| 📌 The essentials On April 22, 2026, Sanofi announced that the FDA extended by up to three months the target action date for its review of Sarclisa subcutaneous (SC), a new formulation of isatuximab-irfc (Sarclisa) designed to replace IV infusion with an on-body injector (OBI). The revised PDUFA date is July 23, 2026. The extension is a delay, not a rejection. The clinical basis: The Phase 3 IRAKLIA trial (NCT05405166), published in the Journal of Clinical Oncology, demonstrated non-inferiority of Sarclisa SC versus Sarclisa IV across all co-primary and key secondary endpoints, including a striking reduction in infusion-related reactions from 25% (IV) to 1.5% (SC). EU status: The EMA’s CHMP issued a positive opinion recommending approval of Sarclisa SC on March 26, 2026. If the FDA approves, Sarclisa SC would become the first anticancer treatment ever administered through an on-body injector. |
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Multiple myeloma is the second most common blood cancer. It is not curable for most patients, which means that the drugs used to treat it and the manner in which they are delivered become part of a patient’s life for the long term. Infusion-based regimens, administered intravenously in a clinical setting, require patients to spend hours in infusion chairs, sometimes repeatedly across months or years of treatment. For a drug like Sarclisa (isatuximab-irfc), which is given weekly during the first treatment cycle and biweekly thereafter, that burden is substantial and ongoing.
On April 22, 2026, Sanofi announced that the FDA has extended by up to three months the target action date for its review of Sarclisa subcutaneous (SC), a new formulation designed to replace the IV infusion with an on-body injector, or OBI. The revised PDUFA date is July 23, 2026. The extension is a delay, not a rejection. The clinical evidence package behind it, built on the Phase 3 IRAKLIA trial, is solid, and the European Medicines Agency’s CHMP has already issued a positive opinion recommending approval. If the FDA ultimately approves Sarclisa SC, it would become the first anticancer treatment ever administered through an on-body injector.
This post covers what Sarclisa is and why it matters in the myeloma treatment landscape, what the OBI is and how it works, what IRAKLIA showed, what the FDA extension means in practice, and where EU and U.S. regulatory timelines stand.
What Is Sarclisa and What Is It Already Approved For?
Sarclisa (isatuximab-irfc) is an anti-CD38 monoclonal antibody. CD38 is a surface protein that is highly and uniformly expressed on the surface of multiple myeloma cells, making it a well-validated therapeutic target. By binding to a specific epitope on the CD38 receptor, Sarclisa triggers multiple antitumor mechanisms: direct induction of programmed cell death (apoptosis), antibody-dependent cellular cytotoxicity, and complement-dependent cytotoxicity. It also modulates immune cells in the tumor microenvironment.
In the U.S., Sarclisa is currently approved in its intravenous formulation across three indications:
| Indication | Combination partner(s) | Approval year |
|---|---|---|
| Relapsed/refractory MM, 2 or more prior lines including lenalidomide and a proteasome inhibitor | Pomalidomide + dexamethasone (Isa-Pd) | 2020 |
| Relapsed/refractory MM, 1 to 3 prior lines | Carfilzomib + dexamethasone (Isa-Kd) | 2021 |
| Newly diagnosed MM, transplant-ineligible | Bortezomib + lenalidomide + dexamethasone (Isa-VRd) | 2024 |
Sarclisa has been approved in more than 60 countries and prescribed to more than 60,000 patients worldwide. The VRd combination approved in 2024 was particularly significant: it made Sarclisa the first anti-CD38 therapy indicated with a standard-of-care triplet regimen for newly diagnosed, transplant-ineligible patients, an earlier and larger patient population than the relapsed/refractory settings covered by earlier approvals.
All three approved regimens are currently administered as intravenous infusions. The first dose of Sarclisa IV typically requires several hours; even after subsequent dose acceleration, appointments remain multi-hour commitments. For a patient who will receive Sarclisa across multiple treatment cycles, potentially for years, that time burden accumulates significantly.
What Is the On-Body Injector and Why Does It Matter?
The on-body injector (OBI) at the center of this BLA is the enFuse device, developed by Enable Injections. Understanding what it is and how it differs from standard subcutaneous injections explains both the clinical rationale and the novelty of what Sanofi is seeking to bring to market.
