The FDA ( U.S. Food and Drug Administration ) has approved Darzalex Faspro ( Daratumumab and Hyaluronidase-fihj ), a subcutaneous formulation of Daratumumab, in combination with Bortezomib, Cyclophosphamide and Dexamethasone ( D-VCd ) for the treatment of adult patients with newly diagnosed light chain ( AL ) amyloidosis.
Darzalex Faspro is the first and only FDA-approved treatment for patients with this blood cell disorder that is associated with the production of an abnormal protein, which leads to the deterioration of vital organs, most notably the heart, kidneys and liver.
This indication is approved under accelerated approval and is based on the hematologic complete response rate ( hemCR ) measure. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.
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 FDA approval is based on positive results from the phase 3 ANDROMEDA study, which were presented at the American Society of Hematology ( ASH ) 2020 Annual Meeting.
The study has evaluated Darzalex Faspro in combination with VCd, compared with VCd alone, a common treatment regimen used in adult patients with newly diagnosed AL amyloidosis.
Patients receiving treatment with Darzalex Faspro has experienced a hemCR more than triple that of patients receiving VCd alone ( 42% for D-VCd and 13% for VCd; P inferiore a 0.0001 ).
Approximately 4,500 people in the U.S. develop this rare disease each year. AL amyloidosis is a life-threatening blood cell disorder that occurs when blood plasma cells in the bone marrow produce amyloid deposits, which build up in vital organs and eventually cause organ deterioration.
The disease can affect different organs in different people, but the most frequently affected organs are the heart, kidneys, liver, spleen, gastrointestinal tract and nervous system.
About one-third of patients visit five or more doctors before receiving a diagnosis, and 72% are diagnosed more than one year after they first experience symptoms.
Patients often have a poor prognosis due to the delay in diagnosis of AL amyloidosis, which frequently presents with non-specific symptoms that can mimic other, more common conditions.
As many as 30% of patients with AL amyloidosis die within the first year after diagnosis.
The most common adverse reactions ( 20% or more ) 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 have received Darzalex Faspro in combination with VCd.
Serious adverse reactions that occurred in at least 5% of patients in the D–VCd arm were pneumonia ( 9% ), cardiac failure ( 8% ) and sepsis ( 5% ).
Fatal adverse reactions occurred in 11% of patients. Fatal adverse reactions that occurred in more than one patient included cardiac arrest ( 4% ), sudden death ( 3% ), cardiac failure ( 3% ) and sepsis ( 1% ).
Among patients who received Darzalex Faspro in combination with VCd, 72% of patients had baseline cardiac involvement with Mayo Cardiac Stage I ( 3% ), Stage II ( 46% ) and Stage III ( 51% ).
Serious cardiac disorders occurred in 16% of patients ( 8% of patients with Mayo Cardiac Stage I and II and 28% of patients with Stage III ).
Serious cardiac disorders in more than 2% of patients included cardiac failure ( 8% ), cardiac arrest ( 4% ) and arrhythmia ( 4% ).
Fatal cardiac disorders occurred in 10% of patients ( 5% of patients with Mayo Cardiac Stage I and II and 19% of patients with Stage III ) who received Darzalex Faspro in combination with VCd.
Fatal cardiac disorders that occurred in more than one patient in the D-VCd arm included cardiac arrest ( 4% ), sudden death ( 3% ) and cardiac failure ( 3% ). ( Xagena )
Source: Janssen, 2021