The FDA cited issues with a manufacturing facility as the reason for the rejection. J&J is currently “working closely” with the regulator to resolve these problems.
The FDA on Monday declined to approve Johnson & Johnson’s subcutaneous formulation of its bispecific antibody Rybrevant (amivantamab), which the pharma was proposing for the treatment of certain patients with non-small cell lung cancer.
In its Complete Response Letter, the regulator flagged issues detected during a standard pre-approval inspection of a manufacturer, according to J&J. The FDA did not raise concerns regarding product formulation or the company’s efficacy and safety data packages for subcutaneous Rybrevant. Monday’s rejection will also not affect Rybrevant’s existing approval as an intravenous therapy.
“We’re working closely with the FDA to bring [subcutaneous] amivantamab to patients as quickly as possible, and are confident in our path to resolution,” Yusri Elsayed, Global Oncology Therapeutic Area Head at J&J Innovative Medicine, said in a statement.
J&J is seeking approval for subcutaneous Rybrevant based on data from the Phase III PALOMA-3 trial, which in May found that the under-the-skin injection was non-inferior to the intravenous formulation. After a median follow-up of 17 months, patients dosed subcutaneously saw an overall response rate of 30%, versus 33% in comparators treated intravenously.
The PALOMA-3 readout, presented at the 2024 Annual Meeting of the American Society of Clinical Oncology, also showed that subcutaneous Rybrevant resulted in a longer duration of response, progression-free survival and overall survival than the intravenous formulation.
Rybrevant is a bispecific antibody that works by binding both the EGFR and MET proteins, thus suppressing tumor growth and facilitating the immune system’s anticancer activity. It was first approved in May 2021 under the FDA’s accelerated pathway, allowing its use for metastatic or locally advanced non-small cell lung cancer (NSCLC) patients harboring EGFR exon 20 insertions whose disease had progressed on or after platinum chemotherapy.
In March, the FDA granted Rybrevant traditional approval in combination with carboplatin and pemetrexed. At the time, J&J touted Rybrevant as the “first targeted approach approved for the first-line treatment” of NSCLC patients with EGFR exon 20 mutations.
A few months later, in August, Rybrevant cleared another regulatory hurdle when the FDA approved its combination with Lacluze, a brain-penetrant EGFR tyrosine kinase blocker, for the first-line treatment of locally advanced or metastatic NSCLC. The drug combo is the first multitargeted, chemotherapy-free regimen that has shown superiority versus AstraZeneca’s Tagrisso, J&J said at the time.
