Cutaneous squamous cell carcinoma that doesn’t reply to therapy with an immunotherapy known as a checkpoint inhibitor has no FDA-approved therapeutic options. Replimune’s lead program, an oncolytic virus, has fallen quick in a research hoped to present sufferers one. The corporate remains to be urgent ahead with its engineered virus in different sorts of pores and skin most cancers, however not with out a pipeline shakeup meaning the tip for different packages.
Replimune’s lead therapeutic candidate, RP1, relies on based mostly on a pressure of the herpes simplex virus engineered to extend its anti-tumor exercise. Injected right into a stable tumor, replication of the virus kills most cancers cells. This oncolytic virus can be meant to immediate an extra immune response in opposition to the most cancers.
The outcomes introduced Tuesday are from a Section 2 medical trial that the Woburn, Massachusetts-based firm hoped could be a registrational research. A complete of 211 sufferers with cutaneous squamous cell carcinoma had been randomly assigned to obtain RP1 plus the Regeneron Prescribed drugs checkpoint inhibitor Libtayo, or Libtayo alone. The 2 major research targets had been assessing the entire response charge and the general response charge.
Replimune mentioned the research drug arm achieved a whole response charge of 38.1% versus 25% within the management arm—simply wanting attaining statistical significance. The general response charge outcomes had been nearer: 52.5% within the research drug arm versus 51.4% within the Libtayo-alone group. One doable rationalization for the disappointing outcomes is an imbalance in tumor burden at baseline throughout the therapy teams, which Replimune mentioned “might have impacted the variety of responses seen.”
Specifically, Replimune mentioned a considerably larger variety of sufferers with a excessive tumor burden (bigger than 10 cm in diameter) at baseline had been handled within the research drug group in comparison with the group given Libtayo alone. In sufferers with a decrease whole tumor burden, the entire response charge in sufferers handled with RP1 and Libtayo confirmed a lot clearer separation in comparison with these given Libtayo alone. Replimune mentioned this medical trial will proceed with a view to assess the period of response, progression-free survival, and total survival.
In a notice despatched to buyers Tuesday, Leerink Companions analyst Jonathan Chang wrote that the entire response charge outcomes counsel the trial consequence would have been optimistic with a extra strong research design. He mentioned the outcomes are a serious setback for RP1, although the long run readout of further knowledge gives the chance to salvage this program in cutaneous squamous cell carcinoma.
Chang additionally mentioned RP1 has a possibility in melanoma, the place the info look higher up to now. The Section 2 take a look at is evaluating RP1 in sufferers whose illness has failed to answer therapy with a checkpoint inhibitor. This research evaluated the pairing of RP1 with the Bristol Myers Squibb immunotherapy Opdivo. Replimune mentioned that within the full 140-patient cohort of sufferers whose most cancers failed to answer a checkpoint inhibitor, about 1 in 3 sufferers handled with the RP1/Opdivo mixture achieved a sturdy response. The corporate believes this outcome will assist a regulatory submission, which it plans to file within the second half of 2024.
Based on Replimune’s telling of a latest assembly with the FDA, the company acknowledged that sufferers whose melanoma has failed to answer therapy with an anti-PD1 checkpoint inhibitor represents an unmet want. Settlement was reached on the design of a confirmatory research, which the FDA needs Replimune to start out by the point it recordsdata an software looking for accelerated approval.
The Replimune pipeline additionally consists of RP2 and RP3, oncolytic viruses engineered to reinforce anti-tumor responses and deal with extra tumor sorts. The corporate is planning a randomized managed medical take a look at of RP2 as a second-line therapy in uveal melanoma. To keep up deal with this medical trial and the others deemed precedence research, Replimune mentioned it would discontinue growth of RP2 and RP3 in squamous cell carcinoma of the pinnacle and neck and colorectal most cancers. A second-line hepatocellular carcinoma medical trial will proceed with RP2 solely. Improvement of RP3 will probably be discontinued.
Replimune reported a money place totaling $496.8 million as of the tip of September. With the pipeline reprioritization, the corporate expects it would have sufficient money to final into early 2026.
Public area picture by Julio C. Valencia by way of the Nationwide Most cancers Institute