Janssen Gains FDA Approval for Subcutaneous Rybrevant Faspro Across All NSCLC Indications

Biologics manufacturers tracking route-of-administration bridging strategies have a new regulatory reference point: Janssen Biotech secured FDA approval on December 17, 2025 for amivantamab and hyaluronidase-lpuj (Rybrevant Faspro) for subcutaneous injection, covering all adult indications previously approved for the intravenous formulation of amivantamab (Rybrevant).

The approval rests on data from PALOMA-3, a randomized, open-label, multicenter trial enrolling 418 adults with locally advanced or metastatic non-small cell lung cancer harboring EGFR-exon 19 deletions or exon 21 L858R substitution mutations. Patients were randomized 1:1 to subcutaneous amivantamab plus lazertinib or intravenous amivantamab plus lazertinib. PK comparability was the central regulatory question: at the every-two-week dosage, the geometric mean ratio for Cycle 2 AUC was 1.03 (90% CI: 0.98–1.09), and steady-state Ctrough GMR reached 1.43 (90% CI: 1.27–1.61), with all lower confidence bounds clearing the pre-specified 0.8 comparability threshold.

For QA and regulatory leads building analogous IV-to-SC data packages, the PK bridging construct here is instructive. Descriptive analyses showed no notable differences in overall response rate or progression-free survival between arms, and no detrimental signal on overall survival, supporting the conclusion that the SC formulation does not compromise clinical outcomes relative to the IV reference.

The safety profile of the subcutaneous arm was broadly consistent with the IV arm, with one operationally significant divergence: systemic administration-related reactions occurred in 13% of patients receiving subcutaneous amivantamab versus 66% infusion-related reactions in the IV arm. For site-of-care planning and nursing protocol development, that differential carries direct workflow implications. The prescribing information retains warnings for hypersensitivity and administration-related reactions, interstitial lung disease/pneumonitis, venous thromboembolic events with concomitant lazertinib use, dermatologic adverse reactions, ocular toxicity, and embryo-fetal toxicity.

The review was conducted under Project Orbis, the FDA Oncology Center of Excellence framework for concurrent multinational oncology submissions, with the Australian Therapeutic Goods Administration and Health Canada participating. Reviews at those agencies may still be ongoing. Janssen also submitted an Assessment Aid to facilitate FDA's review process.

Full prescribing information for Rybrevant Faspro, including weight-based dosing tables specific to each indication, will be posted to Drugs@FDA; manufacturers and formulary teams should treat that document as the authoritative reference for dosing algorithm implementation.

Source: FDA Drugs, What's New RSS Feed via fda.gov, December 17, 2025; article indexed November 7, 2026.