Darzalex Faspro (daratumumab and hyaluronidase-fihj) is the first subcutaneous therapy approved for the treatment of newly diagnosed light chain (AL) amyloidosis in adult patients.
Johnson & Johnson Innovative Medicine (formerly Janssen Biotech), the developer, was granted an exclusive global license to develop, manufacture and commercialise Darzalex (daratumumab) from Genmab in August 2012.
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Darzalex Faspro is available as a colourless to yellow and clear to opalescent solution containing 1,800mg of daratumumab and 30,000 units of hyaluronidase per 15ml, in a single-dose vial for subcutaneous administration, injected into the subcutaneous tissue of the abdomen.
Darzalex Faspro approvals
The US Food and Drug Administration (FDA) approved Darzalex Faspro (daratumumab and hyaluronidase-fihj) for the treatment of adult patients with multiple myeloma (MM) in May 2020.
The European Commission (EC) granted marketing authorisation for the same indication in June 2020.
The FDA granted accelerated approval for Darzalex Faspro in combination with bortezomib, cyclophosphamide, and dexamethasone (VCd) in January 2021 and subsequently granted traditional approval for this indication in November 2025.
In June 2021, the EC approved two new indications for use of Darzalex Faspro in combination with VCd for treatment of newly diagnosed AL amyloidosis in adult patients. The second indication was for use of Darzalex Faspro in combination with pomalidomide and dexamethasone (D-Pd) for adult patients with relapsed or refractory multiple myeloma.
In August 2021, Japan’s Ministry of Health, Labour and Welfare (MHLW) approved Darzalex Faspro in combination with VCd for newly diagnosed primary AL amyloidosis. China’s National Medical Products Administration (NMPA) approved the drug for the same indication in October 2021.
The EC approved Darzalex Faspro for adults with high-risk smouldering multiple myeloma (SMM) in July 2025. The FDA approved the drug for the same indication in November 2025.
In January 2026, the FDA granted approval to Darzalex Faspro in combination with bortezomib, lenalidomide, and dexamethasone (VRd) for adults with newly diagnosed MM who are ineligible for autologous stem cell transplant (ASCT).
This follows the previous approval granted in July 2024 for newly diagnosed MM adults who are eligible for ASCT. Darzalex Faspro is also approved in Europe for the same indications.
The drug is also approved in Canada, Switzerland, Australia and Brazil and marketed as Darzalex SC, including in Europe.
AL amyloidosis causes and symptoms
AL amyloidosis, a rare and potentially fatal blood disorder, occurs when plasma cells in the bone marrow generate abnormal antibody (immunoglobulin) proteins. In the case of AL amyloidosis, the immunoglobulin light chain gets misfolded, resulting in the formation of abnormal amyloids, which are deposited in vital organs, leading to organ damage.
Symptoms of AL amyloidosis include arrhythmia, autonomic neuropathy, chronic kidney disease, dizziness, fatigue, pain, shortness of breath, and weight loss.
Darzalex Faspro’s mechanism of action
Daratumumab is a human IgG1k monoclonal antibody (mAb) that binds to the CD38 molecule, a transmembrane glycoprotein (48 kDa) expressed on the surface of MM cells, to inhibit the proliferation of CD38-expressing tumour cells.
The drug causes rapid tumour cell death by inducing apoptosis and immune-mediated tumour cell lysis via complement-dependent cytotoxicity (CDC), antibody-dependent cell-mediated cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP).
Hyaluronan, a polysaccharide found in the extracellular matrix of the subcutaneous tissue, is depolymerised by the naturally occurring enzyme hyaluronidase to increase the permeability of the subcutaneous tissue.
Clinical trials on Darzalex Faspro
FDA approval of Darzalex Faspro was based on the results of the Phase III clinical trial, named ANDROMEDA, which compared the combination of Darzalex Faspro plus bortezomib, cyclophosphamide and dexamethasone (D-VCd) to VCd alone.
The open-label, randomised, active-controlled clinical study enrolled 388 patients with newly diagnosed AL amyloidosis and measurable haematologic disease with at least one organ affected.
The patients were randomised in a 1:1 ratio to receive treatment with either daratumumab and hyaluronidase-fihj in combination with bortezomib, cyclophosphamide, and dexamethasone (4-week cycle) or treatment with VCd alone.
The primary endpoint of the trial was the overall complete haematologic response rate, while key secondary endpoints included organ deterioration progression-free survival, event-free survival, organ response rate and overall survival, among others.
The trial met its primary endpoint, demonstrating that the patients receiving the treatment with Darzalex Faspro plus VCd achieved a haematologic complete response three times higher than patients receiving VCd alone (42% for D-VCd and 13% for VCd).
Common adverse reactions in more than 20% of the patients with AL amyloidosis who received the D-VCd combination therapy included upper respiratory tract infection, diarrhoea, peripheral oedema, constipation, peripheral sensory neuropathy, fatigue, nausea, insomnia, dyspnoea and cough.
Additional clinical trials
The FDA approval of daratumumab and hyaluronidase-fihj with VRd for newly diagnosed MM patients who were either ineligible for ASCT or who declined ASCT as primary intervention was based on the CEPHEUS (NCT03652064) open-label, randomised, active-controlled trial.
The trial randomised 395 patients across two treatment groups, Darzalex Faspro-VRd (197 patients) and VRd alone (198 patients).
Key outcome parameters assessed by an independent review committee under International Myeloma Working Group (IMWG) criteria included overall minimal residual disease (MRD) negativity and progression-free survival (PFS). The MRD negativity rate was 52.3% in the Darzalex Faspro-VRd group versus 34.8% in the VRd control group. PFS hazard ratio was 0.60 in favour of the combination regimen.
The FDA’s approval of Darzalex Faspro for high-risk SMM was based on the AQUILA (NCT03301220) open-label, randomised trial in 390 patients with high-risk SMM.
The primary efficacy endpoint was PFS assessed by an independent review committee, defined as progression to multiple myeloma under International Myeloma Working Group diagnostic criteria or death from any cause. Median PFS was not evaluable in the daratumumab and hyaluronidase-fihj arm while it was 41.5 months in the active monitoring arm. The hazard ratio was 0.49.
