According to reporting from multiple outlets, Richard Pazdur, head of the Oncology Center of Excellence at CDER, opposed the consensus opinion of CBER staff to approve the drug. Replimmune’s stock has dropped precipitously since the rejection.
Two weeks ago, Replimmune received a surprise rejection from the FDA for its advanced melanoma drug, RP1. New reporting from multiple outlets reveals that the agency’s top cancer regulator directly intervened to issue the complete response letter.
Richard Pazdur, director of the FDA’s Oncology Center of Excellence (OCE) and acting director of the Office of Oncologic Diseases, both offices within the Center for Drug Evaluation and Research (CDER), had a hand in issuing the complete response letter to Replimmune, according to reporting Friday from Endpoints News, with confirmation from STAT News on Monday.
“This was Rick Pazdur’s doing,” an FDA official told STAT on the condition of anonymity. “I didn’t agree with all the decisions made here by Vinay [Prasad], but he had little to do with this one.”
Replimmune’s stock crashed 75% after the rejection and was down another 30% Monday morning after market open.
The rejection appears to have come down to a late intervention from CDER into a review at its sister office, the Center for Biologics Evaluation and Research (CBER), where RP1 was under review. Another anonymous FDA official said that CBER had “mishandled” the review, prompting Pazdur and OCE to get involved.
RP1 is a herpes virus–based immunotherapy that induces an immune response against tumors. It was being tested in combination with BMS’ immunotherapy Opdivo.
When the rejection came down, speculation swirled that the CRL was related to the design of the trials that provided supporting data. Pazdur and his team, according to STAT, were indeed troubled by the design, saying that the drug’s tumor killing effect could not be separated from the effect elicited by Opdivo.
“The issues highlighted in the CRL were not raised by the agency during the mid- and late-cycle reviews,” Replimmune CEO Sushil Patel said in a statement on July 22nd announcing the news. “Additionally, we had also aligned on the design of the confirmatory study.”
Then-CBER director Vinay Prasad attended a conference in early July, along with Pazdur, where the merits of RP1 were debated. The consensus from the CBER side was that RP1 should be approved, but Pazdur was in opposition. Prasad ultimately deferred to Pazdur, according to STAT.
A week after the Replimmune CRL, following a hail of criticism from conservative figures centered on a variety of issues, including his handling of Sarepta’s gene therapy Elevidys and his past support for progressive policy positions, Prasad left the agency.
Replimmune intends to request a follow-up meeting with the FDA to understand how to move forward.
