Sarepta Therapeutics won one of the most controversial drug approvals in recent memory, when the FDA in September 2016 approved the Duchenne muscular dystrophy drug eteplirsen (Exondys 51) off a slim set of data. The Cambridge, MA, company isn’t having the same luck in Europe.
Sarepta (NASDAQ: SRPT) said today that the Committee for Medicinal Products for Human Use, which helps guide drug approval decisions in Europe, has rejected eteplirsen for the second time. The CHMP first declined to recommend eteplirsen for approval in May. Sarepta called for a re-examination of its approval application, but got the same result. It expects European regulators to formally reject the drug by the end of the year.
As it has in the U.S., Sarepta sought approval of eteplirsen, a drug for a 13 percent genetic subset of Duchenne patients, before obtaining definitive proof in clinical trials that the drug actually benefits patients. That strategy worked with the FDA. In a decision that caused an internal rift at the agency—and many, at the time, worried would set a precedent for future drug approval decisions—Sarepta was cleared to sell eteplirsen in the U.S. because it was “reasonably likely to predict clinical benefit,” largely off of data from a 12-patient study showing it may help produce dystrophin, a muscle protecting protein that Duchenne patients lack. It was the first-ever drug in the U.S. specifically approved for Duchenne, a progressive and fatal inherited disease.
Sarepta was told to initiate a post-approval study to confirm its benefits, but in the meantime, after some early battles with insurers, eteplirsen has done well commercially. It generated $154.6 million in sales in 2017 and is expected to double that total this year. What’s more, the approval decision has been a springboard for Sarepta to raise cash and invest in more Duchenne treatments. It expects to file for approval of golodirsen, a follow-on Duchenne drug for a different genetic subset of patients, next year. A Duchenne gene therapy that Sarepta licensed from Nationwide Children’s Hospital has shown early promise in its first human test. Shares are trading near all-time highs.
Still, Sarepta has run into a wall so far in Europe. In May, the CHMP said Sarepta’s methods for comparing eteplirsen’s results to a “historical control”—previous data on patients deemed to have similar characteristics to those who took the drug—weren’t good enough to prove the drug is effective. “The committee considered further data were needed to show that the very low amounts of shortened dystrophin produced as a result of [eteplirsen] treatment bring lasting benefits relevant to the patient,” the CHMP wrote in its decision. It confirmed that decision again today.
Sarepta CEO Doug Ingram said in a statement that the company plans to explore a path forward in Europe “that balances the needs of patients and their families to avoid lengthy and unnecessarily burdensome trials with those of European regulators for additional supportive data consistent with existing European regulations.” It will seek more advice from regulators there next year.