FDA Delays Approval of J&J's Subcutaneous Rybrevant for Lung Cancer Treatment
核心洞察
The FDA has declined to approve Johnson & Johnson's subcutaneous formulation of Rybrevant (amivantamab) for non-small cell lung cancer (搜索) due to manufacturing facility inspection issues.
The rejection was based on a Complete Response Letter citing issues found during a standard pre-approval inspection, unrelated to the drug's formulation or efficacy/safety data.
Clinical data from the Phase III PALOMA-3 trial demonstrated the subcutaneous injection was non-inferior to the intravenous formulation, with a five-fold reduction in infusion-related reactions.
The FDA has delayed the approval of Johnson & Johnson's (J&J) subcutaneous formulation of Rybrevant (amivantamab) for the treatment of certain patients with non-small cell lung cancer (搜索) (NSCLC). The decision follows a Complete Response Letter issued by the FDA, citing issues identified during a standard pre-approval inspection of a manufacturing facility.
The FDA's concerns do not relate to the drug's formulation or the efficacy and safety data packages submitted by J&J. The existing intravenous formulation of Rybrevant remains approved and available for use.
PALOMA-3 Trial Results
The application for subcutaneous Rybrevant was based on data from the Phase III PALOMA-3 trial. The study demonstrated that the subcutaneous injection was non-inferior to the intravenous formulation. 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. 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 trial also highlighted a significant reduction in infusion-related reactions with the subcutaneous formulation, showing a five-fold decrease compared to the intravenous administration.
Rybrevant's Mechanism of Action and Existing Approvals
Rybrevant is a bispecific antibody targeting both EGFR (搜索) and MET proteins, inhibiting tumor growth and enhancing immune system activity against cancer cells. It initially received accelerated approval in May 2021 for NSCLC patients with EGFR exon 20 insertion mutations who had progressed after platinum chemotherapy. In March, Rybrevant received traditional approval in combination with carboplatin and pemetrexed as a first-line treatment for NSCLC patients with EGFR exon 20 mutations. Furthermore, the FDA approved Rybrevant in combination with Lacluze for first-line treatment of locally advanced or metastatic NSCLC in August.
J&J's Response
"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," said Yusri Elsayed, Global Oncology Therapeutic Area Head at J&J Innovative Medicine, in a statement. J&J is actively addressing the manufacturing issues identified by the FDA to facilitate the approval of the subcutaneous formulation.