Standard subcutaneous injection of a biologic drug involves a healthcare provider manually pushing a syringe or autoinjector to deliver the medication into the tissue just beneath the skin. For biologics that require large volumes of fluid, manual subcutaneous injection can be uncomfortable and slow. The enFuse OBI takes a different approach.
| How the enFuse on-body injector works The enFuse is a small, flat wearable device applied to the skin surface, typically the arm, like a patch. It uses automated delivery technology to administer the drug subcutaneously at a controlled, constant rate rather than requiring manual force from a clinician. Key features: Hands-free delivery: once applied and activated, the device operates automatically and the patient can move around. Fixed dose: Sarclisa SC is given at a flat dose of 1,400 mg, eliminating the weight-based calculation required for IV dosing (10 mg/kg). Small retractable needle: thinner than current subcutaneous injection needles with low local trauma. No electronics or batteries: purely mechanical, single-use operation. Discreet: worn under clothing during administration. The device is prefilled by clinical staff and then applied to the patient. Administration time is substantially shorter than IV infusion. |
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For patients with multiple myeloma who receive treatment continuously until disease progression, the practical difference between IV and OBI administration is material. IV infusion requires a patient to sit in an infusion chair, tethered to an IV pole, for an extended period. OBI administration means the drug can be delivered while the patient is mobile, with no IV line, no infusion chair, and a substantially shorter clinic stay.
This is not cosmetic. The published literature on cancer treatment burden consistently shows that infusion-related time and logistical demands are among the leading factors affecting treatment adherence and quality of life for patients on long-term oncology regimens. A delivery format that preserves efficacy while reducing clinic time and physical constraints is a meaningful clinical advance, not merely a convenience.
The IRAKLIA Trial: What the Evidence Shows
The BLA for Sarclisa SC is supported primarily by the Phase 3 IRAKLIA study (NCT05405166), published in the Journal of Clinical Oncology and presented at the 2025 ASCO Annual Meeting and European Hematology Association Congress. IRAKLIA is the first Phase 3 myeloma trial designed to evaluate on-body injector delivery of a cancer treatment.
Study design
IRAKLIA enrolled 531 adults with relapsed/refractory multiple myeloma who had received at least one prior line of therapy including lenalidomide and a proteasome inhibitor. Patients were randomized 1:1 to:
- Sarclisa SC via OBI at 1,400 mg fixed dose plus pomalidomide plus dexamethasone (SC arm, n=263)
- Sarclisa IV at 10 mg/kg weight-based dose plus pomalidomide plus dexamethasone (IV arm, n=268)
Both arms followed the same dosing schedule: weekly for the first treatment cycle, then biweekly. The trial was designed to establish non-inferiority of the SC formulation, meaning the goal was to demonstrate that SC delivery was not meaningfully worse than IV, not that it was superior to it.
The two co-primary endpoints were objective response rate (ORR) and drug concentration at steady state (Ctrough), addressing both clinical efficacy and pharmacokinetic equivalence.
Results
| Endpoint | Sarclisa SC (OBI) | Sarclisa IV | Non-inferiority met? |
|---|---|---|---|
| ORR (overall response rate) | 71.1% | 70.5% | Yes (RR 1.008; 95% CI 0.903 to 1.126; p=0.0006) |
| Ctrough at steady state (C6D1) | GMR 1.532 (90% CI 1.316 to 1.784) | Reference | Yes (lower CI above 0.8 NI margin) |
| Ctrough at cycle 2 (key secondary) | GMR 1.302 (95% CI 1.158 to 1.465) | Reference | Yes (lower CI above 0.8 NI margin) |
| VGPR or better (key secondary) | Similar between arms | Similar between arms | Yes (NI met) |
| Infusion-related reactions | 1.5% | 25% | N/A, significant reduction favoring SC |
Source: Ailawadhi S et al. Journal of Clinical Oncology. 2025. doi:10.1200/JCO-25-00744
All four co-primary and key secondary endpoints were met. The response depth was comparable between arms, including similar rates of very good partial response (VGPR) and better, stringent complete response, and complete response. The safety profile showed no new or unexpected signals. Notably, the drug concentration in the SC arm was actually somewhat higher than in the IV arm at steady state, meaning the non-inferiority requirement was easily met from both directions.
The most striking secondary finding was the infusion-related reaction (IRR) rate: 1.5% in the SC arm versus 25% in the IV arm. Infusion reactions are one of the most common and disruptive complications of IV biologic therapy, sometimes requiring dose interruptions, premedication, prolonged monitoring, or clinical intervention. A roughly 16-fold reduction in IRR rate is clinically meaningful and directly relevant to patient experience and healthcare resource use.
Patient preference data from the companion IZALCO Phase 2 study, which evaluated Sarclisa SC with carfilzomib and dexamethasone, found that approximately 75% of patients preferred OBI delivery over manual subcutaneous injection.
