RegulationOrphan Drug (United States), Orphan Drug (European Union), Orphan Drug (South Korea), Orphan Drug (Australia), Priority Review (United States)

Structure/Sequence

Sequence Code 9075908L

Source: *****

Sequence Code 9075927H

Source: *****

Clinical Trials associated with Isatuximab-IRFC

NCT06832865

/ Not yet recruitingPhase 2IIT

A Phase 2 Study of Elranatamab in Combination With Isatuximab (ELISA) in Relapsed and Refractory Multiple Myeloma

This is an open-label phase 2 study of elranatamab in combination with isatuximab administered subcutaneously in patients with relapsed and refractory multiple myeloma (RRMM) who have received at least two prior lines of therapy and who have had previous treatment with both immunomodulatory drugs (IMiDs) and a proteasome inhibitor (PI). The subcutaneous injection method of isatuximab administration, including the device used to administer isatuximab, is investigational.

Start Date01 Aug 2026

Sponsor / Collaborator

The Massachusetts General Hospital

[+2]

NCT06517017

/ Not yet recruitingPhase 2IIT

Use of Isatuximab, Dexamethasone and Lenalidomide in a Go-Slow Fashion for Ultra-Frail Patients With Multiple Myeloma: A Phase 2 Multicenter Study

Historically, the frailest patients with multiple myeloma are under-represented in clinical trials, and have very high rates of treatment discontinuation, and early treatment mortality. The investigators hypothesize that a go-slow gentle approach to starting treatment in such patients, starting with just Isatuximab and dexamethasone with a gentle introduction to lenalidomide third cycle onwards, may improve treatment adherence and quality of life. The goal of this clinical trial is to learn if a go-slow approach to treating MM in ultra-frail patients may improve the ability to adhere to treatment and improve quality of life.

Start Date01 May 2025

Sponsor / Collaborator

University of Utah

[+1]

NCT06762769

/ Not yet recruitingPhase 2IIT

Isatuximab and Iberdomide As Immunotherapy for High Risk in Smouldering Myeloma

The study will test a new combination of 3 drugs: Isatuximab (Isa), Iberdomide (Iber) and Dexamethasone (Dex), in patients who have intermediate or high risk smouldering myeloma. Smouldering myeloma is an early form of myeloma which may progress to active multiple myeloma, but at a slow rate. Patients with smouldering myeloma do not usually receive any treatment but will have regular check-ups and observation. Some patients have a diagnosis of smouldering myeloma which has a higher risk of progressing to active myeloma.
The study will test if the combination of drugs is effective at preventing or delaying the disease progressing into active multiple myeloma. The study will also test if the combination is tolerated and accepted by patients.

Start Date31 Mar 2025

Sponsor / Collaborator

University College London

[+2]

100 Clinical Results associated with Isatuximab-IRFC

100 Translational Medicine associated with Isatuximab-IRFC

100 Patents (Medical) associated with Isatuximab-IRFC

437

Literatures (Medical) associated with Isatuximab-IRFC

01 Jun 2025·AMERICAN JOURNAL OF HEMATOLOGY

Belantamab Mafodotin Plus Proteasome Inhibition Efficacy Versus Comparators in Early Relapsed Myeloma: A Systematic Review and Network Meta‐Analysis

Review

Author: McNamara, Simon ; Rodríguez‐Otero, Paula ; Purser, Molly ; Sly, Indeg ; Schjesvold, Fredrik ; Katodritou, Eirini ; Ballew, Nick ; Nooka, Ajay ; Richter, Joshua ; Combe, Emily ; Cooper, Leanne ; Scott, Marianne ; Boytsov, Natalie ; Bitetti, Jacopo

ABSTRACT:

In the Phase 3 DREAMM‐7 study of patients with relapsed/refractory multiple myeloma (RRMM) who received ≥ 1 prior therapy, belantamab mafodotin plus bortezomib and dexamethasone (BVd) demonstrated a progression‐free survival (PFS) benefit versus daratumumab plus bortezomib and dexamethasone (DVd). This study aimed to indirectly compare the efficacy of BVd against alternative regimens in this patient population. A systematic literature review (SLR; December 2021–February 4, 2024) was performed to identify relevant efficacy data. Studies were selected based on the Population‐Intervention‐Comparators‐Outcomes‐Study design framework criteria and independently reviewed for inclusion in the network meta‐analysis (NMA) if they had a connection to DREAMM‐7 (approved in the US or EU, or likely to be a future DREAMM‐7 comparator). Each trial had a common comparator arm, allowing for a connected network between the trials and linkage by shared treatments. The primary analysis was PFS in the intent‐to‐treat population from each study, and secondary analyses examined other endpoints. All endpoints were also evaluated in subgroups by lenalidomide‐exposure, ‐refractoriness, and other patient characteristics. The SLR identified 12 comparator studies comprising 12 comparator regimens (each contained a proteasome inhibitor [bortezomib or carfilzomib] plus dexamethasone), all of which were included in the NMA with the DREAMM‐7 study. BVd improved PFS versus all comparators, including daratumumab plus carfilzomib and dexamethasone, isatuximab plus carfilzomib and dexamethasone, and DVd. Overall survival was also improved by belantamab mafodotin plus bortezomib and dexamethasone over the other regimens. This study provides compelling evidence for belantamab mafodotin, plus bortezomib and dexamethasone, in early lines of treatment for RRMM.

