On May 1, 2020, the U.S. Food and Drug Administration approved daratumumab and hyaluronidase-fihj (Darzalex Faspro™) for adult patients with newly diagnosed or relapsed or refractory multiple myeloma. The product allows for subcutaneous dosing of daratumumab.
Daratumumab and hyaluronidase-fihj was approved for the same indications as IV daratumumab:
- In combination with bortezomib, melphalan, and prednisone in newly diagnosed patients who are ineligible for autologous stem cell transplant
- In combination with lenalidomide and dexamethasone 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 one prior therapy
- In combination with bortezomib and dexamethasone in patients who have received at least one prior therapy
- As monotherapy in patients who have received at least three prior lines of therapy, including a proteasome inhibitor and an immunomodulatory agent or who are double refractory to a proteasome inhibitor and an immunomodulatory agent.
Efficacy of daratumumab and hyaluronidase-fihji (monotherapy) was evaluated in an open-label non-inferiority trial (COLUMBA; NCT03277105) randomizing 263 patients to daratumumab and hyaluronidase-fihj and 259 to IV daratumumab. The trial’s two primary endpoints were overall response rate (ORR) and pharmacokinetic endpoint of the maximum Ctrough on cycle 3, day 1 predose. Daratumumab and hyaluronidase-fihj was noninferior to IV daratumumab in both endpoints.
ORR was 41.1% for daratumumab and hyaluronidase-fihj and 37.1% for IV daratumumab with a risk ratio of 1.11 (95% CI = 0.89, 1.37). The geometric mean ratio comparing daratumumab and hyaluronidase-fihj to IV daratumumab for maximum Ctrough was 108% (90% CI = 96, 122).
Efficacy of daratumumab and hyaluronidase-fihj in combination with Velcade (Bortezomib) Melphalan-Prednisone (DVMP) was evaluated in a single-arm cohort of a multicohort, open‑label trial (PLEIADES; NCT03412565). Eligible patients were required to have newly diagnosed multiple myeloma and be ineligible for transplant. The major efficacy outcome measure, ORR, was 88.1% (95% CI = 77.8, 94.7).
Efficacy of daratumumab and hyaluronidase-fihj in combination with lenalidomide and dexamethasone (D-Rd) was evaluated in a single-arm cohort of the PLEIADES trial. Eligible patients had received at least one prior line of therapy. ORR was 90.8% (95% CI = 81.0, 96.5).
The most common adverse reaction (≥ 20%) to daratumumab and hyaluronidase-fihj monotherapy is upper respiratory tract infection. The most common adverse reactions (≥ 20%) to D-VMP are upper respiratory tract infection, constipation, nausea, fatigue, pyrexia, peripheral sensory neuropathy, diarrhea, cough, insomnia, vomiting, and back pain. The most common adverse reactions (≥ 20%) to D-Rd are fatigue, diarrhea, upper respiratory tract infection, muscle spasms, constipation, pyrexia, pneumonia, and dyspnea.
The most common hematology laboratory abnormalities (≥ 40%) to daratumumab and hyaluronidase-fihj are decreases in leukocytes, lymphocytes, neutrophils, platelets, and hemoglobin.
The recommended dose of daratumumab and hyaluronidase-fihj is 1,800 mg daratumumab and 30,000 units hyaluronidase by subcutaneous injection into the abdomen over approximately three to five minutes according to recommended schedule.
This review used the Assessment Aid, a voluntary submission from the applicant to facilitate FDA’s assessment.
Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 800-FDA-1088.
For assistance with single-patient oncology investigational new drug applications, contact OCE’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov.