The FDA has rejected Replimune’s request for approval of RP1, adding the melanoma drug candidate to the list of assets to receive complete response letters from the new-look agency. Investors sent the biotech’s share price down 76% to below $3 in premarket trading.
Replimune filed for accelerated approval of RP1, a virus designed to kill cancer cells and turn the immune system against the tumor, on the strength of the phase 1/2 Ignyte trial. The study tested RP1 in combination with Bristol Myers Squibb’s checkpoint inhibitor Opdivo in 140 patients who had previously progressed on a PD-1 drug. Replimune reported an objective response rate of 32.9%.
The FDA reportedly found fault with the study. According to Replimune, the agency said the trial is not considered “an adequate and well-controlled clinical investigation that provides substantial evidence of effectiveness.” The FDA added that “the trial cannot be adequately interpreted due to the heterogeneity of the patient population,” Replimune said.
Officials also called out perceived issues with Replimune’s phase 3 confirmatory trial. The biotech said the FDA noted “items related to the confirmatory trial study design which need to be addressed, including contribution of components.” Replimune CEO Sushil Patel, Ph.D., expressed surprise and disappointment at the FDA’s ruling.
“The issues highlighted in the CRL were not raised by the agency during the mid- and late-cycle reviews. Additionally, we had also aligned on the design of the confirmatory study,” the CEO said in a statement.
Patel’s comments are reminiscent of Capricor Therapeutics’ response to its CRL earlier this month. Linda Marbán, Ph.D., CEO of Capricor, voiced surprise and disappointment at the CRL, explaining that her team had followed the guidance provided by the FDA at every stage from submission through inspection and review.
Replimune enrolled a broad population in Ignyte, including patients with different stages of disease and treatment histories. The decision resulted in a heterogeneous patient population, a feature that the FDA reportedly cited as a problem in the CRL. Patel has previously said the breadth of the study population was informed by talks with the FDA.
“The FDA gave us a lot of direction on what they wanted to see. One of the key things was to make sure that we had a real-world population, that we saw clinically meaningful activity across subgroups,” Patel said at a Goldman Sachs event last year.
Replimune plans to request a meeting with the FDA and to urgently interact with the agency to find a path forward. Without timely accelerated approval of RP1, the biotech said the development of the drug candidate for advanced cancer patients with limited options will not be viable.
The company ended March with $483.8 million to its name. Talking on an earnings call in May, Patel said he expected the RP1 confirmatory trial to “take a couple of years to complete enrollment given the study population and size of the study.”