Biogen's Fampyra Gains Conditional Approval In Europe

Biogen must prove additional drug benefits in further study to gain full approval.

Biogen Idec Inc.'s Fampyra (fampridine) received conditional marketing approval from the European Commission to improve walking in adults with multiple sclerosis, the company announced July 25.

The outcome was expected given the positive recommendation in May 2011 by the European Medicines Agency's Committee for Medicinal Products for Human Use (CHMP) (Also see "Amid A Flurry Of EU Positive Opinions Benlysta And Yervoy Shine, While Fampyra Is Reborn" - Pink Sheet, 20 May, 2011.). That recommendation followed a surprise negative opinion on Fampyra from the CHMP in January 2011, which Biogen successfully appealed.

Fampyra, the only approved treatment for walking disability in MS, will become Biogen's third marketed drug in Europe aimed at the MS community. The company already sells Avonex (interferon beta-1a) and Tysabri (natalizumab) to treat the underlying disease.

To obtain unconditional approval for Fampyra in Europe, Biogen must conduct another study to uncover further benefits of the drug beyond its effect on walking speed, the only measured outcome in trials to date. Biogen claimed it already was planning such a study, although it doesn't yet know what measurable endpoints it will use. "It's difficult to find an endpoint for a symptom in a clinical trial," observed a spokesperson for the company.

Indeed, in its original rejection of the drug, the CHMP had questioned whether its beneficial effect on walking speed was meaningful, all the more so given Fampyra's side-effects, which include seizures and insomnia. Companies aren't allowed to submit new data during the appeal process, but Biogen said it re-packaged the existing data to better demonstrate the drug's impact on walking, and the CHMP re-examination looked into what specific group of patients was most likely to benefit from the drug, a potassium channel blocker.

Biogen was all the more confident in its appeal given that the same product was approved by FDA in the U.S. in January 2010 as Ampyra, despite similar questions about the clinical meaningfulness of the drug's benefits (Also see "FDA Approves Ampyra Despite Slight Responder Rate and Seizure Risk" - Pink Sheet, 22 Jan, 2010.).

Acorda Therapeutics Inc. developed Ampyra and markets it in the U.S; Biogen licensed ex-U.S. rights in July 2009. Under the arrangement, Biogen will pay Acorda royalties on ex-U.S. sales, as well as a $25 million milestone payment for the European approval. Elan Corp. PLC, whose technology was used to develop the drug, is eligible for 7% of this and all further milestones paid by Biogen to Acorda, which could reach $375 million.

Conditional Approvals Still Rare

Biogen's confidence notwithstanding, the conditional approval "wasn't an obvious outcome," said a company spokesperson, given that so few such approvals have been granted in Europe.

Despite the EMA's stated support for such approvals, designed to accelerate access to new drugs that treat unmet needs even when additional data are required, only nine have been granted since the process was first adopted in 2008.

Fampyra's is the second conditional approval in 2011, alongside that of Novartis AG's Votubia (everolimus) for use in certain brain tumors (Also see "CHMP Positive On Trajenta, Vectibix, Votubia And Eurartesim, But Negative On Bronchitol, Luveniq And Glybera" - Pink Sheet, 27 Jun, 2011.).

GlaxoSmithKline PLC's Votrient (pazopanib) for renal cell carcinoma was one of four such approvals in 2010 (Also see "GSK's Votrient Gains Conditional EU Approval For Renal Cell Carcinoma" - Pink Sheet, 15 Jun, 2010.).

EMA's conditional approvals process is equivalent to the FDA's accelerated approval pathway - with a few differences ('FDA and EMEA: Minding the Gap,' The IN VIVO Blog, May 21, 2009).

One is that European regulators review conditional approvals annually. Biogen said it has been given longer than a year to undertake its additional study, though, which means Fampyra's first annual review will likely focus on any safety data generated during the 12 months (Biogen also is conducting a post-marketing safety study, as for any new product). The CHMP may at that point re-issue a conditional approval, or grant full approval, or recommend the drug's authorization be withdrawn, although the last scenario has never yet arisen, according to an EMA spokesperson.

Another difference is that EMA can impose financial penalties on any company which fails, within an agreed timeframe, to comply with the conditions of a conditional marketing authorization. FDA under certain conditions can impose non-compliance fines related to safety studies under FDAAA, but most post-market trials in the accelerated approval context are efficacy related.

Fampyra "Rounds Out" Biogen's MS Portfolio

Biogen expects to launch Fampyra first in September in Germany, Europe's largest market. The company wouldn't comment on its reimbursement strategy, but expects the price of the drug to be "about half" of that in the U.S., where the list price is about $14,000 per year - although price will vary by market.

Biogen's Avonex and Tysabri, co-marketed with Elan Corp. PLC, together generated $3.7 billion in sales in 2010, or almost 80% of the group's total revenues. No one is expecting Fampyra to match either of these, given its niche indication: Lazard Capital Markets' Joel Sendek estimates ex-U.S. sales of $221 million by 2014, with a $34 million royalty due to Acorda that year. But Fampyra, an orally available drug which can be taken with any other marketed disease-modifying therapy for MS, rounds out Biogen's portfolio.

Avonex and Tysabri both turned in strong second quarter sales results, which Biogen announced July 26, despite new competition in the market from the first oral disease-modifying agent for the disease, Novartis' Gilenya (fingolimod), approved in the U.S. in October 2010. Sales of Avonex were up 4.9% to $659.3 million and sales of Tysabri increased 28.3% to $281.4 million. Biogen also is developing an oral drug for MS, BG-12, with data from a second Phase III trial expected in the second half of the year.

- Melanie Senior ([email protected])