http://www.medscape.com/viewarticle/540389

Yael Waknine

July 10, 2006 — The European Commission has approved a recombinant parathyroid hormone once-daily subcutaneous injection for the treatment of postmenopausal osteoporosis in women at high risk for fractures and natalizumab monotherapy to delay the progression of disability and reduce the frequency of relapses in patients with relapsing remitting multiple sclerosis; Australia's Therapeutic Goods Administration has approved a new indication for zanamivir, allowing its use for the prophylaxis of influenza in patients aged 5 years and older.


Recombinant Parathyroid Hormone Injection (Preotact) for Postmenopausal Osteoporosis in EU

The European Commission approved in April recombinant [rDNA origin] parathyroid hormone [PTH] subcutaneous injection (Preotact, made by NPS Pharmaceuticals and marketed by Nycomed) for the treatment of postmenopausal osteoporosis in women at high risk for fractures. The marketing authorization is valid in all 25 member states of the European Union.

In contrast with teriparatide (Forteo, made by Eli Lilly and Company), the recombinant protein is full-length and contains all amino acid fragments.

The approval was based primarily on 18-month data from the multicenter, randomized, double-blind, placebo-controlled, phase 3 Treatment of Osteoporosis with PTH (TOP) trial (N = 2600), showing that once-daily use of the recombinant PTH product significantly reduced the risk for first and subsequent vertebral fractures by 66% and 69%, respectively, in postmenopausal women who had received at least 75% of the prescribed doses (per-protocol patients, n = 1870).

Results also showed that per-protocol patients receiving PTH experienced significant increases in mean spine, total hip, and femoral neck bone mineral density compared with placebo.

According to a company news release, PTH was linked to transient increases in serum calcium. During the TOP study, increases of more than 10.7 mg/dL in serum calcium levels from baseline were observed in 21% of patients treated with the study drug vs 3% of those receiving placebo; the associated discontinuation rate was 0.7%.

The PTH product (Preos, made by NPS Pharmaceuticals) is currently being considered for approval by the US Food and Drug Administration.


Natalizumab (Tysabri) for Relapsing Remitting Forms of MS in EU

On June 29, the European Commission approved natalizumab intravenous infusion (Tysabri, made by Biogen Idec and Elan Corporation, plc) for use in all 25 member states of the European Union as monotherapy to delay the progression of disability and reduce the frequency of relapses in patients with relapsing remitting multiple sclerosis (MS). The drug is intended for use in patients with high disease activity despite treatment with a beta-interferon and in those with rapidly evolving severe disease.

According to a company news release, the approval was based on a submission that included 2-year phase 3 clinical trial data; findings from a comprehensive safety evaluation; suggested labeling; and a risk management plan designed to inform physicians and patients of the benefits and risks of natalizumab therapy, thereby minimizing the potential risk for progressive multifocal leukoencephalopathy (PML) and other opportunistic infections.

The monoclonal antibody was first approved for this indication by the US Food and Drug Administration (FDA) in November 2004 and was later withdrawn from the market by the manufacturer in February 2005 after 3 patients developed PML during clinical trials.

Because 2 of the patients were also taking interferon beta-1 alpha (Avonex, made by Biogen Idec), a causal role for natalizumab was not established. On June 5, 2006, the FDA allowed the reintroduction of natalizumab into the US market with a restricted distribution program and revised safety labeling to warn of the risk for PML.


Zanamivir for Inhalation (Relenza) to Prevent Influenza in Adults and Children

On May 1, Australia's Therapeutic Goods Administration (TGA) approved a new indication for orally inhalable zanamivir (Relenza with Diskhaler, marketed by GlaxoSmithKline under license from Biota Holdings Ltd), allowing its use for the prophylaxis of influenza in patients aged 5 years and older.

The approval was based on a review of data from 4 large-scale, placebo-controlled studies. In 2 studies of postexposure prophylaxis in households with members aged older than 5 years, use of zanamivir within 1.5 days of symptom onset for treatment of the index case and its prophylactic use in other household members were equally effective for significantly reducing the spread of influenza (4.1% vs 19.0%).

Results from the other 2 trials showed that zanamivir significantly reduced the risk of developing influenza symptoms in adults aged 18 years and older (mean age, 29 years; 86% unvaccinated) and individuals aged 12 to 94 years (mean age, 60 years) during community influenza outbreaks (56% aged older than 65 years; 67% unvaccinated; 2.0% vs 6.1% and 0.2% vs 1.4%, respectively).

Zanamivir should be administered at approximately the same time each day. The recommended dose of zanamivir for household prophylaxis in patients aged 5 years and older is 10 mg (inhalation of two 5-mg blisters) once daily for 10 days, initiated within 1.5 days of symptom onset in the index case.

For the prophylaxis of influenza in a community setting, the recommended regimen for zanamivir in adults and adolescents is 10 mg daily for 28 days, initiated within 5 days of the outbreak being identified. The safety and efficacy of this regimen has not been studied beyond 28 days.

Because of the risk for potentially fatal bronchospasm, zanamivir should not be used in patients with underlying airway disease, such as chronic obstructive pulmonary disease or asthma.

Zanamivir should be discontinued in patients who develop bronchospasm or demonstrate a decline in respiratory tract function; immediate treatment and hospitalization may be required. Some patients without prior pulmonary disease may also have respiratory tract abnormalities from acute infection that could resemble an adverse reaction or increase patient vulnerability to such reactions.

The indication was approved by the US Food and Drug Administration on March 29, 2006. Zanamivir was previously approved by the TGA and FDA for the treatment of uncomplicated acute illness due to influenza A and B virus in patients aged 7 years and older who have been symptomatic for no more than 2 days.

Reviewed by Gary D. Vogin, MD