Krystal Biotech’s decision follows the FDA’s rejection last month of Replimune’s RP1, which works similarly to Krystal Biotech’s KB707. The biotech said this has introduced “heightened uncertainty” regarding a potential accelerated pathway for the candidate.
Krystal Biotech has discontinued a Phase I/II study of its investigational intratumoral therapy KB707, which the Pennsylvania-based company was advancing for the treatment of solid tumors, in particular melanoma.
This move comes after the FDA last month handed a surprise rejection to Replimune’s RP1, which works similarly to KB707. Both RP1 and KB707 are immunotherapies that use modified herpes simplex virus type 1 vectors to trigger an immune response against tumors. RP1 was also being developed for melanoma.
In its news release on Thursday, Krystal announced that it had suspended enrollment into the Phase I/II OPAL-1 study, though it continues to monitor patients who had already been dosed for safety and efficacy. Based on the findings of the trial, Krystal “may adjust development plans” for intratumoral KB707. “Heightened uncertainty regarding potential accelerated approval pathways” for KB707 following the FDA’s rejection of RP1 contributed to the biotech’s decision, Stéphane Paquette, Krystal’s vice president for corporate development, told STAT News.
The FDA’s rejection of RP1 was controversial. Earlier this month, both Endpoints News and STAT reported that Richard Pazdur, director of the FDA’s Oncology Center of Excellence and acting director of the Office on Oncology Diseases, overruled agency reviewers and pushed for the candidate’s rejection.
Shortly after the rejection, scientists who helped design and run Replimune’s Phase III IGNYTE trial urged the FDA to re-review the application. In an open letter signed by more than 20 melanoma and cancer experts, researchers addressed concerns that the agency raised in its complete response letter. For example, the experts argued that one issue cited by FDA reviewers, the heterogeneity of IGNYTE’s patient population, in fact provided a more accurate representation of the real-world scenario than a more uniform population would have.
Melanoma treatment guidelines currently in place “show multiple treatment pathways in both the adjuvant and advanced disease setting funneling to the point of IGNYTE eligibility,” they wrote.
Now, with intratumoral KB707 all but deprioritized, Krystal is turning its focus to an inhaled version of the drug, which it is developing for non-small cell lung cancer (NSCLC). The biotech announced on Thursday that it had been granted an End of Phase II meeting with the FDA following “promising early evidence of efficacy” of the candidate.
A readout in June showed that inhaled KB707 elicited an objective response rate of 36% in heavily pretreated NSCLC patients, while median duration of response and progression-free survival were not reached. There were no grade 4 or 5 adverse events.
The regulatory meeting is scheduled for October and will help Krystal determine potential pathways for bringing inhaled KB707 forward.
