No storm for Sarepta, but has the FDA created its own tempest?

There are several striking things about Sarepta’s ($SRPT) FDA approval this week for its controversial and long-delayed DMD drug, but just how it gained approval from the U.S. regulator has become one of the most interesting, and perhaps just as controversial.

Let’s go back to the start of the year when a massive snowstorm stopped the FDA from sitting down to discuss the drug, extending its PDUFA date by three months.

Then in April, more bad news when the agency’s group of experts rejected the med.

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A month later, things took another turn when the FDA said it would miss its own preset PDUFA date of 26 May in order to sort out “internal conversations” about the drug. Many started to believe a rejection was coming.

Then, just a few weeks later, the FDA went a knockin’ at Sarepta for fresh data on the key biomarker for efficacy, and some optimism grew again.

Things then took a strange turn earlier this month when Dr. Ron Farkas, a fierce critic of Sarepta’s DMD drug, left the FDA unexpectedly to take on a consulting role at CRO Parexel ($PRXL), with no word from any party until reports of the move surfaced in the press, and each were forced to concede that he had moved on. Reasons for his departure were not given.

Some believed this was a sign of dissent from within the agency and that Dr. Farkas’ leaving was a signal that an approval was coming. A week after his move went public, eteplirsen, now known as Exondys, gained what seemed at times one of the most unlikely of approvals.

It was unlikely because much of the data used to back a speedy approval were based largely on a small study with no placebo control, comparing eteplirsen's results against historical data in the muscle-wasting disease.

Back in April, the FDA panel of outside experts voted narrowly, 7 to 6, that Sarepta did not provide substantial evidence from “adequate and well-controlled” studies that the drug produced dystrophin at a level that was reasonably likely to produce a clinical benefit.

On the big question--Do the clinical results of the single study provide “substantial evidence” of eteplirsen’s efficacy--7 of the panel members voted no, with three voting yes and three abstaining.

Five months down the line, however, it has been approved, and Sarepta’s shares soared into the afternoon, up by more than 90% after midday.

One of the big pressures for the FDA has been the lobbying power from hundreds of patient advocates, patients and families that have turned out to give their raucous support for an approval during the panel review and vote.

And backers have continued to protest--with widespread support from prominent elected officials and newspapers--that this is their last and only near-term hope for a drug that they insist has made a dramatic difference for slowly dying boys with this terrible disease that until this week had no specific treatments.

We may never know how much this lobbying helped in the approval of the drug, but one thing that has now come to light is the internal lobbying undertaken by Dr. Janet Woodcock, the CDER director.

In redacted documents released along with the approval, it is clear that it was Dr. Woodcock who helped push the drug through to approval--despite internal protestations from Dr. Ellis Unger, a senior doc at the agency, to FDA Commissioner Dr. Robert Califf.

Dr. Unger, among others, had expressed concerns at the small study and its lack of clear efficacy, but Dr. Woodcock, who in the past has been seen by some as leaning toward approvals rather than rejections, said the FDA must be “Prepared to be flexible with respect to a devastating illness with no treatment options.”

Last week, Dr. Califf said he would “defer” to Dr. Woodcock in this case and allow the green light.

In a more astonishing moment, detailed in the CDER documents, Dr. Woodcock said that Sarepta in particular “needed to be capitalized” and noted that the biotech’s stock had risen and fallen on a series of updates over the year.

In the documents, it recorded: “Dr. Woodcock cautioned that, if Sarepta did not receive accelerated approval for eteplirsen, it would have insufficient funding to continue to study eteplirsen and the other similar drugs in its pipeline. She stated that, without an approval in cases such as eteplirsen, patients would abandon all hope of approval for these types of products and would "lapse into a position of" self-treatment.

This will likely lead to some serious questions over the FDA’s processes and whether this sets a precedent for other rare and ultrarare meds--and how much a company’s stock and concerns over future research should be considered. Many at the agency clearly felt the question was over the data, so where does this leave the broader questions in future decisions?

Sarepta will under the approval still need to show more data that its drug works, or face having it yanked off the market. Some will see this as a flexible approach in a disease with no treatments, but others may question why a drug should gain approval, and then earn potentially hundreds of millions of dollars, if it turns out it did never did meet the regulator’s efficacy requirements.