Exon Skipping

Exon-skipping drugs remove the mutation, creating a functional protein. Source: Sarepta Therapeutics.

The race is on between Sarepta Therapeutics (NASDAQ:SRPT) and BioMarin Pharmaceuticals (NASDAQ:BMRN) to bring the first Duchenne muscular dystrophy drug for patients who can be helped with an exon 51-skipping drug.

Both drugs are getting priority reviews from the agency, highlighting the unmet need in Duchenne muscular dystrophy. BioMarin Pharmaceuticals' drisapersen has a two-month head start with a Food and Drug Administration target action date of December 27. Sarepta's date with destiny for eteplirsen is February 26.

Normally, accepting the applications and assigning an action date wouldn't be that big of a deal, but both drugs have blemishes that make their applications less than perfect.

Sarepta Therapeutics has had an on-again, off-again relationship with the FDA. The biotech was stunned in 2013 when the FDA said it didn't think the limited phase 2 data Sarepta had was enough to approve the drug. But since then, Sarepta has said the FDA has reversed course and encouraged the company to apply for approval.

BioMarin's drisapersen failed a phase 3 trial, but Prosensa, the owner of the drug before BioMarin bought the company, talked with the FDA, which agreed to a regulatory path forward as long as Prosensa agreed to run two post-approval clinical trials.

Black box (but not for long)
Investors' anxiety about the FDA accepting the applications has to do with the lack of transparency for the interactions between the companies and the FDA. Investors only get one side of the story from the companies. Management will say the FDA offered "positive feedback" about submitting an application or that the FDA "agreed" with the company's plans, but there's no way for investors to verify it because the agency doesn't talk publicly about unapproved drugs.

For drisapersen, at least investors were able to get a second opinion from BioMarin, which subsequently purchased Prosensa. The biotech presumably saw the meeting minutes and was clearly confident that the agency would accept the application.

Investors won't have to wait too much longer to get a first-hand look at what the FDA thinks of the drugs when they are reviewed at an advisory committee meeting. A meeting for the Peripheral and Central Nervous System Drugs Advisory Committee has been tentatively scheduled for November 23 and 24. One day would presumably be used to review drisapersen and the other for eteplirsen although the FDA hasn't formally said that since the meeting is still tentative.

Two business days before the advisory committee meeting, the FDA's summary of its review of the drugs and questions for the committee will be available on its website. Assuming the meetings are on separate days, investors in the company that goes second will have to wait an extra day.

Likelihood of an approval?
Considering how much feedback both companies have gotten from the agency before even submitting their applications, it seems the FDA wants to approve the drugs.

The advisory committee meetings are a bit of a wild card. If the committee of outside experts recommended that the drugs not get approved, it's hard to see the FDA going against their recommendation. Luckily for the companies, advisory committees tend to be willing to overlook less-than-perfect data for diseases that don't have any approved drugs. Many doctors, who make up most of the panel, figure something that may work is better than nothing at all.

It's always possible that the FDA will approve one drug but not the other, but it's hard to say which data package is worse.

BioMarin Pharmaceuticals failed its only phase 3 trial. But the company will argue that drisapersen worked well in the two phase 2 trials and the reason the drug failed in phase 3 was because the trial enrolled older patients that had advanced to a point where the drug wasn't as helpful.

The data for eteplirsen comes from a small phase 2 trial, so the drug hasn't been tested on nearly as many patients as drisapersen. The upside is that the data is much cleaner in large part because the patients have been on the drug for so long. Since this is a progressive disease, the lack of deterioration is a good sign that the drug is working even if there isn't any true placebo control at this point since those patients were switched over to the drug a while ago. Data from a fourth biopsy to see if there's still expression of dystrophin -- the protein missing in Duchenne muscular dystrophy patients that eteplirsen restores -- is expected in October and can be added to the application, presumably before an advisory committee meeting.

The tiebreaker could come down to the post-approval trials to confirm that the drugs work. If the FDA is worried that it's approving something that doesn't work, the faster the companies can confirm or disprove that worry, the less of a concern it'll be.

Sarepta has BioMarin beaten in this category because its confirmatory trial, PROMOVI, has already started and should be fully enrolled by the end of the year. BioMarin doesn't plan on starting its confirmatory trials until after the details are worked out during the review process.

Brian Orelli has no position in any stocks mentioned. The Motley Fool recommends BioMarin Pharmaceutical. Try any of our Foolish newsletter services free for 30 days. We Fools may not all hold the same opinions, but we all believe that considering a diverse range of insights makes us better investors. The Motley Fool has a disclosure policy.