The second time is not the charm for Replimune’s melanoma candidate RP1. After spurning the immunotherapy last July, the FDA has now rejected the biotech’s resubmitted application.
At the time of that initial rejection, the FDA determined that the phase 1/2 Ignyte trial of the oncolytic virus RP1, in combination with Bristol Myers Squibb’s Opdivo, was not “adequate and well-controlled,” while also adding that the heterogeneity of the patient pool made interpreting the trial’s results difficult.
In a complete response letter dated April 10, the FDA stated that reviewers from the Office of Therapeutic Products and the Oncology Center of Excellence had “unanimously determined data presented are insufficient to conclude substantial evidence of effectiveness.”
The decision puts the future of RP1 in doubt. In a February filing with the Securities and Exchange Commission, Replimune warned that a second rejection could lead it to “determine that the development of RP1 is no longer viable.”
In a press release, Replimune said it disagrees with the FDA's decision to not approve RP1.
“It is deeply disappointing that the FDA has not exercised regulatory flexibility to meet patients’ needs given the data supporting strong efficacy and the favorable safety profile,” Replimune CEO Sushil Patel, Ph.D., said in the release.
“Approximately 8,500 Americans with advanced melanoma die every year. The country's foremost melanoma specialists stood behind the
“As we previously communicated, without timely accelerated approval, the development of RP1 will not be viable,” the CEO added. “We are devastated for our committed employees who have worked tirelessly for patients but at this point we have no choice but to eliminate jobs, including substantially scaling back our U.S.-based manufacturing operations.”
The biotech is laying off 63 employees as a result of the rejection, according to an official layoff notice to the state of Massachusetts on April 13.
RP1, more formally known as vusolimogene oderparepvec, is an engineered strain of the herpes simplex virus designed to weaponize the patient’s immune system against cancer cells.
Replimune’s share price unsurprisingly plunged in response to the rejection, dropping around 20% from $5.91 at close of trading Thursday to $4.76 by 11:05 a.m. ET Friday. The Massachusetts-based biotech had previously enjoyed a stock boost after resubmitting RP1’s application.
For its review, the FDA reanalyzed data from the Ignyte trial and also considered new data from an ongoing phase 3 trial that Replimune added to its resubmission.
Even with fresh eyes, the agency still determined that the Ignyte data “do not alter our initial conclusion” that the trial was not up to par. For the new trial data that Replimune hoped might tip the scales in its favor, the regulator called out that only 10% of the planned patient population has been treated so far.
The FDA also highlighted the lack of response duration data and “difficulty in interpreting progression-free survival data due to lack of prespecification for this analysis” as reasons to disregard the added trial.
The FDA under the second Trump administration has accrued a reputation for rejections that catch companies off guard. Most of these decisions have been linked to outgoing director of the Center for Biologics Evaluation and Research, Vinay Prasad, M.D. However, Replimune’s first rejection for RP1 was pinned to Richard Pazdur, M.D., an agency veteran who was then leader of the Oncology Center of Excellence, according to a report from Stat.
But after briefly taking charge of the Center for Drug Evaluation and Research, Pazdur has since retired from the agency, and the rejection letter notes that Replimune’s second review was performed by a different team than the one that oversaw the first review.
Editor's note: This story was updated at 10:15 a.m. ET on April 13 with comment from Replimune and at 10:30 a.m. ET on April 14 with more layoff information.