Merck KGaA to take on Biogen, Novartis with long-sought EMA nod for MS pill

Six years after regulators in both the U.S. and Europe said they wouldn’t approve Merck KGaA’s oral multiple sclerosis drug, cladribine, the German company has scored an unlikely victory, winning approval from the EMA to market it in 28 countries. The company will launch the pill first in the U.K. and Germany—and its executives are already talking about taking another pass at winning approval from the FDA.

Cladribine (now called Mavenclad in Europe) looked to be all but dead in 2011, when data from Merck’s only late-stage study suggested a possible link to cancer. The FDA and European Medicines Agency both concluded that the benefits of the drug did not outweigh its risks. The German company laid off thousands of people and closed its Swiss office, only to reveal four years later that, in fact, it planned to try again to get the drug approved.

The EMA’s thumbs-up was based on data from a phase 3 trial showing that cladribine cut annualized relapse rates by 67% and the risk of progression by 82% over placebo. The only significant side effects were herpes and a low white blood count, according to Merck. The drug is designed to be taken in two short courses over two years, and the company said the positive effects were sustained in years three and four without further treatment.

After Merck got a positive opinion on the drug earlier this summer from the EU Committee for Medicinal Products for Human Use, its executives hinted at a possible second pass at FDA approval. The company confirmed in a press release announcing the EMA approval that it is planning an FDA filing.

Merck will be counting on cladribine’s unique dosing schedule to help it stand out against the competition, which exploded during the time it spent completing its pivotal trials. Biogen’s Tecfidera, approved in 2014, is the market leader with nearly $4 billion in annual sales worldwide. Novartis’ Gilenya is not far behind, with $3 billion in sales, nor is Sanofi’s $1.5-billion-a-year Aubagio.

But those are all meant to be taken daily. Cladribine, by contrast, is given daily for just 5 days, twice in the space of two months. Then patients take the drug one year later, again for 10 days over the course of two months. The dosing schedule "is a pivotal change in the treatment of MS," said Belén Garijo, CEO of Merck KGaA’s healthcare division in the release.

Perhaps, but the German company’s marketing challenge will only intensify over time. Roche’s Ocrevus, approved in March, has a 6-month dosing schedule and impressive efficacy that has some analysts predicting it will shave 30% to 40% off sales of Tecfidera and Gilenya, even though it has to be infused.

Celgene’s phase 3 MS candidate, ozanimod, has also turned in impressive reductions in annualized relapse rates, not to mention a safety profile that could give the company a leg up in the market. Celgene plans to file for FDA approval by the end of the year.

Safety questions have cast a cloud over the MS market, however. The death of one patient in the Tecfidera trials led to an FDA warning and lost sales for Biogen. The company got the drug back on track with a controversial but effective direct-to-consumer ad campaign. Gilenya and Biogen's Tysabri have both been tied to a rare brain infection called PML. Given the initial questions about cladribine's safety, no doubt FDA reviewers will give the drug a thorough going-over before recommending it for approval.

Merck has not disclosed sales estimates for its new MS drug. But analysts in Europe have suggested it could bring in between €200 million ($236 million) and €400 million ($472 million) a year.