Cutaneous squamous cell carcinoma that doesn’t reply to remedy with an immunotherapy referred to as a checkpoint inhibitor has no FDA-approved therapeutic alternate options. Replimune’s lead program, an oncolytic virus, has fallen brief in a research hoped to provide sufferers one. The corporate continues to be urgent ahead with its engineered virus in different varieties of pores and skin most cancers, however not with out a 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 supposed to immediate a further immune response in opposition to the most cancers.
The outcomes introduced Tuesday are from a Section 2 scientific trial that the Woburn, Massachusetts-based firm hoped can be a registrational research. A complete of 211 sufferers with cutaneous squamous cell carcinoma have been randomly assigned to obtain RP1 plus the Regeneron Prescribed drugs checkpoint inhibitor Libtayo, or Libtayo alone. The 2 important research objectives have been assessing the entire response price and the general response price.
Replimune stated the research drug arm achieved an entire response price of 38.1% versus 25% within the management arm—simply in need of statistical significance. The general response price outcomes have been nearer: 52.5% within the research 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 remedy teams, which Replimune stated “might have impacted the variety of responses seen.”
Particularly, Replimune stated a considerably higher variety of sufferers with a excessive tumor burden (bigger than 10 cm in diameter) at baseline have been handled within the research drug group in comparison with the group given Libtayo alone. In sufferers with a decrease complete tumor burden, the entire response price 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 in an effort to assess the period of response, progression-free survival, and general survival.
In a notice despatched to buyers Tuesday, Leerink Companions analyst Jonathan Chang wrote that the entire response price outcomes counsel the trial final result would have been optimistic with a extra strong research design. He stated the outcomes are a serious setback for RP1, although the longer term readout of further knowledge gives 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 thus far. The Section 2 take a look at is evaluating RP1 in sufferers whose illness has failed to answer remedy with a checkpoint inhibitor. This research 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 keeping with Replimune’s telling of a latest assembly with the FDA, the company acknowledged that sufferers whose melanoma has failed to answer remedy 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 begin by the point it recordsdata an software searching for accelerated approval.
The Replimune pipeline additionally contains 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 remedy in uveal melanoma. To take care of deal with this scientific trial and the others deemed precedence research, Replimune stated it’ll discontinue improvement of RP2 and RP3 in squamous cell carcinoma of the top and neck and colorectal most cancers. A second-line hepatocellular carcinoma scientific trial will proceed with RP2 solely. Growth of RP3 shall 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’ll have sufficient money to final into early 2026.
Public area picture by Julio C. Valencia by way of the Nationwide Most cancers Institute
