FDA Approves Janssen’s Darzalex Faspro to Treat Newly Diagnosed AL Amyloidosis

Rare Daily Staff

The U.S. Food and Drug Administration granted accelerated approval to Janssen Biotech’s Darzalex Faspro for use in the treatment of adult patients with newly diagnosed light-chain amyloidosis.

Amyloidosis is a disease that occurs when amyloid proteins, which are abnormal proteins, accumulate in tissues and organs. When the amyloid proteins cluster together, they form deposits that damage the tissues and organs. Light-chain (AL) amyloidosis most frequently affects the heart, kidneys, liver, nervous system and digestive tract. Until now there were no approved therapies for AL amyloidosis in the United States, though it is currently being treated with chemotherapy, dexamethasone, stem cell transplants and supportive therapies. It is estimated that there are approximately 3,000 to 4,000 new cases of AL amyloidosis diagnosed annually in the U.S.

Darzalex Faspro is a subcutaneous formulation of daratumumab, in combination with a standard chemotherapy regimen of bortezomib, cyclophosphamide, and dexamethasone. Janssen Biotech developed it under a 2012 global license agreement with Danish biotech Genmab, initially as a treatment for multiple myeloma, for which it was approved in the U.S. in May 2020 and in Europe in June 2020.

A supplemental Biologics License Application for AL amyloidosis was submitted in September 2020. The U.S. FDA reviewed the submission of data for approval in this indication under their Real-Time Oncology Review pilot program and Project Orbis2. Continued approval may be contingent upon verification and description of clinical benefit in a confirmatory trial.

Daratumumab is a human IgG1k monoclonal antibody that binds with high affinity to the CD38 molecule, which is highly expressed on the surface of multiple myeloma cells. Daratumumab triggers a person’s own immune system to attack the cancer cells, resulting in rapid tumor cell death through multiple immune-mediated mechanisms of action and through immunomodulatory effects, in addition to direct tumor cell death, via apoptosis.

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

The approval was based on data from the Phase 3 ANDROMEDA study of daratumumab and hyaluronidase-fihj in combination with dexamethasone as treatment for patients with newly diagnosed AL amyloidosis.

“AL amyloidosis is a devastating and potentially fatal blood disorder that, until now, did not have any U.S. FDA-approved therapies,” said Jan van de Winkel, CEO of Genmab. “This makes today’s approval of Darzalex Faspro is a critical step forward for patients in the U.S. in dire need of treatment options.”

The approval was based on data from the Phase 3 ANDROMEDA study of daratumumab and hyaluronidase-fihj in combination with dexamethasone as treatment for patients with newly diagnosed AL amyloidosis.

The phase 3 study included 388 patients newly diagnosed with AL amyloidosis. Patients were randomized to receive treatment with either daratumumab and hyaluronidase-fihj in combination with bortezomib (a proteasome inhibitor), cyclophosphamide (a chemotherapy), and dexamethasone (a corticosteroid) or treatment with dexamethasone alone. The primary endpoint of the study was the percentage of patients who achieve hematologic complete response.

Patients treated with Darzalex Faspro in combination with standard chemotherapy had a 53 percent hematologic response rate compared to 18 percent for patients treated with chemotherapy alone.

The most common adverse reactions (≥20 percent) were upper respiratory tract infection, diarrhea, peripheral edema, constipation, fatigue, peripheral sensory neuropathy, nausea, insomnia, dyspnea and cough. Serious adverse reactions occurred in 43% of patients who received Darzalex Faspro in combination with dexamethasone.

Photo: Jan van de Winkel, CEO of Genmab