The Biotech Scramble for Big Money in Muscular Dystrophy Drugs

Failed test results do not deter determined startups seeking FDA approval.

Politicians and media observers are focusing on the spectacular prices some biotech companies seek to charge for drugs for rare diseases. The hunt for a treatment for the deadliest strain of muscular dystrophy is likely to return the issue to the spotlight and raise questions about how regulators evaluate cutting-edge drugs.

Three companies are competing for Food and Drug Administration approval of medicines for Duchenne, a disease that destroys muscle, robs victims of the ability to walk, causes respiratory complications, and typically leads to death by the mid-20s. One in 3,500 newborns has Duchenne, almost all of them boys. There's no cure. An FDA-approved Duchenne treatment would likely carry a price tag of $300,000 a year or more, making the drug a billion-dollar bonanza for its manufacturer.

But before getting to the question of revenue and profit, there's the issue of whether ultra-expensive drugs do much good. Some clearly do. Gilead's new medicines for hepatitis C can cost up to $94,500 for a 12-week course of treatment, and they've proven to be an effective cure for the devastating disease. If the Gilead drugs preclude lengthy hospital stays, they're arguably well worth the cost.

In contrast, ambiguity clouds the prospects of some of the Duchenne treatments, which may add years to patients' lives but are not complete cures. On Oct. 15, PTC Therapeutics announced its drug failed to help boys with the muscle-wasting ailment walk better in a final-stage clinical trial. In a trial of 228 patients, PTC said boys on its experimental drug walked 15 meters farther in a six-minute test than subjects on a placebo. That difference isn't considered statistically significant, PTC acknowledged.

Nevertheless, the company held out hope for FDA approval. PTC said that when it blended results from the failed Phase III trial with those of a previous study and performed a "meta analysis," it could discern a statistically significant improvement of 22 meters on the walking test. "We're excited because the totality of the clinical data [does] confirm the benefit we previously saw in the Phase II study and, in our perspective, supports the benefit of Translarna," the PTC drug, Shane Kovacs, the company's chief financial officer, told Bloomberg News.

In 2014, I interviewed PTC's co-founder and chief executive, Stuart Peltz, about an earlier failed trial that had seemed to doom Translarna (the trade name for ataluren). "We shot ourselves in the foot" by conceding defeat after the failed 2010 trial, Peltz told me. He maintained that reanalysis of the failure transformed it into a success: "In biotech, you're building the airplane while you're trying to fly it at the same time." In August 2014, EU regulators tentatively allowed PTC to begin selling Translarna in Europe. 

Christopher Marai, an analyst at Oppenheimer, said the company's results, however dubious, will probably help win FDA approval. "We believe these results will be enough to keep Translarna on the market in the EU and garner FDA approval in the U.S.," Marai wrote in a note to clients.

BioMarin's Duchenne drug candidate, drisapersen, targets a different genetic flaw. Drisapersen goes before an FDA advisory committee in late November. The FDA agreed to evaluate BioMarin's medicine even though it failed its main clinical trial in 2013 and has caused potentially troubling side effects in some patients. Drisapersen's developers have blamed faulty testing methods and predicted that the drug ultimately will prove effective and safe.

The third Duchenne treatment, eteplirsen, manufactured by Sarepta Therapeutics, has shown the most promising test results for effectiveness and safety. But the main trial of eteplirsen involved only 12 boys, prompting some skeptics to question its reliability. A passionate cadre of parents of Duchenne boys who've tried eteplirsen want the FDA to approve it while Sarepta continues research. An FDA advisory committee is scheduled to review eteplirsen in January. 

Chris Garabedian, a former Sarepta CEO who pushed hard for FDA approval for eteplirsen, says the drug deserves to be tried more widely. “As the FDA considers approval of various drugs for Duchenne muscular dystrophy," he says, "it seems there should be more emphasis on the quality and consistency of the clinical and biochemical outcomes, as well as safety, rather than the sheer number of patients that have been evaluated, especially for such a rare and terminal disease as Duchenne.”

Patients, their families, and Wall Street investors are all watching how the FDA follows through on the Duchenne story. Lives and many dollars weigh in the balance.


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