FDA

Darzalex Faspro granted traditional approval for newly diagnosed light chain amyloidosis

November 26, 2025

On November 19, 2025, FDA granted traditional approval to Darzalex Faspro (daratumumab and hyaluronidase-fihj) with bortezomib, cyclophosphamide, and dexamethasone (VCd) for newly diagnosed light chain (AL) amyloidosis. The agency granted accelerated approval for this indication in 2021.

Efficacy

Efficacy was evaluated in the open-label, randomized, active-controlled ANDROMEDA trial (NCT03201965) involving 388 patients with newly diagnosed AL amyloidosis with measurable disease and at least one affected organ according to consensus criteria. Patients were randomized to receive bortezomib, cyclophosphamide, and dexamethasone (VCd) or Darzalex Faspro with VCd (D-VCd).

Approval was based on major organ deterioration progression free survival (MOD-PFS; defined as the duration from the date of randomization to either hematologic progression, major organ deterioration, or death, whichever occurred first), and overall survival (OS). After a median follow-up of 61.4 months, the trial showed an improvement in MOD-PFS in the D-VCd arm vs. the VCd arm (hazard ratio [HR], 0.47; 95% confidence interval [CI], 0.33-0.67; p-value <0.0001). Median MOD-PFS wasn’t reached in the D-VCd arm and was 30.2 months in the VCd arm. The trial also demonstrated an improvement in OS in the D-VCd arm vs. the VCd arm (HR, 0.62; 95% CI, 0.42-0.90; p-value 0.0121). Median OS hadn’t been reached in either arm.

Safety

The most common adverse reactions (≥20%) in patients with light chain (AL) amyloidosis are upper respiratory tract infection, diarrhea, peripheral edema, constipation, fatigue, peripheral sensory neuropathy, nausea, insomnia, dyspnea, and cough.

The prescribing information includes a warning for cardiac toxicity, stating that serious or fatal cardiac adverse reactions occurred in patients with light chain (AL) amyloidosis who received Darzalex Faspro in combination with VCd.

Darzalex Faspro is not indicated and is not recommended for the treatment of patients with light chain (AL) amyloidosis who have NYHA Class IIIB or Class IV cardiac disease or Mayo Stage IIIB outside of controlled clinical trials.

Recommended dose

The recommended dosage of Darzalex Faspro is 1,800 mg daratumumab and 30,000 units hyaluronidase-fihj administered SC into the abdomen over approximately 3 to 5 minutes according to the recommended schedule in combination with VCd.

Sources:

FDA grants traditional approval for daratumumab and hyaluronidase-fihj for newly diagnosed light chain amyloidosis. [News release]. 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-traditional-approval-daratumumab-and-hyaluronidase-fihj-newly-diagnosed-light-chain

Darzalex Faspro (daratumumab and hyaluronidase-fihj) [package insert]. Food and Drug Administration. https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/761145s032lbl.pdf Revised November 2025. Accessed November 25, 2025.