Replimune received a second FDA complete response letter for RP1 in advanced melanoma, raising questions about the viability of its oncolytic immunotherapy program.
Replimune Group received a complete response letter (CRL) from FDA for its biologics license application (BLA) seeking approval of RP1 in combination with nivolumab for advanced melanoma.
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The letter marks a significant regulatory setback for the company’s lead oncolytic immunotherapy program, and
RP1 is an engineered herpes simplex virus designed to enhance tumor cell killing and stimulate a systemic anti-tumor immune response through the expression of a fusogenic protein and GM-CSF.2
The therapy is being developed as part of a broader effort to expand the role of oncolytic immunotherapies in cancer treatment, particularly for patients who do not respond to checkpoint inhibitors.
The application is supported by data from
Replimune is pushing back on the agency’s decision, arguing that the same dataset had previously supported breakthrough therapy designation and should have been adequate for accelerated approval.1
“It is deeply disappointing that the FDA has not exercised regulatory flexibility to meet patients’ needs given the data supporting strong efficacy and the favorable safety profile,” said Sushil Patel, PhD, CEO of Replimune. “A treatment desperately needed by patients will not be available. Not because the medicine failed. Because the system did.”
The company also raised concerns about the regulatory review process, pointing to what it described as inconsistencies in agency feedback and communication.
According to Replimune, a new review team was assigned during the resubmission process, replacing the group that had previously engaged with the company.1 The new team did not meet with the company during the review, despite requests from the company.
Replimune continued to state that the CRL appeared to contradict prior FDA feedback, including discussions during earlier Type A and pre-BLA meetings. The company noted that the agency had previously indicated that a single-arm study could be sufficient for accelerated approval if the data were compelling and had not objected to a BLA based primarily on the Ignyte dataset.1
In addition, the FDA had accepted the resubmission as a complete response to an earlier CRL, raising expectations that the application was on a viable regulatory path.
The agency’s latest feedback included questions around trial design and tumor assessment methodology. Replimune emphasized that it had followed FDA guidance in using Recist 1.1 criteria and had provided additional analyses to address potential concerns, including evaluations of injected versus non-injected lesions and the impact of biopsies or surgical interventions on response outcomes.1
Replimune indicated that the regulatory setback is expected to have immediate operational implications for the company. Without
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