FDA grants traditional approval to daratumumab and hyaluronidase-fihj for newly diagnosed light chain amyloidosis
Regulatory approval: On Nov 19, 2025, the FDA granted traditional approval to subcutaneous daratumumab and hyaluronidase-fihj (Darzalex Faspro) with bortezomib/cyclophosphamide/dexamethasone (VCd) for newly diagnosed light chain (AL) amyloidosis. The indication previously received accelerated approval in 2021. Approval was supported by ANDROMEDA, showing improved MOD-PFS (HR 0.47) and overall survival (HR 0.62) versus VCd alone after 61.4 months’ median follow-up.
FDA traditional approval in newly diagnosed AL amyloidosis
Event type: Regulatory approval
Date: 2025-11-19
On November 19, 2025, the FDA granted traditional approval to daratumumab and hyaluronidase-fihj (Darzalex Faspro; Janssen Biotech Inc.) in combination with bortezomib, cyclophosphamide, and dexamethasone (VCd) for newly diagnosed light chain (AL) amyloidosis. The FDA had previously granted accelerated approval for this indication in 2021.
Key efficacy evidence (ANDROMEDA; NCT03201965)
Approval was supported by ANDROMEDA, an open-label, randomized, active-controlled trial enrolling 388 patients with newly diagnosed AL amyloidosis with measurable disease and ≥1 affected organ (per consensus criteria). Patients were randomized to VCd or daratumumab + VCd (D-VCd).
Endpoints supporting approval included major organ deterioration progression-free survival (MOD-PFS) and overall survival (OS). After median follow-up 61.4 months:
- MOD-PFS: HR 0.47 (95% CI, 0.33–0.67; p < 0.0001); median not reached with D-VCd vs 30.2 months with VCd.
- OS: HR 0.62 (95% CI, 0.42–0.90; p = 0.0121); median OS not reached in either arm.
Label safety and dosing highlights
Prescribing information includes warnings/precautions for cardiac toxicity, hypersensitivity and other administration reactions, neutropenia, thrombocytopenia, embryo-fetal toxicity, and interference with cross-matching and RBC antibody screening. Darzalex Faspro is not indicated/recommended for patients with NYHA IIIB/IV cardiac disease or Mayo stage IIIB outside controlled clinical trials. Recommended dosing is 1,800 mg daratumumab + 30,000 units hyaluronidase-fihj SC (abdomen) over ~3–5 minutes per schedule with VCd.