The lead investigator for IRAKLIA, Dr. Xavier Leleu of Hôpital La Mileterie in Poitiers, France, characterized the trial in the JCO publication as the first Phase 3 multiple myeloma study to incorporate hands-free OBI technology, noting the implications for both practice efficiency and patient convenience.
What a Three-Month FDA Extension Actually Means
The April 22 announcement describes a standard FDA procedural action. Here is what it does and does not mean:
| What it is | What it is not |
|---|---|
| A routine extension of the PDUFA review clock by up to three months | A Complete Response Letter or rejection |
| Common for complex biologics where the FDA needs additional time to complete its review | A signal of clinical deficiency in the evidence package |
| Moves the target action date from the original deadline to July 23, 2026 | An indication that the BLA will not be approved |
| A standard regulatory mechanism used across many drug applications | Unique to Sarclisa or indicative of a problem specific to this program |
Sanofi has not disclosed the specific reason for the extension, which is typical. These extensions can arise from FDA requests for additional data or clarifications, manufacturing inspection scheduling, or the complexity of a novel delivery platform requiring more thorough review.
The most relevant context is the EU trajectory. The EMA’s CHMP issued a positive opinion recommending approval of Sarclisa SC on March 26, 2026, less than a month before the FDA extension announcement. The CHMP recommendation covers both the OBI and manual injection formats. A positive CHMP opinion nearly always results in European Commission approval, which is expected in the coming months. That the most rigorous equivalent of the FDA review process in Europe has already concluded favorably is a meaningful indicator of where the clinical package stands.
| Why the EU positive opinion matters for the U.S. review The CHMP’s positive opinion is based on the same IRAKLIA Phase 3 dataset supporting the U.S. BLA. CHMP review is scientifically independent from the FDA, conducted by a committee of European member state experts. A positive CHMP opinion based on the same evidence that the FDA is currently reviewing does not guarantee FDA approval, but it does establish that the clinical and safety package met the rigorous evidentiary standards of another leading regulatory authority. For patients and providers tracking this BLA, the EU recommendation is relevant evidence about where the clinical program stands. |
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Where This Fits in the Broader Myeloma Treatment Landscape
Multiple myeloma treatment has advanced substantially over the past decade. The introduction of proteasome inhibitors (bortezomib, carfilzomib, ixazomib), immunomodulatory drugs (lenalidomide, pomalidomide), anti-CD38 monoclonal antibodies (daratumumab, isatuximab), and more recently BCMA-directed therapies (belantamab mafodotin, teclistamab, idecabtagene vicleucel, ciltacabtagene autoleucel) has transformed a disease that once had a median survival of 2 to 3 years into one where many patients survive 10 years or longer.
With longer survival, treatment becomes a longer-term proposition, and the cumulative burden of repeated clinic visits, infusions, and associated time commitments grows accordingly. The pivot toward more convenient administration formats is a deliberate industry and clinical trend, not specific to Sarclisa.
The anti-CD38 class is the most direct competitive context. Daratumumab (Darzalex), made by Johnson and Johnson, is the dominant anti-CD38 therapy in the myeloma market and is already available in a subcutaneous formulation (Darzalex Faspro), approved in 2020. Daratumumab SC uses the Halozyme ENHANZE co-formulation with hyaluronidase, which is different from the OBI platform Sanofi is pursuing for isatuximab. Both approaches aim to solve the same clinical problem: reducing the infusion burden of IV anti-CD38 antibody therapy.
| Sarclisa SC vs. Darzalex Faspro: Comparing administration approaches Darzalex Faspro (daratumumab SC) is co-formulated with hyaluronidase-fihj, which breaks down hyaluronic acid in subcutaneous tissue to allow the drug to disperse and be absorbed. Administration is via manual subcutaneous injection, taking approximately 3 to 5 minutes. Sarclisa SC OBI would use the enFuse wearable device for automated, hands-free delivery. The fixed 1,400 mg dose eliminates weight-based calculation. The OBI technology has not been used previously for any approved anticancer therapy. If approved, Sarclisa SC OBI would be the first anticancer treatment ever delivered via on-body injector, a genuinely new delivery format in oncology, not merely an incremental modification of existing subcutaneous techniques. |
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For oncologists and hematologists managing patients on long-term anti-CD38 therapy, the choice between formulations will be influenced by institutional experience, patient preference, payer formulary structure, and dosing logistics. The clinical efficacy evidence for both daratumumab SC and isatuximab SC is strong, with non-inferiority to IV demonstrated for each. The OBI differentiator for Sarclisa is the hands-free, automated delivery format and the substantially lower infusion reaction rate (1.5% versus 25% in IRAKLIA), which may influence provider and patient preference in a competitive market.
