.”

He was quick to point out, however, that he disapproves of the initial approval process for the drug.

“According to Chaudhuri, the FDA approved Tysabri only on the basis of short-term results from two unpublished trials, and before final data were available.” (HealthDay News 2/17)

“Based on what we’ve seen so far, there is no evidence to suggest that this is very effective for MS,” he said. “We’re talking about a condition that affects young people fairly early in life and which lasts for 30 to 40 years, so it’s a lifelong disease. Before you start using that, you must have convincing and compelling evidence that long-term disability is significantly reduced, at no cost for side effects. And I don’t think we have that kind of information.”

While there are still significant hurdles for Tysabri to overcome before gaining approval for re-introduction to the market, critics of the FDA drug approval process and of the agency’s close ties to the pharmaceutical industry are already predicting that the drug could survive the advisory panel review in March and be the subject of a new application for approval in the not too distant future.

When we asked several litigation attorneys familiar with pharmaceutical products to comment on the Tysabri saga, they were unanimous in their skepticism concerning the FDA’s ability to protect the public from harmful drugs given the current state of the approval process. Jerrold Parker summed it up like this: “I certainly wouldn’t bet against Tysabri making it back to the market. If the FDA’s track record over the past several years tells us anything, it tells us that, with respect to the drug approval process, the bottom line usually wins out over concerns for the health and safety of the public.”

(Sources: FDA Press Release and Q & A; British Medical Journal; HealthDay News; The New York Times, Los Angeles Times; Complaint in Smith v. Biogen, et al.; and Newsinferno.com Archives)

This entry was posted on Saturday, February 18th, 2006 at 6:49 am and is filed under Legal News, Drug Side Effects, Health Concerns.

Friday, February 17, 2006

FDA Extends Tysabri Meeting By One Day, Removes Clinical Hold

FDA is adding another day to the advisory committee review of Biogen Idec/Elan's Tysabri in conjunction with its decision to remove the clinical hold on the multiple sclerosis therapy.

Tysabri will now be reviewed March 7-8 by FDA's Peripheral & Central Nervous System Drugs Advisory Committee. The March 8 date was added because of the large number of patients that requested to testify.
The agency's removal of clinical hold could pave the way for re-entry of Tysabri to the marketplace.
Patients who had been receiving Tysabri within an IND study at the time of the product's suspension in February 2005 will be eligible to participate in the open-label, multi-center safety extension study that Biogen and Elan plan to initiate in the coming weeks.
The IND study has "very specific plans for close monitoring of patients," FDA says in a Q&A document posted on its website Feb. 15. "Biogen has not proposed to administer the drug to anyone who had not previously been receiving it under an IND study," the agency notes.
FDA based its decision on the safety evaluation conducted by the companies of more than 3,000 patients who had received natalizumab in clinical studies under an IND. The evaluation found no additional cases of progressive multifocal leukoencephalopathy.
The safety extension study will give FDA a test run for any risk management programs that would be implemented if Tysabri is brought back to the market.
FDA says it remains "very concerned about the potential for PML associated with natalizumab," but notes that it cannot determine the level of risk based on available data.
Furthermore, "existing efficacy data with natalizumab indicate this is a very effective product and multiple sclerosis is a devastating neurologic disease," the agency states.
As a result, "if a study is done in a manner that provides as much safety monitoring as feasible, it is reasonable to resume studying this product under IND to obtain more safety-related information that may permit us to begin to better understand how large or small the true risks associated with natalizumab are," FDA concludes.
The sBLA for Tysabri, filed in September 2005, was granted priority review and has a late-March user fee date.
To watch a webcast of this meeting, click the button below. To arrange for live videoconferencing, or to order videotapes & DVDs, email FDATV@elsevier.com or call 800-627-8171.
Posted: Friday, February 17, 2006

http://www.fdaadvisorycommittee.com/FDC/AdvisoryCommittee/Committees/Peripheral+and+Central+Nervous+System+Drugs/030706_tysabri/TysabriX.htm

Human Exposure To Aluminium And Multiple Sclerosis Link, Keele University

17 Feb 2006

Scientists at Keele University in Staffordshire have discovered the first evidence of a link between human exposure to aluminium and multiple sclerosis.

Their research has demonstrated very high (up to 40 times the control level) urinary excretion of aluminium in MS, particularly so in the relapsing-remitting form of the disease. Urinary excretion of iron was also significantly elevated in MS and particularly so in the secondary progressive form of the disease.

Urinary excretion of silicon, the ‘natural' antagonist to the potential toxicity of aluminium, was decreased in MS and particularly so in secondary progressive form of the disease.

The research suggests that individuals with MS have a higher body burden of aluminium and that their urinary excretion of aluminium is linked to changes taking place during the relapsing-remitting stage of the disease.

