Isatuximab Combo Earns FDA Priority Review in Transplant-Ineligible NDMM

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The FDA has set a Prescription Drug User Fee Act Date of September 27, 2024, for the isatuximab combination in transplant-ineligible NDMM.

Supporting data for the sBLA and the regulatory submission in the European Union came from the phase 3 IMROZ trial (NCT03319667).

Supporting data for the sBLA and the regulatory submission in the European Union came from the phase 3 IMROZ trial (NCT03319667).

The FDA has granted priority review to a supplemental biologics license application (sBLA) for isatuximab (Sarclisa) plus bortezomib (Velcade), lenalidomide (Revlimid), and dexamethasone (VRd) as a treatment for those with transplant-ineligible newly diagnosed multiple myeloma (NDMM), according to a press release from the developers, Sanofi.1

The regulatory agency has set a Prescription Drug User Fee Act date of September 27, 2024, for its decision on approving the isatuximab-based regimen in this patient population. Additionally, a regulatory submission for the same indication is currently under assessment in the European Union.

“Despite recent advancements in multiple myeloma treatment, there remains a significant unmet need for new frontline therapies, particularly for patients who are transplant-ineligible who can [have] poor outcomes from the disease,” Dietmar Berger, MD, PhD, chief medical officer and global head of Development at Sanofi, said in the press release.1 “The filing acceptances, as well as the FDA’s priority review designation, reinforce our confidence in [isatuximab] as a potential best-in-class treatment and represent a critical step toward advancing this combination in difficult-to-treat cancer.”

Supporting data for the sBLA and the regulatory submission in the European Union came from the phase 3 IMROZ trial (NCT03319667). According to findings from the trial’s planned interim analysis that investigators highlighted in December 2023, combining isatuximab with VRd produced a statistically significant progression-free survival (PFS) improvement compared with VRd alone, which met the trial’s primary end point.2

The safety and tolerability of the experimental combination in this trial were comparable with prior reports of each individual agent.

“The IMROZ trial outcome is promising for patients with newly diagnosed multiple myeloma who are transplant-ineligible, as there remains a significant unmet need for potential new therapies,” principal study investigator Thierry Facon, MD, professor of Hematology in the Department of Hematology at Lille University Hospital, Lille, France, and a member of French Academy of Medicine, said in a press release on these findings.2 “First-line therapeutic options are critical for all patients, but especially for those who are transplant-ineligible, given attrition rates in subsequent lines of therapy.”

Investigators will present updated findings from the IMROZ study at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting and the 2024 European Hematology Association Congress (EHA).

In the multi-center, international IMROZ study, 446 patients with transplant-ineligible NDMM were assigned to receive VRd alone or in combination with isatuximab. Investigators administered isatuximab intravenously at 10 mg/kg once weekly for 5 weeks during the first 42-day cycle followed by once every 2 weeks in cycles 2 to 4 plus bortezomib subcutaneously, lenalidomide orally, and dexamethasone intravenously or orally. Patients then received isatuximab every 2 weeks from cycles 5 to 17 followed by every 4 weeks in cycle 18 and onward as part of 28-day schedules plus lenalidomide and dexamethasone until progressive disease or unacceptable toxicity.

The trial’s primary end point was PFS. Secondary end points included complete response rate, minimal residual disease negativity, very good partial response or better rate, overall survival, overall response rate, time to progression, duration of response, time to first response, and time to best response.

Patients 18 to 80 years old with newly diagnosed multiple myeloma not eligible for transplant were eligible for enrollment on the trial.3 Having evidence of measurable disease was another requirement for enrollment.

Those who had prior therapy for multiple myeloma or an ECOG performance status of more than 2 were ineligible for study entry. Patients were also unsuitable for enrollment if they had inadequate organ function or any other prior or ongoing health conditions that were incompatible with the study’s design.

References

  1. Press release: Sarclisa accepted for FDA priority review for the treatment of transplant-ineligible newly diagnosed multiple myeloma. News release. Sanofi. May 27, 2024. Accessed May 28, 2024. https://tinyurl.com/5xa545er
  2. Press release: Sarclisa® (isatuximab) Phase 3 trial met primary endpoint of progression free survival in patients with newly diagnosed multiple myeloma not eligible for transplant. News release. Sanofi. December 7, 2023. Accessed May 28, 2024. https://tinyurl.com/4bpz6zdv
  3. Clinical benefit of SAR650984, bortezomib, lenalidomide and dexamethasone combination in NDMM patients not eligible for transplant (IMROZ). ClinicalTrials.gov. Accessed May 28, 2024. https://tinyurl.com/52jbpx4u
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