Regulatory Decision Summary for Darzalex SC

Darzalex (an intravenous formulation of daratumumab), alone or in combination with chemotherapy, is authorised in Canada for the treatment of multiple myeloma. The current submission provides data to support a new subcutaneous (SC) formulation of daratumumab, namely, Darzalex SC, for the authorised multiple myeloma indications. Authorization is supported by two studies.

The first study was a comparative study of Darzalex SC and Darzalex in patients with relapsed/refractory multiple myeloma. The study demonstrated that the exposure to daratumumab resulting from Darzalex SC is not unacceptably less than that achieved with the standard daratumumab intravenous (IV) dose from Darzalex. In addition, based on an efficacy endpoint of Overall Response Rate (ORR), evidence of non-inferiority of Darzalex SC compared to Darzalex was also demonstrated.

In terms of risk, the overall proportion of patients having adverse events was similar between treatment arms; however, a notably higher incidence of neutropenia was observed in patients administered Darzalex SC. The increased neutropenia associated with Darzalex SC was not considered to be clinically meaningful as there were no significant increases in febrile neutropenia on the Darzalex SC arm. Furthermore, the incidence of infections and infestations were also comparable between the Darzalex SC and Darzalex arms. Injection site reactions (ISRs) were identified as new adverse events associated with Darzalex SC and mainly resulted in erythema and rash. Lastly, in some patients weighing >120 kg, lower daratumumab exposures was observed following Darzalex SC administration. The impact of such decreased exposures on efficacy was unclear due to limited number of patients weighing >120 kg who were studied. Additionally, the variability in exposures and responses were observed across body weights as well as in patients who received Darzalex. The risk information has been labelled in a Darzalex SC-specific Product Monograph (PM).

The second study was a single arm study evaluating the safety of Darzalex SC when administered with standard multiple myeloma treatment regimens, and no new safety concerns were identified.

The exposure to daratumumab resulting from Darzalex SC is not less than that achieved with the standard daratumumab IV dose. The level of efficacy as well as the safety profile of Darzalex SC is therefore not expected to be appreciably different to that of Darzalex. Accordingly, Darzalex SC is considered to have a benefit-risk profile that is comparable to that of the currently authorized Darzalex for the authorised multiple myeloma indications. A Notice of Compliance has been granted.