Photo courtesy of Janssen
Health Canada has granted conditional approval, or a Notice of Compliance with Conditions (NOC/c), for daratumumab (Darzalex), a monoclonal antibody (mAb) targeting CD38.
The mAb is now approved to treat patients with multiple myeloma (MM) who have received at least 3 prior lines of therapy, including a proteasome inhibitor (PI) and an immunomodulatory drug (IMiD), or MM patients who are refractory to both a PI and an IMiD.
An NOC/c is authorization to market a drug with the condition that the sponsor—in this case, Janssen Inc.—undertake additional studies to verify a clinical benefit.
The NOC/c policy is designed to provide access to:
- Drugs that can treat serious, life-threatening, or severely debilitating diseases
- Drugs that can treat conditions for which no drug is currently marketed in Canada
- Drugs that provide a significant increase in efficacy or significant decrease in risk when compared to existing drugs marketed in Canada.
Studies of daratumumab
The NOC/c for daratumumab was based on a review of data from the phase 2 SIRIUS study, the phase 1/2 GEN501 study, and additional supportive studies.
The GEN501 study enrolled 102 patients with relapsed MM or relapsed MM that was refractory to 2 or more prior lines of therapy. The patients received daratumumab at a range of doses and on a number of different schedules.
The results suggested daratumumab is most effective at a dose of 16 mg/kg. At this dose, the overall response rate was 36%. Most adverse events in this study were grade 1 or 2, although serious events did occur.
The SIRIUS study enrolled 124 MM patients who had received 3 or more prior lines of therapy. They received daratumumab at different doses and on different schedules, but 106 patients received the drug at 16 mg/kg.
Twenty-nine percent of the 106 patients responded to treatment, and the median duration of response was 7 months. Thirty percent of patients experienced serious adverse events.
Findings from a combined efficacy analysis of the GEN501 and SIRIUS trials demonstrated that, after a mean follow-up of 14.8 months, the estimated median overall survival for patients who received single-agent daratumumab at 16 mg/kg was 20 months.
Five phase 3 clinical studies with daratumumab in MM patients—in relapsed and frontline settings—are ongoing. Additional studies are ongoing or planned to assess the mAb’s potential in other malignant and pre-malignant diseases in which CD38 is expressed.
Janssen has exclusive worldwide rights to the development, manufacturing, and commercialization of daratumumab for all potential indications. The company licensed daratumumab from Genmab A/S in August 2012.
