US FDA approves daratumumab combo for treating light chain amyloidosis

January 20, 2021 0 By FM

Johnson & Johnson’s subcutaneous formulation of the monoclonal antibody daratumumab and hyaluronidase-fihj (Darzalex Faspro) received the US FDA approval to treat light chain (AL) amyloidosis, a rare and often fatal blood cell disorder. The drug has been approved for use in combination with bortezomib, cyclophosphamide and dexamethasone.

AL amyloidosis is caused by a defect in bone marrow cells called plasma cells, causing them to produce abnormal forms of light chain proteins, which enter the bloodstream and form amyloid deposits. Amyloid plaques can then form in multiple organs such as the heart, kidneys and liver, damaging them and in some cases leading to organ failure. AL amyloidosis patients have had to rely on chemotherapy, with its accompanying side effects, and other drugs to tackle organ failure once the damage gets severe.

The recent approval was based on results of the randomized controlled phase 3 ANDROMEGA trial, which included 388 patients with light chain amyloidosis with measurable disease and at least one affected organ.

Researchers randomly assigned patients to bortezomib (Velcade, Takeda/Millennium), cyclophosphamide and dexamethasone (VCd)  with or without daratumumab plus hyaluronidase-fihj.

Patients treated with daratumumab plus hyaluronidase-fihj combination therapy saw a haematologic response rate that was nearly triple that of those treated with VCd alone, at 53% compared to 18%, respectively, noted the company. Being subcutaneously administrated, daratumumab plus hyaluronidase-fihj can be delivered in three to five minutes.

Results showed a higher hematologic complete response rate as assessed by independent review committee in the group assigned the experimental combination (42.1% vs. 13.5%)

Moreover, J&J’s drug seemed to limit the organ damage, improving measures of heart and kidney function after six months’ treatment and prolonging the time to major organ deterioration.

The most common adverse events of the combination included upper respiratory tract infection, diarrhoea, peripheral oedema, constipation peripheral sensory neuropathy, fatigue, nausea, insomnia, dyspnea and cough.