At EHA 2025 in Milan I am presenting the IRAKLIA study on behalf of all the co-authors and Sanofi pharmaceutical company. It’s a phase III randomised non-inferiority study to demonstrate that the isatuximab subcutaneous formulation with a little device we call an on-body delivery system, or on-body injector, is non-inferior to the IV formulation. So in the future, hopefully, it will be available for us worldwide.

What is the study design?

The study design was a non-inferiority study, phase III, as I’ve said, randomised 1:1 in patients in the relapsed setting using an isatuximab, pomalidomide, dexamethasone regimen but in one arm isatuximab was IV, in the other arm isatuximab was subcutaneous but not manual touch, using this on-body delivery system. There were two coprimary endpoints, two primary endpoints – overall response rate and C trough, the serum concentration, pre-cycle 6. There were a number of key secondary endpoints including VGPR rate, C trough, serum concentration, residual serum concentration, much earlier – cycle 2. There were also quality of life questionnaires and other key secondary endpoints. So the study has one year of follow-up and had read for the primary endpoint.

What were the results of this study?

Two primary endpoints, the overall response rate we demonstrated that the overall response rate was very similar across the two arms and so the study is positive for the response rate. It met the non-inferiority criteria and the 95% confidence interval lower boundary was above the non-inferiority lower margin that was qualifying the study as non-inferior, so positive. So that’s for response rate, the first of the two primary endpoints.

The second primary endpoint was the residual serum concentration, C trough, right before cycle 6, steady state per request of the FDA, Food and Drug Administration. Again, it was non-inferior, about equivalent, across subQ [??] and IV. It was actually superior in the subQ but anyway it met non-inferiority. So that was the primary endpoints, the two primary endpoints, that were the endpoints that would immediately decide whether the study was positive and because it’s a registrational study then Sanofi could register, get an approval [??] after or whether the study was negative and the study is largely positive.

What is the clinical significance of these results?

The clinical significance is absolutely major, it’s absolutely groundbreaking for various reasons. Number one, right now we have two CD38 monoclonal antibodies, we have the historic one, daratumumab, and we have the isatuximab. It’s important to have various options for patients and their families. The thing with daratumumab is it’s available as a manual push subcutaneous formulation. The isatuximab is IV and even with the fast IV, 30 minute, option, still it’s not what the patient wants. What the patient wants is something that could not be IV in the vast majority of the time.

So here we’re going to have a subQ formulation of isatuximab and so the two CD38 monoclonal antibodies, daratumumab and isatuximab, will be subcutaneous and that’s really lovely. That’s point number one. Point number two, which is the most important aspect of the study, is that… I have grey hair so I personally have lots of experience in myeloma and I’ve seen a lot of drugs initially developed IV becoming subcutaneous available, which is lovely and great. But I never thought that we could imagine, rethink, the complete concept of subcutaneous formulation and here is this device where you plug your vial, you stick it to your skin, it’s on tightly, automated, it’s individually [??] to the thickness of your skin. The needle is retracted, gets out, gets in, it’s really painless. This way of totally rethinking the subcutaneous formulation with the device is really gigantically smart, it’s so genius. That is really what I love in the technology is that we were used to manual push and we would have thought that isatuximab would be manual push but actually it’s not. There’s a new device, a new way of giving it, much less harmful, much simpler, automated, which is going to simplify the life of the patients, simplify the life of the nurse, simplify the delivering of the drug. So the fact that the smart people can imagine something totally groundbreaking and genius is really always very interesting.

So this device, I think, is here to stay. This device, I think it’s probably going to be the way for all the subQ products to be administered in the future because the patients in a different study got [??] – they said that the device was much, much, much better than the manual push, less pain, less local reaction, much easier to use, much more patient friendly. So these are the two main aspects of what the study is about.

Is there anything else you would like to add?

I’m fortunate because I was invited to give the talk and share these incredible developments. I’m happy because the technology comes to medicine and helps the medicine and this is always amazing to see how people, very smart, can think about improving things constantly and this is really great. I think it’s also great for the patient, for the families, for all the team worldwide because the CD38 monoclonal antibodies are very important drugs for myeloma, they have transformed the myeloma survival of the patients. So we use a lot of them and so to improve the way we give that drug to the patients is always very important because it concerns 100% of the patients worldwide. So I do think that this IRAKLIA study is really incredible in that it brings something amazing to the patients for the future and this is really lovely.