Regulatory Decision Summary for Darzalex SC

Authorization was based on a randomised, open-label, active-controlled, multicentre Phase 3 study in subjects with newly diagnosed AL amyloidosis that compared the combination treatment of Darzalex SC plus cyclophosphamide, bortezomib, and dexamethasone (VCd) against VCd alone. The primary efficacy endpoint in the study was the overall hematologic response (HemCR) rate, which was the proportion of patients who achieved a complete hematologic response confirmed by a subsequent assessment during or after the study treatment. After at least 6 cycles of treatment, a higher proportion of patients in the Darzalex SC plus VCd arm were observed to have an improvement in the overall HemCR compared to those receiving VCd alone. The results demonstrated a statistically significant and clinically meaningful improvement with the addition of daratumumab to VCd in terms of the overall HemCR rate.

The safety profile for Darzalex SC combination therapy in patients with AL amyloidosis was generally consistent with the profile previously established in patients with multiple myeloma. The most common adverse events in both treatment groups were peripheral edema, diarrhea, constipation, fatigue, and nausea. Peripheral sensory neuropathy, URT infections, and cytopenias (thrombocytopenia, lymphopenia, and neutropenia) were more common in patients who received Darzalex SC. A potentially higher rate of cardiac disorder fatal adverse events was observed in Darzalex SC-treated patients early in the trial; Darzalex SC is not recommended for use in AL amyloidosis patients with pre-existing advanced cardiac disease.

Overall, the benefit/risk profile of Darzalex SC in combination with VCd for the treatment of patients with newly diagnosed AL Amyloidosis is considered to be favourable.