Xavier Leleu, MD, PhD, head of the department of hematology and myeloma clinic at Hôpital La Mileterie in Poitiers, France, sat down with Pharmacy Times® at the 22nd annual International Myeloma Society (IMS) meeting and exposition in Toronto, Canada, to discuss findings from the IRAKLIA and ISASOCUT studies evaluating the on-body injector (OBI) for subcutaneous administration of isatuximab (Sarclisa).
Leleu shared that IRAKLIA demonstrated non-inferior efficacy and safety compared with IV delivery, with consistent pharmacokinetics across weight groups. He also noted that ISASOCUT and ISALCO further supported OBI use, showing comparable outcomes to standard regimens and clear advantages over manual push, offering patients a more convenient and reliable treatment option.
Pharmacy Times: Can you start by introducing yourself?
Xavier Leleu, MD, PhD: I’m Professor Xavier Leleu. I’m head of department in a city called Poitiers in France, and I’m a member of the IFM and an expert in myeloma.
Pharmacy Times: Can you summarize the key findings from the IRAKLIA and ISASOCUT studies on the on-body injector (OBI) for Sarclisa?
Leleu: The CD38 monoclonal antibody named isatuximab (Sarclisa) up to now was administered IV. We have improved the IV administration by shortening it to 30 minutes, which really makes it very convenient for the outpatient clinic.
Now, we still have this IV approach, but you need to find a vein. Some patients do not have easy access to veins, so it needed improvement. We know from daratumumab that it was possible to switch from IV to subcutaneous manual push. But with solid monoclonal antibodies, there are things you need to be careful with. Number one, it’s thicker than a regular product. Number two, it is a greater volume.
The company Sanofi wanted to develop their isatuximab Sarclisa on a subcutaneous formulation route but thought that it could be very interesting to use a completely new technology: a device called an on-body injector, or on-body delivery system. It is a small, rounded, automated box. The needle is very thin, no more than 30 gauge. The needle is hidden from the patient, and it retracts at the end of the injection. It’s convenient, safe, and easy and greatly improves the quality of life for patients who receive many injections.
To demonstrate that isatuximab could be given as a flat dose of 1400 mg with the OBI, Sanofi had to run a registrational study, as well as a non-inferiority study to compare IV isatuximab with this new subcutaneous OBI route.
At our school, at EHA 2025 here at IMS in Toronto, there was a presentation of the IRAKLIA data. IRAKLIA is a non-inferiority phase 3 study that met its two co-primary endpoints. One was activity (the VGPR and greater rate), and the second was pharmacokinetics, measured by the C-trough after a couple of cycles. The VGPR was studied at 8 months, and the C-trough was studied prior to cycle 6, day 1. Both endpoints were met, showing non-inferiority: subcutaneous OBI was equivalent to IV.
Interestingly, with the pharmacokinetics, the OBI subcutaneous route actually had greater levels than IV. So, it was still non-inferior, but with greater levels than IV. This is very important because when you use a flat dose, you have to consider that the same 1400 mg dose (10 mL in the device) is given to patients who may weigh 40 kg or more than 80 kg. You need to make sure serum concentrations are in range across these patients.
For lighter patients (~40 kg), levels are higher, but activity and safety profiles remained the same. For heavier patients (80+ or 100+ kg), levels were still in the normal range, with the same activity and safety profile. IRAKLIA was able to demonstrate this across subgroups, showing consistent activity, serum concentrations, and safety.
That was IRAKLIA. There are other important studies alongside it. IRAKLIA was the registrational study, but it only looked at IV versus subcutaneous in the regimen of isatuximab, pomalidomide, and dexamethasone. For patients to use subcutaneous OBI isatuximab flat dose across all regimens where isatuximab is approved, several phase 2 studies were needed.
One of them, called ISASOCUT, was run in France and will be presented tomorrow morning in Toronto. It demonstrated that isatuximab in combination with bortezomib is probably the most important regimen containing isatuximab. In newly diagnosed myeloma, the ISA-VRD regimen with subcutaneous OBI isatuximab flat dose showed results superimposable to those published in Nature Medicine last year and in The New England Journal of Medicine last year. This is very reassuring, as it means we can use isatuximab across the frontline regimens that have transformed survival for patients.
There is also a third study that is absolutely key for your audience: ISALCO. ISALCO is extremely interesting because Sanofi asked themselves, if they developed subcutaneous manual-push isatuximab, why also go with the device? Is the device so much better than the manual push? ISALCO demonstrated that the OBI device is indeed much better than the manual push.
So, it’s not just a switch from IV to subcutaneous—it’s really IV to the best possible subcutaneous option, with OBI being superior to manual push.