Behind the FDA Approval: Isatuximab On-Body Injector Supports ‘Patient-Centric’ Priorities in Multiple Myeloma

The FDA approved isatuximab-irfc (Sarclisa Escena) as a subcutaneous (SC) formulation for multiple myeloma on July 9, 2026, marking the first anticancer therapy cleared for delivery via an on-body injector (OBI).¹ The approval spans all previously authorized indications for intravenous (IV) isatuximab (Sarclisa). Patients can now receive the anti-CD38 monoclonal antibody through the CirCLIQ on-body delivery system or via manual SC injection, offering an alternative to an IV infusion that has historically required an hour or more to administer.

Beyond the overall trend toward SC injection, the OBI represents new opportunities to streamline administration of vital antimyeloma therapies, providing a safe method of administration that offers convenience to both myeloma care providers and patients.

“We’re trying to deliver agents more quickly, more effectively, and in a patient-centered manner,” said Joseph Mikhael, MD, MEd, in an interview with Targeted Oncology^TM.

The decision was supported by findings from the phase 3 IRAKLIA trial (NCT05405166), an open-label, noninferiority study that randomly assigned 531 patients with relapsed/refractory multiple myeloma to SC isatuximab via the on-body delivery system or IV isatuximab, both in combination with pomalidomide (Pomalyst) and dexamethasone. SC delivery met its noninferiority end point vs the IV formulation, and the OBI was associated with a lower rate of infusion-related reactions.²

To discuss the clinical and practical implications of this approval, Targeted Oncology spoke with Mikhael, a professor in the Clinical Genomics and Therapeutics Division at the Translational Genomics Research Institute, an affiliate of City of Hope Cancer Center; and a member of the American Society of Hematology’s executive committee. Mikhael, who led the first-in-human study of isatuximab, discussed how the OBI functions, what it may mean for clinic workflow and the potential for at-home administration, and how this approval fits into the broader evolution of anti-CD38 therapy in multiple myeloma.

Targeted Oncology: How have SC formulations improved the quality of treatment for patients with multiple myeloma?

Joseph Mikhael, MD, MEd: SC delivery has improved our patient care in multiple myeloma for various reasons. Our patients spend a lot of time with us in multiple myeloma in particular. Often, patients have treatments that go on for several months, if not for several years, and so being able to administer agents that take a shorter period of time, which is typical of SC when compared [with] IV formulations, has been a step forward.

Furthermore, the SC formulation allows for the lack of need for IV access. We used to use a lot of ports in multiple myeloma. We hardly ever do that anymore on an ongoing basis. It allows less needle pricks into veins, but also, the SC delivery in general results in fewer adverse events [and] fewer infusion or administration reactions.Furthermore, we can use less of the pre-medications that often take additional time and have their own [adverse events].

Using SC formulations is a more patient-centered approach that focuses on the patient experience while still delivering the same adequate, if not superior, delivery of agents—superior by the fact that often with SC formulations, there isn’t the need of mixing and matching it to weight [which] facilitates its preparation and delivery. That often can simplify the process and is less prone to error and is more likely to deliver an effective agent to a patient.

How do you feel about the FDA approval of SC isatuximab?

I’ve had the privilege of working with isatuximab since it was first developed. I actually led the first-in-human study, treated the first patient [with myeloma] with this agent in a clinical trial, and it’s very gratifying to see it now this far.

For all the years that we’ve been using it, we’ve been using it intravenously. …Although the IV infusion was generally shorter, often an hour to an hour and 15 minutes, now we can reduce that down to below 15 minutes with either a SC push or this new OBI. Again, it speaks to that evolution of cancer care as we deliver agents more quickly, more effectively, and in a patient-centered manner. I’m particularly excited to see this because I think it has been a barrier to deliver this agent because it has only been available intravenously, so now we’ll have more opportunity to deliver it through the OBI.

Can you explain how the OBI works and how it will change how isatuximab can be administered?

The technology of the OBI is fascinating. It has multiple features that make it unique compared [with] a typical SC push by a nurse, which is itself a major advance. With the OBI, the medication is prefilled in a vial and placed in the device, so there isn’t a need to mix doses…. Furthermore, this is a small device that sticks to the patient’s skin, so there isn’t an external needle that needs to be used.

When this device is applied to the skin and a button is pushed, a tiny 30-gage needle is inserted into the skin. [The needle] is not seen because it’s between the device and the skin, and it infuses the drug typically in about 12 to 13 minutes. Then when it’s done, the needle pops out and the device can be removed.

It has multiple benefits: there isn’t the careful mixing of dosing; it’s a prefilled syringe. This can be administered to the patient without necessarily nursing care. With SC injections, we require nursing care; this could potentially be administered by another individual in the clinic. It wouldn’t necessarily have to be in a traditional infusion center unit. We hardly see any kind of reaction to this in the hundreds of patients who have been treated in clinical trials. Finally, with the tiny needle, it is less arduous for the patient.