Dr Christopher Exley, Birchall Centre for Inorganic Chemistry and Materials Science, Lennard-Jones Laboratories, Keele University, Staffordshire, said: “If, as is currently believed, MS is a disorder resulting from the interplay between the environment and susceptibility genes then our observation of elevated excretion of iron may be indicative of the latter, while elevated excretion of aluminium suggests that exposure to aluminium may be the hitherto unrecognised environmental factor in MS.”

Other researchers involved in the study were: Godwin Mamutse(2), Olga Korchazhkina(3), Eleanor Pye(2), Stanislav Strekopytov(1), Anthony Polwart(4), Clive Hawkins(2).

(2) - Department of Neurology, University Hospital of North Staffordshire, Keele University, Staffordshire, UK.

(3) - Institute for Science and Technology in Medicine, Keele University, Staffordshire, UK.

(4) - School of Life Sciences, Huxley Building, Keele University, Staffordshire, UK.

KEELE UNIVERSITY
Keele
Staffordshire
ST5 5BG
UK
http://www.keele.ac.uk
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Tysabri multiple sclerosis clinical trial hold lifted by US FDA

http://www.pharmabiz.com/article/detnews.asp?articleid=31967
Thursday, February 16, 2006 16:00 IST
Cambridge

The Food and Drug Administration have removed the hold on clinical trial dosing of Tysabri (natalizumab) in multiple sclerosis (MS) in the US.

Biogen Idec and Elan Corporation plc can now resume clinical trial dosing in MS.

The two companies expect to begin an open label, multi-centre safety extension study of Tysabri monotherapy in the US and internationally in the coming weeks.

Biogen Idec and Elan had previously voluntarily suspended Tysabri from the US market and all ongoing clinical trials based on reports of progressive multifocal leukoencephalopathy (PML), a rare and potentially fatal, demyelinating disease of the central nervous system. Biogen Idec and Elan completed a comprehensive safety evaluation of more than 3,000 Tysabri patients in collaboration with leading experts in PML and MS. The results of the safety evaluation yielded no new confirmed cases of PML beyond the three previously reported, claims the company release.

On September 26, 2005 the companies submitted a supplemental biologics license application to the US FDA. Subsequently, the FDA designated Tysabri for priority review. The FDA grants priority review status to products that are considered to be potentially significant therapeutic advancements over existing therapies that address an unmet medical need.

Based on the FDA's designation of priority review for Tysabri in MS, the companies anticipate action by the agency approximately six months from the submission date, or by late March 2006. The FDA's Peripheral and Central Nervous System Drugs Advisory Committee will review Tysabri on March 7 and 8, 2006.

Thursday, February 16, 2006

FDA says Tysabri can be given to some MS patients

Last Update: 3:20 PM ET Feb 15, 2006

(Updates with new information about FDA considering lifting of other clinical trials involving proposed MS drug by GlaxoSmithKline in seventh paragraph.)

WASHINGTON (MarketWatch) -- The Food and Drug Administration said Wednesday that Biogen Idec Inc. (BIIB) and Elan Corp. (ELN) can begin giving their drug Tysabri to some patients with multiple sclerosis.
The FDA said the companies can make the drug available to patients who were receiving the drug as part of preclinical studies.

The companies voluntarily removed Tysabri from the U.S. market last February after two patients developed a rare brain disorder and one died. A third patient was later discovered to have the disorder, known as progressive multifocal leukoencephalopathy, or PML, in studies of the drug for Crohn's disease, an intestinal illness. No additional cases of the disorder have been found.

On March 7, the FDA will convene an outside panel of medical experts to make recommendations about whether Tysabri should be allowed to return to the broader market. The FDA is expected to make a final decision by the end of March.
In a posting to its Web site on Wednesday, the FDA said it "remains very concerned about the potential for PML" associated with Tysabri. "However, the currently available information are not adequate to clearly define the level of risk or the exact circumstances when this risk occurs."

The FDA also said existing data on Tysabri show the drug "is a very effective product and multiple sclerosis is a very devastating disease." The FDA also said it would consider lifting holds on other MS clinical trials involving drug compounds similar to Tysabri if requested by drug makers. The FDA placed a hold on the trials, including one involving a proposed drug by GlaxoSmithKline PLC (GSK), after Tysabri was removed from the market.

If Tysabri were allowed to be returned to the market, it will likely contain new warnings about the possibility of PML and restrictions. The FDA first approved the drug in November 2004 to treat MS, a progressive disease that affects the spinal cord and brain and involves damage to nerves that control muscles and vision. The drug was on the market only for a short time before being pulled last year.

