FDA Grants Accelerated Approval to Darzalex Faspro for Newly Diagnosed Light Chain Amyloidosis

The U.S. Food and Drug Administration (FDA) has granted accelerated approval to daratumumab plus hyaluronidase (Darzalex Faspro, Janssen Biotech) in combination with bortezomib, cyclophosphamide and dexamethasone for newly diagnosed light chain (AL) amyloidosis.

Efficacy was evaluated in ANDROMEDA (NCT03201965), an open-label, randomized, active-controlled trial in 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 arm) or with Darzalex Faspro (D-VCd arm).

The hematologic complete response (HemCR) rate based on established consensus response criteria as evaluated by an independent review committee was 42.1% for the D-VCd arm and 13.5% for the VCd arm (odds ratio=4.8; 95% CI: 2.9, 8.1; p<0.0001).

The prescribing information includes a Warnings and Precautions that serious or fatal cardiac adverse reactions occurred in patients with light chain (AL) amyloidosis who received Darzalex Faspro in combination with bortezomib, cyclophosphamide and dexamethasone. 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.

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

The recommended Darzalex Faspro dose is (1,800 mg daratumumab and 30,000 units hyaluronidase) administered subcutaneously into the abdomen over approximately 3 to 5 minutes according to recommended schedule in combination with VCd.

This review was conducted under Project Orbis, an initiative of the FDA Oncology Center of Excellence. Project Orbis provides a framework for concurrent submission and review of oncology drugs among international partners. For this review, FDA collaborated with the Australian Therapeutic Goods Administration (TGA), the Brazilian Health Regulatory Agency (ANVISA), Health Canada, and Switzerland’s Swissmedic. ANVISA approved this application on November 30, 2020. The application reviews are ongoing at the other regulatory agencies.

This review used the Real-Time Oncology Review (RTOR) pilot program, which streamlined data submission prior to the filing of the entire clinical application, and the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment. The FDA approved this application 7 weeks ahead of the FDA goal date.

This application was granted accelerated approval based on response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).