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FDA approves the first light chain amyloidosis drug
FDA approves the first light chain amyloidosis drug. FDA approval is based on the positive results of the phase 3 clinical trial ANDROMEDA (NCT03201965).
On January 15, 2021, Johnson & Johnson’s Janssen announced that the FDA has approved the daratumumab subcutaneous injection DARZALEX FASPRO® (daratumumab/hyaluronidase-fihj) in combination with bortezomib, cyclophosphamide and dexamethasone (D- VCd), to treat newly diagnosed adult patients with light chain (AL) amyloidosis.
DARZALEX FASPRO® has also become the only CD38 antibody approved for subcutaneous administration to treat multiple myeloma and light chain amyloidosis. Light chain amyloidosis is related to the production of abnormal proteins, which can lead to the deterioration of vital organs, especially the heart, kidneys, and liver. The approval of this indication is based on the hematology complete response rate (hemCR) indicator and is eligible for accelerated approval.
Approximately 4,500 people in the United States suffer from this rare disease each year. Light chain amyloidosis can be life-threatening, because plasma cells in the bone marrow produce amyloid deposits, which accumulate in vital organs and eventually lead to organ degradation. The disease can affect different organs in different people, but the most commonly affected organs are the heart, kidneys, liver, spleen, gastrointestinal tract, and nervous system. Due to delays in diagnosis, patients usually have a poor prognosis and often show non-specific symptoms similar to other common diseases. As many as 30% of patients with light chain amyloidosis die within the first year after diagnosis.
In August 2012, Janssen reached a global agreement with Genmab, granting Janssen an exclusive license to develop, produce and commercialize daratumumab. DARZALEX FASPRO® also contains recombinant human hyaluronidase PH20 (rHuPH20), using Halozyme’s ENHANZE® drug delivery technology.
The FDA approval is based on the positive results of the phase 3 clinical trial ANDROMEDA (NCT03201965). ANDROMEDA is a randomized, open-label phase 3 clinical study that evaluated DARZALEX FASPRO® in combination with bortezomib, cyclophosphamide, and dexamethasone (D-VCd). Compared with VCd alone, the treatment of newly diagnosed lighter The safety and effectiveness of adult patients with amyloidosis.
The study included 388 patients with detectable blood diseases and one or more organs affected. The primary endpoint is the hematological complete remission rate of intention-to-treat (ITT). Patients receive a subcutaneous injection of 1,800 mg/30,000 units of DARZALEX FASPRO® once a week from the 1st to the 8th week, every 2 weeks from the 9th to the 24th week, and every 4 weeks from the 25th week, until the disease progresses or becomes unhealthy. The accepted toxicity is up to 2 years. Among patients receiving D-VCd, 74% were treated for 6 months or longer, and 32% were treated for more than one year.
The results showed that the hemCR of patients treated with DARZALEX FASPRO® was more than 3 times that of VCd alone (D-VCd was 42%, VCd was 13%; P<0.0001).
The most common adverse reactions (≥20%) in the study 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 receiving DARZALEX FASPRO® and VCd combination therapy.
More than 5% of patients in the D-VCd group had serious adverse reactions including pneumonia (9%), heart failure (8%) and sepsis (5%). Fatal adverse reactions occurred in 11% of patients. Fatal adverse reactions in more than one patient included cardiac arrest (4%), sudden death (3%), heart failure (3%), and sepsis (1%).
(source:chinanet, reference only)