FDA Accepts sBLA for Daratumumab, Hyaluronidase-fihj for Treatment of Multiple Myeloma

A supplemental Biologics License Application (sBLA) was submitted to the FDA seeking approval for daratumumab and hyaluronidase-fihj (Darzalex Faspro; Janssen Biotech, Inc.) in combination with bortezomib, lenalidomide, and dexamethasone (D-VRd) for induction and consolidation treatment, and with lenalidomide (D-R) for maintenance treatment of adult patients with newly diagnosed multiple myeloma (NDMM) who are eligible for autologous stem cell transplant (ASCT). The submission comes after data from a phase 3 trial which met its primary goal of progression-free survival (PFS).

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Daratumumab and hyaluronidase previously received FDA approval in May 2020 for 8 indications in multiple myeloma, of which 3 are for first line therapy in newly diagnosed patients who are either eligible or ineligible for transplant. It is indicated for the treatment of adult patients with multiple myeloma in combination with D-VRd and D-R, and is the only subcutaneous CD38-directed antibody approved to treat patients with multiple myeloma.

The ongoing randomized, open-label phase 3 PERSEUS (NCT03710603) trial evaluated D-VRd induction and consolidation therapy, ASCT, and D-R maintenance therapy compared to bortezomib, lenalidomide, and dexamethasone (VRd), ASCT, and lenalidomide (R) maintenance. The median age of patients is 61 (range: 32-70) years in the D-VRd cohort and 59 (range: 31-70) years in the VRd cohort. The primary endpoint is PFS, and secondary endpoints include overall complete response (CR) or better rate, overall minimal residual disease (MRD)-negativity in patients with CR or better, and overall survival (OS).

The results demonstrated that PFS was met, and the risk of disease progression or death was reduced by approximately 58% (HR, 0.42; 95% CI 0.30-0.59; P < 0.0001). Further, treatment with D-VRd and ASCT followed by D-R maintenance had also increased the depth of response, with higher rates of CR or better stringent CR and MRD negativity compared to treatment with VRd, ASCT, and R maintenance. Approximately 64% of patients who enrolled in the maintenance phase in the D-VRd cohort were able to discontinue treatment with daratumumab and hyaluronidase after achieving a CR or better and sustained MRD-negativity after at least 2 years of D-R maintenance.

According to the authors, the safety profile of D-VRd followed by D-R maintenance was consistent with the previously established safety profiles for daratumumab and hyaluronidase, VRd, and R.

“We are committed to changing the course of multiple myeloma through building combination regimens such as D-VRd with complementary mechanisms of action. The [daratumumab and hyaluronidase]-based quadruplet therapy demonstrated a clinically significant reduction in the risk of progression or death for transplant-eligible, newly diagnosed patients with multiple myeloma,” said Craig Tendler, MD, vice president of clinical development, diagnostics, and global medical affairs at Johnson & Johnson Innovative Medicine, in a press release.

The most common adverse effects (≥20%) reported by patients with multiple myeloma who received treatment with daratumumab and hyaluronidase with combination therapy include fatigue, nausea, vomiting, diarrhea, constipation, dyspnea, insomnia, headache, pyrexia, cough, muscle spasms, back pain, hypertension, upper respiratory tract infection, peripheral sensory neuropathy, pneumonia, and peripheral edema. The most common hematology laboratory abnormalities (≥40%) were decreased leukocytes, decreased lymphocytes, decreased neutrophils, decreased platelets, and decreased hemoglobin.

“Patients are most likely to experience their deepest and most durable responses during the first line of treatment with D-VRd. This regimen has the potential to improve long-term outcomes for newly diagnosed patients and we look forward to working with the FDA on the review of this application,” said Tendler in the press release.

Reference

Johnson & Johnson. Johnson & Johnson submits supplemental Biologics License Application to U.S. FDA seeking approval of DARZALEX FASPRO® (daratumumab and hyaluronidase-fihj)-based regimen for the treatment of patients with transplant-eligible, newly diagnosed multiple myeloma. News release. January 30, 2024. Accessed January 31, 2024. https://www.investor.jnj.com/news/news-details/2024/Johnson--Johnson-submits-supplemental-Biologics-License-Application-to-U.S.-FDA-seeking-approval-of-DARZALEX-FASPRO-based-regimen-for-the-treatment-of-patients-with-transplant-eligible-newly-diagnosed-multiple-myeloma-2024-47u9-sNsTA/default.aspx