FDA, Regulatory

Amicus CEO lobbied FDA to reverse FDA’s rejection of migalastat, claiming a delay of up to 7 years

Handwritten Note from John Crowley to Scott Gottlieb.


Five days after Scott Gottlieb was sworn in as head of the FDA last May, Amicus $FOLD CEO John Crowley was personally lobbying him to reverse a stinging rejection of migalastat, his new drug for rare cases of Fabry disease.

CEO John Crowley

He overnighted a letter — obtained by the Project on Government Oversight — to Gottlieb explaining that the company had determined that it would take an extraordinary 5 to 7 years to complete a Phase III study of gastrointestinal symptoms that the agency had determined would be required before it could consider offering a green light for marketing. That would not be feasible in a reasonable amount of time, he said. And he reviewed new data that had been shared with CDER director Janet Woodcock, the FDA’s Julie Beitz and others at her request.

The letter came with a handwritten note from Crowley evidently following a personal conversation with Gottlieb, a high profile figure in the biotech world.

“Congratulations, again!” he wrote. “As discussed, the hopes and well being of so many living with rare, devastating diseases rests now with your great leadership and wisdom. Thanks for your attention to the attached.”

In his formal letter, Crowley repeated two questions that had been pitched to Woodcock. Did the agency agree a new Phase III would not be needed? Would the agency review a new NDA?

Summed up Crowley: “We are committed to move most expeditiously to submit the NDA once we have clarity on the above.”

Scott Gottlieb

The answer to his questions from the agency was a stunning yes, one of three key reversals that the FDA made in the weeks and months after Gottlieb took the helm of the FDA. Like Amicus, Eli Lilly successfully appealed the unexpected rejection of baricitinib, which is now back under review. Then a few weeks ago TherapeuticsMD — rejected a day ahead of Gottlieb’s confirmation — was also handed a stay of execution.

As the FDA reversed itself on migalastat July 11, sending its share price soaring, Leerink’s Joseph Schwartz noted:

We also cannot rule out the political influence of a new administration (and its inclination toward approving medicines for deadly afflictions) having an influence in today’s announcement.

The sudden changes in stance at the agency raise serious questions. In executing these three reversals after Gottlieb was sworn in, has the agency lowered the bar on its data demands for new meds? And what role did Woodcock — the controversial champion of eteplirsen who stared down fierce internal opposition to approve Sarepta’s drug on sparse data — as well as Gottlieb play in pushing for the agency’s changing stance on these drugs?

I’ve asked the FDA for clarification on this before, but never got any formal response at the time. The agency, though, is also bound by strict rules restricting what it can say about any one company. Gottlieb, however, is not restricted from discussing the agency’s changing approach to drug reviews in general, as he has demonstrated many times in recent months.

Friday afternoon, acting assistant commissioner Jennifer Rodriguez contacted me to say that Gottlieb was unaware of the letter. Her comment:

Dr. Gottlieb was not involved in this matter and further, he was not aware of this letter. Product-specific correspondence that is sent to Dr. Gottlieb by external parties is referred to the relevant centers as a matter of routine procedure. Further, decisions on whether to accept to file an application or grant a drug application priority review (or any of the other pathways for drug review) is based on specific criteria applied to the product’s data and determined by appropriate FDA career staff. To confirm, Dr. Gottlieb was not involved in decisions related to this product review.

I followed up to ask if Woodcock, a powerful FDA official who Crowley says he had met with, felt Crowley’s pitch about an infeasible delay of 5 to 7 years was considered a credible reason for a reversal, and if so, why. All my original questions stand unanswered.

Rodriguez’s followup:

Dr. Gottlieb was not involved in this matter and was not involved in discussions about this product-specific decision.

With respect to your other questions, the FDA generally cannot discuss the status of a pending application. The FDA is able to provide information on approved drug product applications. Information on an application that has yet to receive an approval or was denied approval generally is not releasable.

I didn’t hear back on whether Gottlieb knew what Crowley may have referred to in saying “as discussed” in his warm personal note.

In making a point, Crowley’s assertion that it would take up to 7 years to complete the required Phase III also begs questioning. That process was widely expected to take about 3 years, fairly standard for this kind of a move.

In the company’s detailed response to the rejection, Amicus said it would have the data in 2019.

Amicus is working with FDA to finalize the clinical protocol and plans to initiate enrollment in 2017, with data expected in 2019

Did Crowley push that number up to see if it would help persuade regulators — particularly Gottlieb or Woodcock — to change their minds? And wouldn’t he have to tell investors, if that was the case?

We pitched those questions to Crowley through his media contact, and he didn’t provide a direct response. Instead, we got this:

Our engagement with the FDA, as with other regulatory bodies around the world, has been focused on the science and data we have advanced through a decade of clinical research in Fabry disease, as well as our understanding of the significant patient needs we have learned from the Fabry community. Our NDA submission includes a robust data package including the two largest Fabry pivotal studies ever conducted – which supported approvals in the EU, Switzerland, Israel, Canada and Australia.

Over a series of discussions with the FDA throughout the first half of this year, we had the opportunity to share: 1) new data; 2) new analyses of existing data; 3) longer-term data from our extension studies; 4) the experience of patients on commercial Galafold in Europe (especially those transitioning from ERTs); and, 5) as requested by FDA, patient perspectives on the unmet need in Fabry disease and the lack of treatment options in the U.S.  All of this culminated in the confirmation from FDA that we could submit the NDA, which we did on December 13.

As CEO of Amicus, I am dedicated to advocating in the best interest of patients.  We stand firmly behind our engagement with FDA, and remain committed to advancing migalastat through the regulatory process as quickly as possible.

In the meantime, Amicus pushed through its new NDA for migalastat yesterday.


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