FDA Approves Daratumumab and Hyaluronidase-fihj for Multiple Myeloma

The FDA approved daratumumab and hyaluronidase-fihj (Darzalex Faspro) for use in adult patients with newly diagnosed or relapsed/refractory multiple myeloma.¹

The addition of this new product allows for subcutaneous dosing of daratumumab. 

“The approval of the subcutaneous formulation of daratumumab, [daratumumab and hyaluronidase-fihj], is a landmark event in the development of daratumumab,” Jan van de Winkel, PhD, chief executive officer of Genmab, the developer of daratumumab, said in a press release.² “Not only is it now the first and only subcutaneous CD38 antibody approved for the treatment of multiple myeloma, the subcutaneous administration of [daratumumab and hyaluronidase-fihj] considerably reduces treatment burden, as the fixed-dose injection is administered in approximately 3 to 5 minutes, offering patients a more convenient treatment experience.”

The efficacy of daratumumab and hyaluronidase-fihj as a monotherapy was evaluated in the open-label, non-inferiority phase III COLUMBA trial, which randomized 263 patients to daratumumab and hyaluronidase-fihj and 259 patients to intravenous daratumumab. Co-primary endpoints for the trial were overall response rate (ORR) and pharmacokinetic (PK) endpoint of the maximum Ctrough on cycle 3, day 1 pre-dose. 

The ORR was found to be 41.1% for daratumumab and hyaluronidase-fihj and 37.1% for daratumumab IV with a risk ratio of 1.11 (95% CI, 0.89-1.37). Moreover, the geometric mean ratio comparing daratumumab and hyaluronidase-fihj to daratumumab IV for maximum Ctrough was 108% (90% CI, 96-122).

Efficacy of daratumumab and hyaluronidase-fihj in combination with bortezomib (Velcade) and melphalan-prednisone (D-VMP) was also evaluated in a single-arm cohort of the multi-center, multi-cohort, open-label phase III PLEIADES trial. Patients eligible for this trial were required to have newly diagnosed multiple myeloma and were ineligible for transplant. Further, ORR was 88.1% (95% CI, 77.8-94.7).

Additionally, efficacy of daratumumab and hyaluronidase-fihj in combination with lenalidomide (Revlimid) and dexamethasone (D-Rd) was evaluated in a single-arm cohort of this trial. Eligible patients had received at least 1 prior line of therapy and the ORR was 90.8% (95% CI, 81.0-96.5).  

The most common adverse event (AE) observed in patients administered daratumumab and hyaluronidase-fihj as a monotherapy was upper respiratory tract infection. The most common AE with D-VMP were upper respiratory tract infection, constipation, nausea, fatigue, pyrexia, peripheral sensory neuropathy, diarrhea, cough, insomnia, vomiting, and back pain. The most common AE with D-Rd was fatigue, diarrhea, upper respiratory tract infection, muscle spasms, constipation, pyrexia, pneumonia, and dyspnea. 

Also, of note, the most common hematology laboratory abnormalities with daratumumab and hyaluronidase-fihj were decreased leukocytes, decreased lymphocytes, decreased neutrophils, decreased platelets, and decreased hemoglobin.

The FDA recommended a dose of 1,800 mg of daratumumab and 30,000 units of hyaluronidase administered subcutaneously into the abdomen over approximately 3 to 5 minutes, per the recommended dosing schedule.

“As seen in the pivotal study supporting the approval, this reduction in infusion time from hours to minutes led to higher satisfaction levels for patients and in addition, infusion-related reactions were both mild and significantly reduced with this formulation of daratumumab,” van de Winkel continued. “We are very much looking forward to the launch of [daratumumab and hyaluronidase-fihj] in the US and the potential for positive impact it will have on the lives of the patients receiving the drug.”

The combination of daratumumab and hyaluronidase-fihj is now approved for the following indications, of which intravenous daratumumab had already received:

• In combination with bortezomib (Velcade), melphalan (Evomela), and prednisone (Rayos) (VMP) in newly diagnosed patients who are ineligible for autologous stem cell transplant

• In combination with lenalidomide (Revlimid) and dexamethasone (Ozurdex) (Rd) in newly diagnosed patients who are ineligible for autologous stem cell transplant and in patients with relapsed or refractory multiple myeloma who have received at least 1 prior therapy

• In combination with bortezomib and dexamethasone in patients who have received at least 1 prior therapy

• As a monotherapy in patients who have received at least 3 prior lines of therapy, including a proteasome inhibitor and an immunomodulatory agent or who are double refractory to a PI and an immunomodulatory agent

References:

1. FDA. FDA approves daratumumab and hyaluronidase-fihj for multiple myeloma. FDA website. Published May 1, 2020. fda.gov/drugs/drug-approvals-and-databases/fda-approves-daratumumab-and-hyaluronidase-fihj-multiple-myeloma. Accessed May 1, 2020. 

2. Genmab Announces U.S. FDA Approval of Subcutaneous Formulation of Daratumumab, DARZALEX FASPRO™ (daratumumab and hyaluronidase-fihj), for the Treatment of Patients with Multiple Myeloma [news release]. Copenhagen, Denmark. Published May 1, 2020. globenewswire.com/news-release/2020/05/01/2026290/0/en/Genmab-Announces-U-S-FDA-Approval-of-Subcutaneous-Formulation-of-Daratumumab-DARZALEX-FASPRO-daratumumab-and-hyaluronidase-fihj-for-the-Treatment-of-Patients-with-Multiple-Myeloma.html. Accessed May 1, 2020.