Janssen Seeks Final FDA Approval for Darzalex Combo Therapy for Newly Diagnosed Multiple Myeloma

Janssen has is seeking approval from the U.S. Food and Drug Administration (FDA) for Darzalex (daratumumab) — in combination with standard Revlimid (lenalidomide) and dexamethasone — as a treatment for newly diagnosed multiple myeloma patients ineligible for a stem cell transplant.

Janssen’s supplemental Biologics License Application (sBLA) is based on data from the MAIA Phase 3 trial (NCT02252172), where the triple combination reduced the risk of disease progression or death by 45% compared with standard care alone, and doubled the number of patients who had a complete response to treatment.

The first part of the submission package was submitted in January, and the final part is now complete.

“We are pleased to complete the latest Darzalex submission based upon the Phase 3 MAIA study,” Yusri Elsayed, MD, PhD, and a vice president at Janssen Research & Development, said in a press release.

The open-label, multicenter MAIA study included 737 untreated patients (with a median age of 73 years) who were ineligible for high-dose chemotherapy and stem cell transplants.

Participants were randomized to the triple therapy or the standard treatment (Revlimid with dexamethasone) in four-week cycles. Darzalex was given by intravenous infusion weekly in cycles 1 and 2, every two weeks in cycles 3 to 6, and every four weeks from cycle 7. Celgene’s Revlimid was given on days 1–21 of each cycle, while 40 mg dexamethasone, a corticosteroid, was given once a week.

After a median follow-up of 28 months, the triple therapy lowered the risk of disease progression or death by 45% compared with standard treatment. The median progression-free survival — the length of time during or after treatment without worsening symptoms — was 31.9 months with standard treatment, but had not been reached in the group also given Darzalex, which means that those patients were still responding to the medication.

Also, adding Darzalex led to superior rates of complete responses or the disappearance of all cancer signs (48% versus 25% for standard treatment), very good or better partial responses (79.3% versus 53.1%), and overall responses (93% versus 81%).

The most common serious or life-threatening side effects for Darzalex with Revlimid and dexamethasone were low levels of neutrophils and white blood cells, pneumonia, and anemia. Infusion-related reactions occurred in 41% of patients, 3% being severe or life-threatening.

The findings from this Phase 3 study were presented at the 2018 American Society of Hematology (ASH) Annual Meeting in December 2018.

Discovered by Genmab, Darzalex is an antibody that targets a surface protein called CD38, which is found in high numbers in multiple myeloma cells. Darzalex is designed to bind to CD38 to block tumor cell growth and cause myeloma cell death. The therapy is approved for other multiple myeloma indications, including as a combination therapy with Revlimid and dexamethasone for people who have received at least one prior treatment.

Janssen’s application is being reviewed under the FDA’s Real-Time Oncology Review pilot program, which is intended to explore a more efficient review process to make new treatments available to patients as soon as possible.