Application for Subcutaneous Daratumumab Regimen Submitted to FDA, EMA Seeking Approval in R/R Myeloma

Regulatory applications have been submitted to the FDA and European Medicines Agency (EMA) seeking approval of a subcutaneous (SC) form of daratumumab (Darzalex Faspro, daratumumab and hyaluronidase-fihj; Darzalex SC) in combination with pomalidomide and dexamethasone as treatment of patients with relapsed or refractory multiple myeloma who have received at least 1 previous therapy, Janssen Pharmaceutical announced in a press release.

The supplemental Biologics License Application submitted to the FDA, as well as the type II variation application to the EMA, are both supported by the findings from the phase 3 APOLLO clinical trial, which demonstrated improvement in the progression-free survival with the regimen compared with pomalidomide and dexamethasone (Pd) alone as treatment of patients with relapsed/refractory multiple myeloma who had been previously treated with lenalidomide (Revlimid) and a proteasome inhibitor (PI).

Subcutaneous daratumumab can be administered to the patients in quicker time, being delivered within 3 to 5 minutes, than an intravenous formulation, which usually takes several hours.

Intravenous (IV) daratumumab received its first United States approval as monotherapy for the treatment of patients with multiple myeloma in 2015 and was approved in Europe in 2016, marking this as the first anti-CD38 monoclonal antibody to be approved anywhere in the world for patients with multiple myeloma.

The IV formulation of daratumumab plus Pd was approved by the FDA in 2017 for the treatment of patients with multiple myeloma who have received at least 2 prior therapies, including lenalidomide and a PI. However, the regimen is not currently approved by the EMA for use in Europe.

"The IV formulation of Darzalex, which is approved in combination with pomalidomide and dexamethasone, is an important option for patients with multiple myeloma. We are excited to pursue the subcutaneous formulation of Darzalex for this indication as we look to reduce administration time from hours to minutes compared with the IV formulation," said Craig Tendler, MD, vice president, Late Development and Global Medical Affairs, Oncology, Janssen Research & Development, LLC, in a statement. "Today's regulatory milestones represent our continued commitment to advance innovative treatments for people living with multiple myeloma."

The subcutaneous formulation of daratumumab was approved by the FDA in 2020 as the only CD38-directed antibody approved for the treatment of patients with multiple myeloma in a subcutaneous form. As of this year, daratumumab has been approved by regulatory authorities across the globe for treatment of multiple myeloma in 6 different combination regimens and as a single agent for newly diagnosed patients to relapsed/refractory.

"Despite strong progress in multiple myeloma over the last decade, it remains a disease with significant unmet need," stated Catherine Taylor, MD, vice president, Medical Affairs Therapeutic Area Strategy, Europe, Middle East, and Africa (EMEA), Johnson & Johnson Middle East FZ-LLC. "We are pleased to pursue this important Darzalex-based combination regimen, which was in the first study showing a significant increase in progression-free survival of a subcutaneous anti-CD38 in combination with pomalidomide and dexamethasone in patients with previously treated multiple myeloma."

Full findings from the APOLLO study will be presented during an oral presentation at the upcoming 2020 American Society of Hematology (ASH) Annual Meeting.

APOLLO is a multicenter, randomized, open-label clinical trial (NCT03180736), which compared the use of daratumumab with Pd to Pd alone in patients with relapsed/refractory multiple myeloma who have previously received prior therapy with lenalidomide and a PI and progressed. The primary end point of the study is progression-free survival, and some of the secondary end points include objective response rate, very good partial response or better rate, complete response or better rate, MRD-negativity rate, time to response, duration of response, time to next therapy, overall survival, and safety.

To be eligible for the study, patients had to be at least 18 years of age and have measurable disease. Patients also had to have an ECOG performance status of 0 to 2 and a creatinine clearance of 30 mL/min or more to be included in the study. For patients who had received only 1 prior line of therapy had to have experienced disease progression by 60 days or less following a lenalidomide-based regimen. Patients who had received prior anti-CD38 therapy or pomalidomide were ineligible to enroll in the study.

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_{Janssen submits applications in the US and EU seeking approval of Darzalex Faspro (daratumumab and hyaluronidase-fihj)/Darzalex (daratumumab) subcutaneous (SC) formulation in combination with pomalidomide and dexamethasone for patients with relapsed or refractory multiple myeloma. News release. The Janssen Pharmaceutical Companies of Johnson & Johnson. November 12, 2020. Accessed November 12, 2020. https://prn.to/35n742y}