Dive Brief:

• Pierre Fabre Pharmaceuticals has asked the Food and Drug Administration for an urgent meeting to discuss why the agency rejected a cell therapy for a post-organ transplant malignancy, the company said Tuesday, following claims by partner Atara Biotherapeutics that the agency contradicted its previous guidance.
• The rejection issued in January was the second for the therapy, called Ebvallo, which had first been turned back due to manufacturing issues Atara later addressed. Atara said that in spurning Ebvallo again, the FDA reversed an earlier position and claimed that the evidence supporting the company’s application was no longer sufficient.
• The regulatory dispute over Ebvallo is one of a series of recent squabbles between drugmakers and the FDA related to previous agreements on approval standards. On Monday, UniQure learned it will have to conduct another trial of a Huntington’s disease gene therapy. Last month, the agency initially refused to review a flu vaccine from Moderna before quickly changing course.

Dive Insight:

Ebvallo treats a deadly complication of organ and stem cell transplantation linked to Epstein-Barr virus infections. Called post-transplant lymphoproliferative disease, the condition involves the growth and spread of B cells and often presents as lymphoma that quickly becomes lethal.

Rituxan can help treat post-transplant lymphoproliferative disease, but not everyone responds. Ebvallo is designed for those that don’t, and was granted an approval in Europe in late 2022.  

Ebvallo’s path to market in the U.S. has proven trickier, however. Following the therapy’s second rejection, Pierre Fabre — which owns global commercial rights — requested a “Type A” meeting. These are the most urgent meetings between drugmakers and regulators, and are intended to resolve disputes, discuss clinical holds or trial plans. They must take place within 30 days of the FDA’s receipt of a request and can spur action fast. In Moderna’s case, for instance, a Type A meeting and reversal occurred within the span of a week. 

“We approach this meeting with a sense of urgency and strong support from the patient and medical communities as the lifespan of individuals with [the disease] is often measured in weeks to months following failure of standard treatment," said Adriana Herrera, CEO of the U.S. subsidiary of France-based Pierre Fabre, in a statement.

In revealing Ebvallo’s rejection in January, Atara said it had previously aligned with FDA leaders on the design of Ebvallo’s key study over “multiple documented meetings” over the last five years. The drug had also received a “Breakthrough Therapy” designation and “Orphan Drug” status, highlighting the agency’s interest in getting it to patients, Atara said.

The situation is emblematic of the kind of surprise shifts in regulatory decision-making that have occurred under FDA Commissioner Marty Makary and top deputy Vinay Prasad, Cantor Fitzgerald analyst Eric Schmidt wrote in a January note to clients.

After speaking with Atara CEO Cokey Nguyen, Schmidt wrote that the decision suggested a “seemingly stochastic resetting of regulatory goalposts based upon unilateral decisions by top FDA leadership.”