Biogen and Elan filed for permission to return Tysabri to the market in September. The FDA granted so-called priority review status to the application, which is usually reserved for drugs the agency deems would be a "significant improvement" compared to existing treatments if the product were to be approved. It cuts about four months off of the typical 10-month review period for a drug.
-Contact: 201-938-5400

http://www.marketwatch.com/News/Story/Story.aspx?guid=%7B9AFEEFFB%2DCD14%2D445C%2D83B4%2DF354ABBC0E0A%7D&siteid=google&dist=

Tuesday, February 14, 2006

XANTHUS' SYMADEX™ SHOWS REMYELINATION IN MULTIPLE SCLEROSIS ANIMAL MODEL

XANTHUS' SYMADEX™ SHOWS REMYELINATION IN MULTIPLE SCLEROSIS ANIMAL MODEL

-Results Presented at the International Workshop on Myelin Imaging in Vancouver-

CAMBRIDGE , Mass. , - February 13, 2006 - Xanthus Life Sciences, Inc., today announced that data from a study conducted with a Multiple Sclerosis (MS) animal model demonstrated that Symadex™ permitted remyelination by prevention of inflammatory cell infiltration. Stephen J. Karlik, Ph.D., Professor of Diagnostic Radiology at the University of Western Ontario, London, Ontario presented the research findings on February 10, 2006 at the International Workshop on Myelin Imaging, in Vancouver .

Dr. Karlik is widely recognized for investigating potential new therapies for MS in a specialized animal model of human MS that incorporates both inflammatory and demyelinating properties. Symadex was found to produce remyelination in the study even after 40 days of inflammatory insult by preventing the infiltration of autoreactive cells into the central nervous system. Treatment proved to be effective in both the acute and c hronic presentations of disease.

“The early results from this study showed that the animals in the study, which were paralyzed due to neurological impairment, were able to recover and regain their mobility after treatment with Symadex,” commented Dr. Karlik.

“Symadex is now in Phase 2 trials in oncology and the positive results of this animal model study show the candidate’s potential for treating MS and provide the support needed to advance Symadex towards human trials for MS,” said Michael A. Boss, PhD. Chief Business Officer at Xanthus.

About Symadex™

Symadex (formerly C-1311) is a next-generation investigational drug that has shown a potentially novel, targeted mechanism of action in studies of cancer and autoimmune disease. Symadex was developed to deliver efficacy comparable to the anthracenediones (e.g., Novantrone® ( mitoxantrone)), but with a molecular scaffold intended to reduce the cardio- and hemato-toxicities known to be associated with these active drugs. Additionally, in previous preclinical studies, Symadex has shown early evidence of both oral activity and efficacy in various models of acquired drug resistance and autoimmune disease. The Company is conducting Phase 2 clinical trials with Symadex in several tumor indications and is also exploring the use of Symadex for the treatment of a number of autoimmune diseases, such as Multiple Sclerosis.

About Multiple Sclerosis

Multiple Sclerosis (MS) is a chronic, unpredictable disease of the central nervous system that, according to the National MS Society, affects approximately 400,000 people in the United States and approximately 2.5 million people worldwide. It is a disease typically of young adults, mostly women, with onset typically between 20 and 50 years of age. Each hour someone is newly diagnosed. MS symptoms may include vision problems, loss of balance, numbness, difficulty walking and even complete paralysis.

About Xanthus Life Sciences, Inc.

Xanthus Life Sciences, Inc. is developing a portfolio of novel, clinical-stage, small-molecule oncology drugs through a management team whose accomplished track record encompasses all aspects of drug development, from discovery through regulatory approval and commercialization. The Company is applying its expertise both to advance its current pipeline and expand it into indications of unmet medical need beyond oncology.

Xanthus is headquartered in Cambridge, Massachusetts with an additional facility in Montreal, Quebec. More information is available at www.xanthus.com.

This press release contains forward-looking statements concerning Xanthus that involve a number of risks and uncertainties. For this purpose, any statements contained herein that are not statements of historical fact may be deemed to be forward-looking statements. Without limiting the foregoing, the words, "believes," "anticipates," "plans," "expects," "estimates," "intends," "should," "could," "will," "may," and similar expressions are intended to identify forward-looking statements. There are a number of important factors that could cause Xanthus’ actual results to differ materially from those indicated by such forward-looking statements, including risks as to whether results obtained in early clinical studies or in preclinical studies such as the studies referred to above will be indicative of results obtained in future clinical trials or warrant additional trials; whether products based on Xanthus’ technology will advance through the clinical trial process and receive approval from the United States Food and Drug Administration or equivalent foreign regulatory agencies; whether the company will have the cash resources to develop and commercialize its products; and whether the patent and patent applications owned or licensed by Xanthus will protect the Company’s technology and prevent others from infringing it. Xanthus disclaims any intention or obligation to update any forward-looking statements.

Contacts:

Kari Watson, MacDougall Biomedical Communications, Inc. – kwatson@macbiocom.com or (508) 647-0209

John A. McCarthy, Jr., Senior Vice President & CFO, Xanthus Life Sciences, Inc. – john.mccarthy@xanthus.com or (617) 225-0522, x 125

http://www.xanthus.com/news_2_13_06.htm