FDA Issues Complete Response Letter for J&J's Subcutaneous Rybrevant BLA in EGFR-Mutated NSCLC

Key Insights

• The FDA issued a Complete Response Letter (CRL) to Johnson & Johnson's Biologics License Application (BLA) for subcutaneous Rybrevant to treat EGFR-mutated non-small cell lung cancer (NSCLC).
• The CRL was a result of the FDA's standard pre-approval inspection at a manufacturing facility, and is not related to the product formulation, efficacy, or safety data.
• Rybrevant, an EGFR/MET inhibitor, is already approved in an intravenous formulation for NSCLC, and the BLA sought approval for a fixed combination of subcutaneous Rybrevant and recombinant human hyaluronidase.

Johnson & Johnson (J&J) has received a Complete Response Letter (CRL) from the FDA regarding its Biologics License Application (BLA) for a subcutaneous (SC) formulation of Rybrevant (amivantamab) intended for the treatment of EGFR-mutated non-small cell lung cancer (NSCLC). Rybrevant, a targeted therapy inhibiting both EGFR and MET, is currently approved as an intravenous (IV) formulation for various NSCLC treatment regimens.

The BLA sought approval for a fixed combination of SC Rybrevant and recombinant human hyaluronidase. The application was based on data derived from the Phase III PALOMA-3 study and had been granted Priority Review by the FDA in August.

CRL Details

According to J&J, the CRL was issued following a standard pre-approval inspection conducted by the FDA at a manufacturing facility. Importantly, the CRL is not related to the SC Rybrevant formulation itself, nor does it stem from concerns regarding the efficacy or safety data submitted within the regulatory application. Furthermore, the FDA has not requested any additional clinical studies related to this application.

Rybrevant's Expanding Approvals

Rybrevant has seen several approvals and recommendations recently for use in combination therapies. In August, the FDA approved Rybrevant in combination with the oral EGFR-TKI inhibitor Lazcluze (lazertinib) as a first-line, chemotherapy-free treatment option for adult patients with locally advanced or metastatic NSCLC harboring EGFR exon 19 deletions or exon 21 L858R substitution mutations. This approval was based on data from the Phase III MARIPOSA study, which compared the Rybrevant-Lazcluze combination against AstraZeneca’s Tagrisso (osimertinib).

In September, Rybrevant in combination with standard-of-care chemotherapy (carboplatin and pemetrexed) received FDA approval for the first-line treatment of patients with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations. This combination is also approved for a similar indication in the European Union. The Committee for Medicinal Products for Human Use (CHMP) has also recommended the approval of the Rybrevant-Lazcluze combination for a similar indication.