Replimune (REPL)

[jondoeuk]

From this (behind a wall): ''Replimune is waiting for the FDA to further explain last week’s surprise rejection of its advanced melanoma treatment before engaging in the formal process that pharma companies typically take to resolve the agency’s questions and concerns in a complete response letter.

Replimune’s founder and executive chairman Philip Astley-Sparke told Endpoints News in an interview Friday that the company has asked the FDA to provide more details on what exactly it wants from the therapy to move forward, but has yet to have any dialogue.

“There’s a lot of speculation, but we do not know for certain. And before we interact with the agency in any more formal way, we would actually like to understand from the agency what led to such a drastic pivot,” Astley-Sparke said.

Replimune’s treatment, called RP1, is an HSV-1-based oncolytic immunotherapy that was tested in combination with Bristol Myers Squibb’s PD-1 inhibitor Opdivo for advanced melanoma.

An accelerated approval seemed to be all but certain leading up to the July 22 decision date. The FDA hadn’t requested an advisory committee and the biotech said it was in label negotiations with the agency, and had already completed manufacturing inspections and clinical trial site inspections — the usual final steps ahead of an approval.

When it received a CRL from the FDA instead, Replimune said that the issues that were raised hadn’t been part of its dialogue with the agency leading up to the action. According to the company, the FDA said the CRL was the result of the “heterogeneity” of the patient population in the pivotal trial, and the potential that Opdivo might be driving patients’ responses.

But the idea that size of the effect could be from Opdivo alone “just doesn’t hold water,” Astley-Sparke argued

Replimune added that the FDA also took issue with the design of a confirmatory trial that was necessary to get an accelerated approval, even after aligning on the design of that trial with the agency. Astley-Sparke said it’s unlikely the company will be able to complete the study if the market doesn’t think there’s a shot at approval.

“That study is very much still enrolling, but we would not be able to finance it,” he said.

Astley-Sparke declined to comment further on the confirmatory study since the company isn’t exactly clear on what the agency wants, he said.

After losing almost 80% of its value after the CRL, Replimune’s stock has rebounded in recent days; investors have been encouraged that Vinay Prasad’s exit from CBER might change its fortunes.

Astley-Sparke confirmed the rise is likely the result of investors thinking RP1 will ultimately win an accelerated approval.

There has also been speculation of whether FDA leaders, including Prasad, might have driven the Replimune rejection, overruling scientific staff.

A now-deleted comment from a CBER branch chief on LinkedIn said agency “leadership” did not agree with the clinical review team’s assessment of RP1, and then pushed the CRL. A former senior leader in CBER told Endpoints last week that the Replimune CRL came from Rick Pazdur, director of the FDA’s Oncology Center of Excellence.

Astley-Sparke said he had heard “rumors” of Pazdur’s involvement, but he noted that Pazdur “does not have signature authority over CBER decisions.” The FDA didn’t respond to a request for comment on Friday, and Pazdur didn’t respond to a question sent directly to him.'' https://endpoints.news/replimune-says-its-waiting-for-fda-on-a-path-forward-for-rejected-cancer-treatment/