NEW YORK – Johnson & Johnson earlier this week said it received a complete response letter from the US Food and Drug Administration for its biologics license application seeking approval of a fixed combination of Rybrevant (amivantamab) and recombinant hyaluronidase for subcutaneous administration in patients with non-small cell lung cancer harboring certain EGFR mutations.
The agency's denial is unrelated to the product's formulation or the efficacy and safety data that J&J submitted in its BLA, and the FDA has not requested any additional clinical data, according to the company. Instead, the complete response letter pertained to observations made during a standard pre-approval inspection at a manufacturing facility.
Rybrevant, an EGFR- and MET-targeted bispecific antibody, is approved in the US, Europe, and elsewhere as a single agent and in combination with chemotherapy for treating locally advanced or metastatic NSCLC harboring an EGFR exon 20 insertion mutation. The drug is also approved in combination with J&J's EGFR inhibitor Lazcluze (lazertinib) in first-line and in combination with chemotherapy for later-line treatment of advanced NSCLC with EGFR exon 19 deletions and exon 21 L858R substitution mutations. These currently approved indications for the intravenous formulation of Rybrevant are not affected by the complete response letter.
J&J submitted data from the Phase III PALOMA-3 clinical trial that compared subcutaneous Rybrevant combined with Lazcluze to intravenous Rybrevant and Lazcluze in patients with advanced or metastatic NSCLC harboring EGFR exon 19 deletions and exon 21 L858R substitution mutations, after progression on AstraZeneca's EGFR inhibitor Tagrisso (osimertinib) and chemotherapy, finding the subcutaneous Rybrevant regimen non-inferior.
"We're working closely with the FDA to bring [subcutaneous Rybrevant] to patients as quickly as possible, and are confident in our path to resolution," Yusri Elsayed, J&J's global therapeutic area head of oncology, innovative medicine, said in a statement. "We're proud to have helped so many patients in the front-line setting already with Rybrevant and look forward to further expanding treatment options with our subcutaneous formulation pending regulatory review and approval."