Issues at the former Catalent plant, now owned by Novo Nordisk, derailed another FDA application, Incyte announced Friday that the FDA has submitted a complete response letter (CRL) for its PD-1 inhibitor Zynyz as a first-line treatment for non-small cell lung cancer (NSCLC).
The failure (PDF) was not due to efficacy or safety concerns, but was related to test results at a fill-finish facility, specifically the former Catalent plant in Bloomington, Indiana, which is now owned by Novo as part of Novo Holdings’ $16.5 billion acquisition of CDMO in 2024.
This setback comes more than a year after Incyte detailed that Zynyz in combination with chemotherapy and chemotherapy alone reduced the risk of death by 25% in patients with newly diagnosed metastatic NSCLC in the Phase 3 POD1UM-304 trial.
By clearing that clinical hurdle, Incyte was poised to enter the lucrative first-line NSCLC market, but it is currently being stumbled by a manufacturing site that is causing headaches for several biopharmaceutical companies.
Incyte joins a growing list of drugmakers whose regulatory timelines have been delayed due to compliance issues at Novo’s Indiana location (referred to as Catalent Indiana in Incyte’s filings). Last year, the institution received a pair of CRLs for Regeneron, one for high-dose Eylea and one for the blood cancer bispecific odronestamab.
Scalar Rock also received a CRL last year thanks to production issues at the former Catalent plant, but its spinal muscular atrophy candidate apitegromab was denied approval in September.
Problems at the Indiana plant culminated in an FDA warning letter in November. During the summer 2025 inspection, FDA found that the facility had not adequately investigated more than 20 deviations related to potential contamination of drug products due to mammalian hair contamination in or around the vial stopper area.
The FDA issued a CRL to Insight on February 27th. On the same day, the FDA delivered another manufacturing-related CRL to Ferring Pharmaceuticals, affecting the company’s human recombinant follicle-stimulating hormone follitropin delta (FE 999049), which is being developed for women undergoing uncontrolled ovarian stimulation. The drug has been approved under the brand name Rekovelle in several international markets, including the European Union.
The Ferring issue does not appear to have come from the Catalent Indiana site. Although the Novo manufacturing facility’s censure is not related to a specific product, Ferring’s CRL resulted in an FDA Form 483 following deficiencies discovered during the facility’s prelicensure inspection, according to a CRL (PDF) issued by the FDA.
Fierce Pharma has contacted Mr. Ferring for comment.
With respect to Incyte, the CRL’s impact is limited. First-line NSCLC is the number one indication in oncology, but Merck’s deeply entrenched Keytruda leaves little room for the new PD-1 in most developed markets.
Zynyz received initial FDA approval last year, making it the first treatment specifically approved for first-line anal cancer. Incyte also announced Friday that the European Commission has approved similar uses of the drug.
Zynyz generated sales of $66.4 million last year following the acquisition decision in May 2025. Former Insight CEO Hervé Hoppenau previously told Fiers that the company does not expect PD-1 inhibitors to be a major revenue driver, but noted that the U.S. approval could be used as a reference by regulators in certain emerging markets.
