FAQ: Insights on On-Body Injector for Anti-CD38 in Multiple Myeloma

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) issued an opinion recommending the approval of subcutaneous (SC) administration of isatuximab (Sarclisa).¹ Although it is not the first subcutaneous therapy in multiple myeloma, the use of an on-body injector (OBI) in the supporting phase 3 IRAKLIA trial (NCT05405166) gives the topic of subcutaneous administration even greater promise to improve patient convenience.

This advancing field could lead to at-home administration, whether by a visiting nurse or even being given by the patient or a caregiver.

This FAQ explores the clinical results, patient benefits, and future potential of this technology with supporting commentary from an in-depth interview with Sikander Ailawadhi, MD, who treated patients in the IRAKLIA trial and leads the myeloma group at the Mayo Clinic in Jacksonville, Florida.

1. What is the background for using subcutaneous injections to treat multiple myeloma?

Historically, myeloma treatments were primarily intravenous (IV) or oral. However, the field has increasingly shifted toward SC administration to address the logistical burdens of IV therapy, such as long infusion times and frequent travel to healthcare facilities. SC formulations of drugs like bortezomib (Velcade) and daratumumab (Darzalex) have set a precedent for this transition.

"Going forward, the focus is in getting as many more drugs available subcutaneous, because [of] patient convenience, time of treatment, time away from family, time away from work, and all those considerations,” said Ailawadhi.

2. What is an OBI and how does it work?

An OBI is a wearable, hands-free device designed to deliver high-volume medications subcutaneously through automated technology. The specific device used in the IRAKLIA study was the enFuse system. It utilizes a hidden and retractable 30-gauge needle that is significantly thinner than the needles typically used for manual SC injections, which helps to reduce patient pain and anxiety.¹

Because the OBI provides automated, constant delivery pressure, it eliminates the physical burden on nurses who would otherwise have to perform a manual ‘push’ with a syringe, and it allows patients the freedom of movement to perform light, nonstrenuous activities during the administration.

"While we use a lot of subcutaneous agents, this on-body injector is a very unique addition to how drugs are given in myeloma. This is the first time that an immunotherapy, a targeted monoclonal antibody, is being administered in the form of an on-body injector,” said Ailawadhi.

3. What were the results of the IRAKLIA phase 3 trial?

The IRAKLIA trial successfully demonstrated that SC isatuximab administered via an OBI was noninferior to the standard IV version in terms of both efficacy and drug concentration levels in the blood. The objective response rate (ORR) was nearly identical between the 2 groups, and the safety profile remained consistent, with no new safety concerns identified.²

"The key takeaways were that the trial met its primary end point... the SQ isatuximab through OBI with pom-dex [pomalidomide (Pomalyst) plus dexamethasone] was not inferior to the IV isatuximab with pom-dex, and in fact, the outcomes—both the efficacy, which is the clinical benefit, and the safety—were kind of similar. The SQ isatuximab with OBI gave exactly the same outcomes as the IV version, and there were no new safety signals or concerns noted,” said Ailawadhi.

4. What was the European Medicines Agency’s CHMP decision regarding the OBI?

On March 27, 2026, the CHMP issued a positive opinion recommending the approval of SC isatuximab via OBI or manual injection.¹ This recommendation covers all currently approved indications for the IV formulation in the EU. The decision was heavily influenced by the trial’s high success rate in drug delivery and high levels of patient and staff satisfaction.

"The EMA has looked at this very favorably, because of the clinical trial results, the safety, the benefit, how…it showed patient satisfaction being very good, staff satisfaction being very good…. This device is so effective…it had more than a 99% success rate in delivering the drug," said Ailawadhi.

5. How do patients feel about using the OBI vs IV administration?

Clinical data and patient questionnaires showed that those using the OBI reported significantly higher satisfaction compared with those receiving IV infusions. Patients appreciated the freedom of movement allowed by the wearable device and the reduced discomfort associated with the injection process.

Beyond IRAKLIA, the IZALCO phase 2 study (NCT05704049) played a critical role by allowing patients to experience both IV and SC administration and then switch.³ This ‘crossover’ design provided direct evidence of patient preference.

“The patients were then given the option of, ‘are you going to want to stay with the IV or the SC?’ Each patient was, in a way, controlled for themselves, and overwhelmingly, the patients were more in favor of the SC version,” Ailawadhi noted.

6. How can this technology benefit healthcare professionals?

The OBI helps optimize clinical workflows by reducing the time patients spend in infusion chairs. This freed-up capacity allows hospitals to treat more patients without increasing physical space. Furthermore, nursing staff benefit from a reduced physical burden compared with manual SC injections, which require constant pressure over several minutes.

"We have a finite amount of resources at our disposal... If there is a subset of patients that can be treated, potentially at home…that frees up the space to accommodate other patients that may unfortunately have to wait, because now we have to schedule them on time, and there are limited chairs and limited spaces available,” commented Ailawadhi.

7. Could this lead to self-administration at home for patients with myeloma?

Although current studies generally require healthcare professionals administering the drug, the success of the OBI opens the door for future self-administration. This could drastically reduce “time toxicity” of the hours patients lose to travel and clinic visits and help bridge healthcare disparity gaps for those living in rural areas.

"Just imagine if those patients can get this drug either delivered to them, or can collect and bring it home,” said Ailawadhi. “Once it is put on the OBI, they can stick it on, inject it themselves, and now suddenly a drug which is a game changer…can now be administered to wider reach of patients, rather than those who have the means and ability to come into a treating office.”

9. What is the current regulatory outlook for the OBI in the United States?

In the US, the isatuximab SC formulation and the OBI are currently under review by the FDA, with a recent extension of the target date to July 23. Ailawadhi is hopeful for an initial approval for clinical use, but because only a small number of patients in Europe were treated at home, the data would likely only support the OBI in the clinic for the time being.

" As the FDA is reviewing this, they may end up approving it, but I don't think they will yet approve self-administration,” said Ailawadhi. “The home administration was done only in a handful of patients, and all of that was done outside the US. I think they will probably ask for more data, especially in the US...”

10. What is the broader outlook for self-administration of myeloma therapies in the US?

In Europe, the SC formulation of daratumumab, another anti-CD38 antibody, recently received a label update that allowed patients or caregivers to give the injection from the fifth dose and beyond, provided their physician deems it appropriate and they receive training.⁴ However, this approach is not yet favored in the US.

“That is where the field could head... But I don't think we're ready for it yet. I don't think the data [are] ready for that,” said Ailawadhi.

REFERENCES

1. Sanofi’s Sarclisa subcutaneous formulation administered via on-body injector recommended for EU approval by the CHMP to treat multiple myeloma. Sanofi. March 27, 2026. Accessed April 10, 2026. https://tinyurl.com/bdkhpkd3

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 (SC) plus carfilzomib and dexamethasone (Isa-Kd) in patients with relapsed/refractory multiple myeloma (RRMM): Results of the phase 2 study IZALCO. J Clin Oncol. 2025;43(suppl 16):7526. doi:10.1200/JCO.2025.43.16_suppl.7526

4. Johnson & Johnson’s DARZALEX® (daratumumab) becomes the first oncology injectable approved for administration by patients or caregivers. Johnson & Johnson. March 27, 2026. Accessed April 10, 2026. https://tinyurl.com/muakmecu