FDA rejects J&J’s injectable version of Rybrevant, cites manufacturing issues

Johnson & Johnson announced that the FDA in a Complete Response Letter (CRL) has declined to approve a subcutaneous version of the company’s drug Rybrevant to treat patients with non-small cell lung cancer with epidermal growth factor receptor mutations.    

“The CRL is related to observations as part of a standard pre-approval inspection at a manufacturing facility,” J&J said in its announcement, while noting that the CRL is “unrelated to the product formulation, or the efficacy and safety data submitted in the regulatory application, and the FDA has not requested any additional clinical studies.”

Yusri Elsayed, J&J’s global therapeutic area head for oncology, Innovative Medicine, in a statement said that the company is “working closely with the FDA” to bring a fixed combination of amivantamab and recombinant human hyaluronidase for subcutaneous administration (SC amivantamab) to patients as quickly as possible and they are “confident” in their “path to resolution.”

While J&J did not disclose the specifics of the “observations” made in the CRL based on the FDA’s pre-approval inspection, a frequent cause of CRLs are citations for violations of current Good Manufacturing Practices (cGMP). These can include issues with facility maintenance, equipment qualifications, or inadequate control over the manufacturing process.

A total of 238 CRLs were issued by the FDA between 2017 and 2023, according to Pink Sheet, with the majority (45%) related to clinical deficiencies, followed by quality/manufacturing issues (30%), labeling concerns (20%), and bioequivalence problems (5%).