The patient’s experience is quite remarkable. In fact, in one of the clinical trials [IZALCO; NCT05704049], they evaluated giving it as a SC push vs the OBI, and the overwhelming majority of patients preferred the injector over the traditional push.³

There is the potential that with time—although it’s a bit challenging in the US—this could even be delivered at home and even self-administered by the patient. I think that will probably take us a few more steps to get there, but in the short term, being able to deliver this in the clinic and in not so traditional clinic settings will be very helpful for patients and will allow us to give this drug more quickly, more efficiently, and hopefully in a more patient-centric manner.

Do you see any challenges for physicians using the OBI routinely in their clinics?

No. In fact, I think it may even make the delivery process smoother. Typically, with the SC push, nurses are present with the patient for that whole time. Of course, we love when the nurses interact with their patients—that’s very important for multiple reasons. But here, it could be placed on the patient, and there doesn’t have to be constant supervision. It could be either done in another part of the clinic that is not the traditional infusion center, or this could be done more quickly and smoothly, because you’d be able to place this on the patient, and the nurse can then do work in other areas and come back and check on the patient later.

Every practice is different in how their flow is, but this gives that flexibility. It can be done in the traditional way—the approval from the FDA allows it to be given through a SC push as well. I think the vast majority of patients providers will go with the OBI, but I think it gives that flexibility for the community to deliver in different ways and in different settings. That will make it easier to deliver compared with giving it intravenously.

What do you see as the potential for at-home administration or self-administration using the OBI?

The potential is great. There are some self-administered and home-administered agents in oncology, but not very many. With our health care system here, it is a bit more challenging to do that, and it’s well above me to be able to adjust that. But in certain countries and certain jurisdictions where already certain medications, particularly SC ones, are being delivered at home, it has that potential, and I think that’s important for the future as we reassess how we deliver care.

Although we love to see our patients, and often we need to see our patients, many would prefer to be at home. I suspect many patients will appreciate the OBI because it’s such a simple process of applying it to the skin, letting the drug get infused, and then just taking it off. This is a very different approach than SC administration with a push. It really gives the potential for patients to do this themselves.

Even without at-home administration, the simplicity of being able to give this, the flexibility of giving it, whether it’s a community or an academic setting, inside the infusion center or in another patient room, allows us a potential that we don’t often have in oncology. I think that will make it considerably easier and preferable to administer.

What are your final thoughts on the consequences of this approval?

I would conclude by saying anti-CD38 therapy in the form of both isatuximab and daratumumab [Darzalex] are a central part of what we do in multiple myeloma. We have multiple approvals in both the frontline setting and the relapsed setting, and so these agents are here to stay. They’ve transformed the field. I always want to match the treatment to the patient, both from a biological high-risk vs standard-risk standpoint, but also on patient preference. What I would want the community to know is that we now have another way of delivering a CD38 antibody that may be particularly helpful and convenient for many of our patients, and I would be open to looking at what option is best for my patient.

Myeloma has been transformed over the last several years, and the target CD38 is particularly important. I’m fascinated by many of the combinations that are coming, not just with traditional agents, but with the novel therapies, including bispecific antibodies and others that we’re seeing combinations with CD38. I think this OBI will make a lot of that easier as we administer it with other agents that are also either given SC or IV. The fact that we can administer isatuximab so quickly and smoothly will help.

We’re moving to an era where we hope, with time, we’ll have such effective therapies that we’ll be able to treat our patients less, give them shorter periods on therapy, and give them periods of time off; but even if they do have to continue therapy, being able to deliver it in a simple manner like this will be very gratifying.

It’s easy to focus on the disease biology and the excitement of new treatments and all the novel things that are coming in myeloma. But I’m particularly happy to be focused on something that is genuinely patient-centric. This could revolutionize the patient experience with multiple myeloma, and I think this will be a particularly valuable tool in our toolbox.

REFERENCES

1. FDA approves isatuximab-irfc for subcutaneous injection for multiple myeloma indications. FDA. July 10, 2026. Accessed July 10, 2026. https://tinyurl.com/4xpwfa77

2. Ailawadhi S, Špička I, Spencer A, et al. Isatuximab subcutaneous by on-body injector versus isatuximab intravenous plus pomalidomide and dexamethasone in relapsed/refractory multiple myeloma: phase III IRAKLIA study. J Clin Oncol. 2025;43(22):2527-2537. doi:10.1200/JCO-25-00744

3. Parmar G, Capra M, Seguro F, et al. Efficacy and safety of isatuximab subcutaneous plus carfilzomib and dexamethasone in patients with relapsed/refractory multiple myeloma: results of the phase 2 study IZALCO. Blood Cancer J. 2025;16(1):16. doi:10.1038/s41408-025-01436-0