The FDA’s recent rebuff of Replimune’s melanoma candidate has rippled across the industry, prompting one biotech to shutter a clinical trial evaluating a similar drug.
Krystal Biotech has discontinued a phase 1/2 trial assessing intratumoral injections of KB707, a modified herpes simplex virus type 1-based gene therapy, for patients with advanced skin cancer.
The move impacts OPAL-1, an open-label, dose escalation and expansion study, according to an Aug. 21 release Krystal issued midday. Patients who have already been enrolled in the trial will continue to be followed, the company said.
Based on safety and efficacy results from the phase 1/2 study, Krystal said it may change its development plans for intratumoral KB707.
The company suspended enrollment because “a recent decision by the regulatory agency has signaled a shift in their approach to drug approvals,” according to a bulletin sent to participating physicians and obtained by Stat News.
A member of Krystal’s team told Stat that the decision was made, in part, because of the “heightened uncertainty regarding potential accelerated approval pathways” for KB707 after Replimune’s drug failed to secure approval.
Like Krystal’s drug, Replimune’s asset is delivered via injection and is engineered using the herpes virus. Both were also being studied in combination with Bristol Myers Squibb’s checkpoint inhibitor Opdivo, with Krystal testing KB707 in combination with Merck’s Keytruda as well.
In June, the FDA denied Replimune’s approval application, which leveraged phase 1/2 data from 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 trial. According to Replimune, the agency said the study wasn't “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 at the time.
The agency also called out perceived issues with Replimune’s phase 3 confirmatory trial.
“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,” Replimune CEO Sushil Patel, Ph.D., said in a statement last month.
The FDA decision has drawn widespread criticism, with the editorial board at The Wall Street Journal responding with a scathing opinion piece that claimed “therapies for rare and deadly disease are dying in Marty Makary’s shop.”
As for Krystal, the biopharma will continue to move forward with an inhaled version of KB707, according to the Aug. 21 release. The two formulations are the company’s only clinical cancer candidates, though the biopharma touts more advanced assets in ophthalmology and dermatology.
Krystal also sells Vyjuvek, the first approved topical gene therapy for wound treatment related to dystrophic epidermolysis bullosa (DEB), an inherited disease that causes the skin to easily blister and break.
Editor's note: This article was updated at 12:30 p.m. ET to include information from Krystal's release.