What to Watch For: Indications and Timeline
The Sarclisa SC BLA covers all currently approved U.S. indications for the IV formulation, meaning the three approved regimens (Isa-Pd, Isa-Kd, and Isa-VRd) could all become available in the SC formulation if approved. This reflects the IRAKLIA data demonstrating consistent efficacy and safety across the pharmacokinetic parameters likely applicable to all combinations.
The revised PDUFA date is July 23, 2026. This is a target action date, not a guaranteed approval date. The FDA could approve, issue a Complete Response Letter, or request additional information by or around that date. Given the clean Phase 3 data and the EU positive opinion, the direction of the BLA appears favorable, but no approval is certain until it occurs.
The CHMP recommendation in Europe covers both the OBI and manual injection formats, meaning the EU label, if issued, will be broader than what the U.S. BLA has described publicly. Whether Sanofi plans to seek manual injection approval in the U.S. as well has not been specifically disclosed.
For patients currently on Sarclisa IV who are interested in the SC formulation, no action is needed now. If and when the FDA approves Sarclisa SC, the transition from IV to SC would be a clinical decision made with a treating hematologist, considering individual patient circumstances, tolerability, and the available combinations at that time. Clinical teams should monitor the July 23, 2026 decision window.
Multiple myeloma is a disease that most patients live with for years, and the treatment experience across those years matters as much as the clinical outcomes in any single trial. Sarclisa SC, backed by robust Phase 3 non-inferiority data and a European positive opinion, represents a meaningful step toward a less burdensome treatment experience for patients who rely on anti-CD38 therapy. The three-month FDA extension is a procedural delay, not a clinical verdict. The July 23 PDUFA date is the one to watch.
For related coverage on advances in delivery technology and oncology approvals in 2026, see our post on the first FDA approval of a subcutaneous formulation for myasthenia gravis (VYVGART Hytrulo) and our analysis of Dato-DXd and the ADC approach in triple-negative breast cancer.
Sources
Sanofi press release (FDA extension): Sanofi provides update on the regulatory submission for Sarclisa subcutaneous in the US. April 22, 2026. sanofi.com.
Sanofi press release (CHMP opinion): Sarclisa subcutaneous formulation administered via on-body injector recommended for EU approval by the CHMP. March 27, 2026. sanofi.com.
IRAKLIA Phase 3 primary publication: Ailawadhi S et al. Isatuximab Subcutaneous by On-Body Injector Versus Isatuximab Intravenous Plus Pomalidomide and Dexamethasone in Relapsed/Refractory Multiple Myeloma. Journal of Clinical Oncology. 2025. doi:10.1200/JCO-25-00744
IRAKLIA trial registration: NCT05405166. ClinicalTrials.gov.
EMA SARCLISA EPAR: Sarclisa: EPAR product information. EMA.europa.eu.
Sarclisa IV original FDA approval (Isa-Pd): FDA approves isatuximab-irfc for multiple myeloma. FDA.gov. March 2020.
Sarclisa IV approval (Isa-Kd): FDA approves isatuximab-irfc with carfilzomib and dexamethasone for relapsed/refractory multiple myeloma. FDA.gov. March 2021.
Sarclisa IV approval (Isa-VRd): FDA approves isatuximab-irfc with bortezomib, lenalidomide, and dexamethasone for newly diagnosed multiple myeloma. FDA.gov. October 2024.
Darzalex Faspro FDA approval: FDA approves daratumumab and hyaluronidase-fihj for multiple myeloma. FDA.gov. May 2020.
CancerNetwork coverage: FDA Delays Decision on Subcutaneous Isatuximab in Multiple Myeloma. cancernetwork.com. April 2026.
Targeted Oncology: IRAKLIA Trial Validates Subcutaneous Isatuximab in Multiple Myeloma. targetedonc.com.
International Myeloma Foundation: CHMP-EMA Recommends Approval of Sarclisa Subcutaneous Formulation via On-Body Injector. myeloma.org. March 2026.
Patient resources: International Myeloma Foundation | Multiple Myeloma Research Foundation | American Cancer Society: Multiple Myeloma | ClinicalTrials.gov: multiple myeloma
| Disclaimer: Health Evidence Digest provides general information about FDA regulatory updates and health research for educational purposes. This content is not a substitute for professional medical advice. Sarclisa (isatuximab-irfc) subcutaneous formulation is not currently FDA-approved; the BLA is under review with a target action date of July 23, 2026. Decisions about cancer treatment regimens should be made in consultation with a qualified, board-certified hematologist or oncologist. |
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