FDA, EMA Receive Applications for Subcutaneous Daratumumab in Myeloma

The applications for subcutaneous daratumumab in smoldering multiple myeloma are supported by data from the ongoing phase 3 AQUILA study (NCT03301220). Initial findings from the AQUILA trial are expected to be presented at the 2024 American Society of Hematology Annual Meeting & Exposition (ASH).

Developers Johnson & Johnson have submitted regulatory applications to the FDA and the European Medicines Agency (EMA) seeking approval of daratumumab and hyaluronidase-fihj (Darzalex Faspro) for adults with high-risk smoldering multiple myeloma, according to a press release.¹

In the case of smoldering multiple myeloma, a precursor of active disease, abnormal cells are detectable in the bone marrow, although this condition is typically asymptomatic among patients. According to the press release, the standard strategy for managing smoldering multiple myeloma involves observing a patient to track their disease before initiating therapy around the time of biochemical progression and/or end-organ damage.

Developers designed daratumumab and hyaluronidase-fihj as a subcutaneous formulation of the CD38-targeting antibody to treat those with multiple myeloma. The agent is co-formulated with the drug delivery technology recombinant human hyaluronidase PH20 (rHuPH20).

“There remains an unmet need for early interventions and treatments that are both effective and well tolerated in [patients] living with smoldering multiple myeloma at high-risk of progressing to active multiple myeloma,” Yusri Elsayed, MD, MHSc, PhD, global therapeutic area head of Oncology and Innovative Medicine at Johnson & Johnson, stated in the press release.¹ “[Daratumumab] has changed the standard of care in multiple myeloma, and with these submissions to the FDA and EMA, this therapy could become the first approved treatment for patients with high-risk smoldering multiple myeloma, potentially shifting the treatment paradigm.”

The applications for subcutaneous daratumumab in smoldering multiple myeloma are supported by data from the ongoing phase 3 AQUILA study (NCT03301220). Initial findings from the AQUILA trial are expected to be presented at the 2024 American Society of Hematology Annual Meeting & Exposition (ASH).

Investigators of the multi-center, randomized phase 3 AQUILA trial are assessing treatment with subcutaneous daratumumab vs active surveillance among 390 patients with high-risk smoldering multiple myeloma. In the experimental arm, patients will receive subcutaneous daratumumab at 1800 mg plus rHuPH20 at 2000 U/mL once weekly in cycles 1 and 2 followed by every 2 weeks for cycles 3 to 6 and then every 4 weeks thereafter.² Those assigned to the comparator arm will not receive any study therapy but will undergo the same disease evaluations at a similar frequency as patients assigned to the daratumumab arm.

The trial’s primary end point is progression-free survival (PFS) per International Myeloma Working Group (IMWG) criteria. Secondary end points include time to biochemical or diagnostic progression, overall response rate, complete response rate, duration of response, time to response, time to frontline treatment for multiple myeloma, PFS on first-line treatment, overall survival, safety, pharmacokinetics, and quality of life.

Patients 18 years and older with a diagnosis of high-risk smoldering multiple myeloma per IMWG guidelines, clonal bone marrow plasma cells of 10% or higher, and an ECOG performance status of 0 or 1 are eligible for enrollment on the trial. Additionally, patients of childbearing potential must have a negative serum or urine pregnancy test result within 2 weeks before treatment randomization to be eligible for enrollment on the trial.

Those with primary systemic amyloid light-chain amyloidosis or exposure to prior daratumumab or anti-CD38 antibodies, approved or investigational therapies for smoldering multiple myeloma or multiple myeloma, or investigational agents or invasive investigational medical device for any indication within 4 weeks or 5 half-lives of randomization are ineligible for enrollment on the trial. Having a medical or psychiatric condition or disease such as active systemic disease that may interfere with study procedures is also grounds for exclusion from enrollment.

References

1. Johnson & Johnson submits applications in the U.S. and EU seeking approval of DARZALEX FASPRO® / DARZALEX® as subcutaneous monotherapy for high-risk smoldering multiple myeloma. News release. Johnson & Johnson. November 8, 2024. Accessed November 8, 2024. https://tinyurl.com/4wkve363
2. A study of subcutaneous daratumumab versus active monitoring in participants with high-risk smoldering multiple myeloma. ClinicalTrials.gov. Updated October 26, 2024. Accessed November 8, 2024. https://tinyurl.com/4fa722fj