FDA Approval Expands Isatuximab Delivery Options in Multiple Myeloma

Clinical Summary:

• Design/Population: The phase 3 IRAKLIA trial randomized patients with relapsed or refractory multiple myeloma to receive subcutaneous isatuximab via an on-body injector or intravenous isatuximab, each combined with pomalidomide and dexamethasone.
• Key Outcomes: Subcutaneous isatuximab demonstrated noninferior efficacy and pharmacokinetics compared with intravenous administration, while reducing infusion-related reactions and achieving a 99.9% successful on-body injector administration rate with high patient preference.
• Clinical Relevance: These findings support subcutaneous isatuximab as a convenient alternative to intravenous administration, providing comparable efficacy and safety with an improved treatment experience for patients with relapsed or refractory multiple myeloma.

Sikander Ailawadhi, MD, Mayo Clinic, Jacksonville, Florida, discusses results from the phase 3 IRAKLIA trial comparing subcutaneous isatuximab administered via an on-body injector with the intravenous formulation in patients with relapsed or refractory multiple myeloma. 

Dr Ailawadhi reviews the study's demonstration of noninferior efficacy and pharmacokinetics with subcutaneous administration, along with favorable tolerability, high device reliability, and improved patient preference. He also discusses the FDA approval of the on-body injector formulation and its potential to simplify treatment delivery for patients receiving isatuximab-based therapy.

Transcript:

Hello, I am Sikander Ailawadhi. I'm a professor of medicine and hematology/oncology at Mayo Clinic, the Jacksonville, Florida location. I'm here today to talk to you about the IRAKLIA clinical trial in multiple myeloma.

The IRAKLIA study was a large, randomized, international clinical trial looking at the combination of isatuximab with pomalidomide and dexamethasone as the regimen, but it was comparing the intravenous version of isatuximab with pomalidomide and dexamethasone as against the subcutaneous version of isatuximab administered via an on-body injector with pomalidomide and dexamethasone. 

The patient selection included patients who had had at least 1 prior line of therapy, so patients with relapsed or refractory disease. They were assigned 1:1– half got the IV isatuximab and half got the on-body injector isatuximab, in combination with pomalidomide and dexamethasone. The primary end point was looking at the subcutaneous version through the on-body injector was noninferior to the intravenous version in its benefit to patients. An important primary coprimary end point was looking at the drug levels that were achieved in the body with the subcutaneous on-body injector version as compared to the intravenous version, making sure that the drug was absolutely appropriately absorbed, present in the body, and was able to show its benefit.

This study included 531 patients and after a median follow-up of at least 1 year, the overall response rates were kind of superimposable. The subcutaneous version did as good as the IV version. Also, the drug level was adequately achieved by the subcutaneous version. Again, the on-body injector was able to deliver adequate amount of the drug. 

There were several secondary end points looking at just how the quality of life got affected, what were some other, obviously the side effect profile, whether it was different or not. The study was also looking at the success rate of using the on-body injector, meaning did the device actually work, all of that was going to be documented. 

In all of those versions, the patient preference, quality of life, etc. was much more in favor of the subcutaneous version. The device worked almost 100% of the time, in about 99.9% of the cases, the device injections were completed without any interruptions. 

The side effect profile was also very good because the local site reactions, any skin reaction etc. happened in less than half a percent, so very safe. There were no significantly different side effects noted by the subcutaneous version of the isatuximab given via the on-body injector as compared to the intravenous version.

In conclusion, this study, the IRAKLIA study demonstrated efficacy and pharmacokinetic or drug level associated noninferiority between the isatuximab on-body injector and the intravenous version. No unexpected new or concerning side effects were observed, and there was excellent tolerability of the isatuximab on-body injector. 

The clinical benefit and safety were quite comparable, except that in fact, the on-body injector gave a smaller number of infusion reactions as compared to the intravenous version. 

All of this was reviewed very favorably, and now the on-body injector in this particular combination of isatuximab with pomalidomide and dexamethasone is currently FDA approved along with a couple other regimens where isatuximab is available for the use in multiple myeloma patients. For example, the isatuximab with bortezomib-lenalidomide-dexamethasone for newly diagnosed, and isatuximab with carfilzomib and dexamethasone also available for patients with relapse or refractory disease.

Source:

Sikander Ailawadhi, Špička I, Spencer A, et al. Isatuximab subcutaneous by on-body delivery system vs isatuximab intravenous plus pomalidomide and dexamethasone in relapsed/refractory multiple myeloma: Phase 3 IRAKLIA Study. J Clin Oncol. Published online: June 3, 2025. doi: 10.1200/jco-25-00744