Johnson & Johnson announced that the U.S. Food and Drug Administration (FDA) has approved RYBREVANT FASPRO™ (amivantamab and hyaluronidase-lpuj). It is the first and only subcutaneous treatment for patients who have EGFR-mutated non-small cell lung cancer (NSCLC). This also expands the indications of intravenous (IV) RYBREVANT®. This approval marks a significant advance in patient comfort and care delivery as the subcutaneous formulation decreases administration time from many hours to about 5 minutes. It also substantially lowers treatment burden for patients and healthcare systems. RYBREVANT FASPRO™ showed a roughly fivefold reduction in administration-related reaction (13% vs 66%) and a lower incidence of venous thromboembolism. It also maintains a safety profile consistent with the established IV regimen.
The approval is mainly supported by results from the Phase 3 PALOMA-3 study, which confirmed pharmacokinetic equivalence between subcutaneous and IV amivantamab. It showed that subcutaneous formulation delivered comparable or improved clinical results. Data presented at the 2024 American Society of Clinical Oncology meeting and published in the Journal of Clinical Oncology indicated longer time of response, improved progression-free survival, and higher overall survival for patients getting subcutaneous treatment, specifically when combined with LAZCLUZE® (lazertinib). In this study, median overall survival was higher in the subcutaneous arms, with 65% of patients alive at 12 months as compared with 51% in the IV arm, which highlights the clinical relevance of the new formulation.
The approval of RYBREVANT FASPRO™ builds on the strong survival benefit, as earlier shown in the Phase 3 MARIPOSA study. RYBREVANT® combined with LAZCLUZE® significantly decreased the risk of death as compared with Osimertinib in first-line treatment of patients with EGFR exon 19 deletions or L858R substitution mutations. Overall survival in the combination arm has not yet been reached with a median follow-up of about 38 months. Experts highlight that this chemotherapy-free regimen changes the biology of the disease by preventing or delaying resistance by a triple mechanism of action: dual targeting of EGFR, inhibition of MET signaling, and immune system engagement.
Additional MARIPOSA studies showed a significantly lower rate of acquired resistance mechanisms, like MET amplification and secondary EGFR mutations, as compared with osimertinib alone. It supports the durability of the benefits observed with the combination. Adverse reactions like rash, nail toxicity, musculoskeletal pain, edema, fatigue, gastrointestinal symptoms, and ocular effects remain common. The overall safety profile of RYBREVANT FASPRO™ is consistent with known risks of amivantamab-based therapy and is manageable with proper monitoring and supportive care. Subcutaneous administration was linked with fewer administration-related reactions and a lower rate of treatment interruptions. Prophylactic anticoagulation significantly reduced venous thromboembolic events.
Johnson & Johnson highlighted that comprehensive patient access and support programs, including RYBREVANT withMe, are available to help patients navigate insurance coverage, reimbursement, and cost support while providing individualized care navigation. RYBREVANT® itself is a first-in-class, fully human bispecific antibody targeting both EGFR and MET and is now approved across multiple treatment settings in EGFR-mutated NSCLC, including first-line and later-line indications, as monotherapy or in combination with lazertinib or chemotherapy.
The FDA approval of RYBREVANT FASPRO™ introduces a more patient-centered treatment option that maintains robust efficacy while dramatically simplifying administration, reinforcing a shift toward therapies that not only extend survival for patients with EGFR-mutated NSCLC but also improve quality of life, comfort, and dignity during treatment.
Reference: Johnson & Johnson. U.S. FDA Approval of RYBREVANT FASPRO™ (amivantamab and hyaluronidase-lpuj) enables the simplest, shortest administration time for a first-line combination regimen when combined with LAZCLUZE® (lazertinib). Johnson & Johnson Investor News. Published December 17, 2025. U.S. FDA Approval of RYBREVANT FASPRO™ (amivantamab and hyaluronidase-lpuj) Enables the Simplest, Shortest Administration Time for a First-Line Combination Regimen when Combined with LAZCLUZE® (lazertinib)
