Cutaneous squamous cell carcinoma that doesn’t reply to therapy with an immunotherapy referred to as a checkpoint inhibitor has no FDA-approved therapeutic options. Replimune’s lead program, an oncolytic virus, has fallen brief in a examine hoped to present sufferers one. The corporate continues to be urgent ahead with its engineered virus in different sorts of pores and skin most cancers, however not with no pipeline shakeup meaning the top for different packages.
Replimune’s lead therapeutic candidate, RP1, is predicated 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 also be meant to immediate a further immune response towards the most cancers.
The outcomes introduced Tuesday are from a Part 2 scientific trial that the Woburn, Massachusetts-based firm hoped could be a registrational examine. A complete of 211 sufferers with cutaneous squamous cell carcinoma had been randomly assigned to obtain RP1 plus the Regeneron Prescription drugs checkpoint inhibitor Libtayo, or Libtayo alone. The 2 most important examine objectives had been assessing the entire response charge and the general response charge.
Replimune stated the examine drug arm achieved a whole response charge of 38.1% versus 25% within the management arm—simply in need of statistical significance. The general response charge outcomes had been nearer: 52.5% within the examine drug arm versus 51.4% within the Libtayo-alone group. One attainable rationalization for the disappointing outcomes is an imbalance in tumor burden at baseline throughout the therapy teams, which Replimune stated “might have impacted the variety of responses seen.”
Specifically, Replimune stated a considerably higher variety of sufferers with a excessive tumor burden (bigger than 10 cm in diameter) at baseline had been handled within the examine 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 stated this scientific trial will proceed with a view to assess the period of response, progression-free survival, and general survival.
In a word despatched to buyers Tuesday, Leerink Companions analyst Jonathan Chang wrote that the entire response charge outcomes counsel the trial final result would have been constructive with a extra strong examine design. He stated the outcomes are a significant setback for RP1, although the longer term readout of extra knowledge affords the chance to salvage this program in cutaneous squamous cell carcinoma.
Chang additionally stated RP1 has a possibility in melanoma, the place the info look higher up to now. The Part 2 take a look at is evaluating RP1 in sufferers whose illness has failed to answer therapy with a checkpoint inhibitor. This examine evaluated the pairing of RP1 with the Bristol Myers Squibb immunotherapy Opdivo. Replimune stated 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 consequence will assist a regulatory submission, which it plans to file within the second half of 2024.
In response to Replimune’s telling of a current 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 examine, which the FDA desires Replimune to start out by the point it information an utility in search of accelerated approval.
The Replimune pipeline additionally consists of RP2 and RP3, oncolytic viruses engineered to reinforce anti-tumor responses and tackle extra tumor varieties. The corporate is planning a randomized managed scientific take a look at of RP2 as a second-line therapy in uveal melanoma. To take care of deal with this scientific trial and the others deemed precedence research, Replimune stated 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 scientific trial will proceed with RP2 solely. Growth of RP3 can be discontinued.
Replimune reported a money place totaling $496.8 million as of the top 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 through the Nationwide Most cancers Institute
