Retifanlimab

The FDA has issued a complete response letter, rejecting Hyloris Pharmaceuticals' antiviral valacyclovir. Last month, the company said its manufacturing facility in Greece did not meet current good manufacturing practice standards according to the FDA. The FDA has rejected Hyloris Pharmaceuticals antiviral valacyclovir, an oral suspension for infections caused by herpes simplex and varicella zoster viruses. In a complete response letter (CRL), the FDA said it identified issues in an inspection of Hyloris’ third-party manufacturer. The U.S. regulator did not specify the problems in the CRL, explaining that they were itemized to a representative of the production facility.The CRL was not a surprise. In a release last month, Belgium-based Hyloris explained (PDF) that the FDA had assigned an official action indicated (OAI) classification to the Greek facility after an inspection. An OAI is the most severe of three FDA inspection classifications, indicating that the plant does not meet current good manufacturing practice (cGMP) standards and requires significant corrective actions.“The manufacturer has a well-established track record of pharmaceutical production and supply, serving multiple clients in regulated markets, including the U.S.,” Hyloris explained in February of the plant. “Following the inspection outcome, the manufacturer has paused the manufacturing of products destined for the U.S. while currently still producing oral dosage forms for markets outside of the U.S.”Hyloris added in February that it was working on a “manufacturing solution” for the product. The original target date for an FDA decision was in October. In the CRL, the FDA said it would need to conduct a cGMP inspection plus a preapproval inspection before approving its new drug application. Additionally, the CRL spelled out that Hyloris needed to provide more safety information from all clinical and nonclinical studies of valacyclovir in all the indications in which it has been tested.Three decades ago, GSK scored FDA approval of Valtrex, a tablet form of valacyclovir, for treating herpes zoster, with subsequent nods to include genital herpes and cold sores. It became available as a generic treatment in 2010. In 2022, the FDA rejected (PDF) another Hyloris candidate because of a packaging problem. A year later, the U.S. regulator signed off on Maxigesic IV, an intravenous post-surgery pain relief medicine. The FDA has sent out several manufacturing-related CRLs recently, including at least two on Feb. 27. One was to Ferring Pharmaceuticals for its human recombinant follicle stimulating hormone Rekovelle. Another was to Incyte for its PD-1 inhibitor Zynyz. The rejection was over inspection findings at its third-party fill-finish facility, a former Catalent plant in Bloomington, Indiana, which is now owned by Novo Nordisk. The massive plant has been cited in several CRLs over the last several months.

Incyte Corporation disclosed in a SEC filing dated March 6, 2026, that the US FDA issued a Complete Response Letter (CRL) on February 27, 2026, for the supplemental Biologics License Application for Zynyz (retifanlimab-dlwr) injection (375 mg). The sBLA sought approval for the treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) in combination with platinum-based chemotherapy. The application was supported by data from the Phase III POD1UM-304 trial, results of which were announced in December 2024. The CRL cited inspection findings in relation to the drug’s manufacturing site as the sole approvability issue, based on a visit to Catalent Indiana, LLC, a third-party fill-finish facility acquired first by Novo Holdings, and in the process of being transferred to Novo Nordisk. The FDA did not raise concerns regarding the efficacy or safety data supporting Zynyz in NSCLC, nor did it cite issues with the third-party drug substance manufacturer. The inspection findings at Catalent Indiana were not specific to Zynyz, indicating the manufacturing compliance matter extends beyond this particular product. Practically, the CRL means Incyte cannot receive approval for this indication until the facility-related issues are resolved to FDA’s satisfaction. Retifanlimab-dlwr is a humanized monoclonal antibody that binds to programmed death receptor-1, blocking its interaction with PD-L1 and PD-L2. This mechanism reactivates T-cell-mediated anti-tumor immune responses. Metastatic NSCLC remains one of the leading causes of cancer-related mortality, and PD-1 checkpoint inhibitors combined with platinum-based chemotherapy have become a standard first-line treatment approach. Several PD-1 and PD-L1 inhibitors, including pembrolizumab and nivolumab, are already approved in this setting. Retifanlimab’s entry would have added another option in a competitive but clinically relevant space. Retifanlimab originated at MacroGenics, Inc., where it was designated MGA012. In November 2017, Incyte entered a global collaboration and license agreement with MacroGenics, obtaining exclusive worldwide development and commercialization rights. MacroGenics received a USD 150 million upfront payment with eligibility for up to $760 million in additional milestones plus tiered royalties. Since that agreement, Incyte has held sole responsibility for regulatory strategy, clinical development, and commercialization. Zynyz received FDA accelerated approval in March 2023 for metastatic or recurrent locally advanced Merkel cell carcinoma, establishing its initial US market presence. The NSCLC sBLA represented Incyte’s effort to expand the label into a larger oncology population. The provided materials do not reference prior CRLs for this specific sBLA or for the original Merkel cell carcinoma BLA. No information was available regarding approvals of retifanlimab in other regulatory jurisdictions such as the EU or Japan. Incyte stated it is working with the FDA and Catalent Indiana to address the CRL and support a potential sBLA resubmission. The resolution timeline depends on Catalent Indiana’s ability to remediate the inspection findings and satisfy FDA requirements, a process over which Incyte has limited direct control. The company did not disclose a projected resubmission date or indicate whether alternative manufacturing arrangements are under consideration. Your email address will not be published. Required fields are marked * Comment * Name * Email * Website