01 May 2025·JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY

Monoclonal Antibodies and Small-Molecule Inhibitors Associated Osteonecrosis of Jaw: A Retrospective Pharmacovigilance Study

Article

Author: Sridharan, Kannan ; Sivaramakrishnan, Gowri

BACKGROUND:

Osteonecrosis of the jaw (ONJ) is an adverse effect associated with medications such as monoclonal antibodies and small-molecule inhibitors.

PURPOSE:

This study assesses the association between monoclonal antibodies and small-molecule inhibitors with ONJ.

STUDY DESIGN, SETTING, SAMPLE:

The study design was a retrospective pharmacovigilance case series. The sample was derived from the United States Food and Drug Administration Adverse Event Reporting System database reporting ONJ from March 2004 to March 2024. The inclusion criteria were the reports relating ONJ occurrence with exposure to monoclonal antibodies (trastuzumab, bevacizumab, denosumab, elotuzumab, isatuximab, pertuzumab, ramucirumab, romosozumab, and ado-trastuzumab emtansine) and small-molecule inhibitors (abemaciclib, alpelisib, axitinib, cabozantinib, lapatinib, lenvatinib, palbociclib, ribociclib, and sunitinib). The exclusion criteria were the reports associating the role of monoclonal antibodies and small molecule inhibitors to ONJ with roles other than primary suspicion.

PREDICTOR VARIABLE:

Not applicable.

MAIN OUTCOME VARIABLE:

The outcome variable is the case status divided into case and noncase. Cases were defined as reports with ONJ associated with monoclonal antibodies or small-molecule inhibitors while noncases were the reports with other adverse events. Secondary outcome variables were death, hospitalization, and disability observed with monoclonal antibodies/small-molecule inhibitors-associated ONJ.

COVARIATES:

Age and gender were the covariates included in this study.

ANALYSES:

The case-noncase approach was applied for signal detection, using frequentist (reporting odds ratio [ROR] and proportional reporting ratio [PRR]) and Bayesian methods (lower limit of 95% CI of Information component [IC025]). The ROR is determined by comparing the odds of ONJ being reported for a given drug to the odds of the same event being reported for all other drugs and PRR is estimated by the ratio of proportion of reports for a specific drug with ONJ over the proportion of reports with ONJ for all other drugs. The information component is defined as defined as the logarithmic ratio of the observed ONJ with the primary suspected drug relative to the expected frequency of the drug-ONJ pair based on overall reporting rates in the database. Outcomes were analyzed with statistical comparisons using χ² tests (χ2) at P ≤ .05.

RESULTS:

A total of 7,402 reports were included with median age ranging between 61 and 76 years with female preponderance. Denosumab (ROR: 64.7 [62.5, 67]; PRR: 61.9 [59.9, 64.1]; P < .05; and IC025: 5.1), romosozumab (ROR 4.2 [3, 6]; PRR: 4.2 [3, 6]; P < .05; and IC025: 1.5), and lenvatinib (ROR: 3.1 [2.3, 4.2]; PRR: 3.1 [2.3, 4.1]; P < .05; and IC025: 1.2) showed positive signals for ONJ compared to all other drugs in the database by both frequentist and Bayesian analyses indicating a potential association. Sixty-two point eight percent cases resulted in hospitalization and was no significant differences were observed in the distribution of outcomes between the monoclonal antibodies and small molecule inhibitors (χ²: 12; df: 14; P = .6). The risk was mainly observed in elderly and female patients.

CONCLUSION AND RELEVANCE:

Denosumab, romosozumab, and lenvatinib are significantly associated with ONJ, particularly in older and female patients. Further research is needed to understand the mechanisms and improve risk management strategies.

01 May 2025·International Journal of Clinical Oncology

PMDA regulatory update on approval and revision of the precautions for use of anticancer drugs; approval of atezolizumab for alveolar soft part sarcoma, epcoritamab for follicular lymphoma, and isatuximab for multiple myeloma in Japan

Author: Matsumura, Noriomi ; Mandai, Masaki

223

News (Medical) associated with Isatuximab-IRFC

03 Jun 2025

·www.globenewswire.com

Press Release: ASCO: new Sarclisa data support subcutaneous administration with on-body injector

ASCO: new Sarclisa data support subcutaneous administration with on-body injector New data from two clinical studies demonstrated that Sarclisa administered subcutaneously via an investigational on-body injector shortened treatment time to minutes with similar efficacy and safety compared to intravenous infusionStudies used Enable Injections’ enFuse® on-body injector, an automated hands-free injectorData will form the basis of global regulatory submissions across all currently approved lines of treatment Paris, June 3, 2025. New data from two clinical studies of the investigational use of Sarclisa administered subcutaneously (SC) via an on-body injector (OBI) (also referred to as an on-body delivery system) in relapsed or refractory multiple myeloma (R/R MM) support the potential use of this innovative delivery method to advance patient care, while upholding Sarclisa’s efficacy and safety profile. The results were presented at the American Society of Clinical Oncology (ASCO) Annual Meeting and include full data from the IRAKLIA phase 3 study, the first to incorporate the use of an OBI in the treatment of MM, and demonstrate non-inferior efficacy and pharmacokinetics compared to Sarclisa intravenous (IV) infusion. Alyssa Johnsen, MD, PhDGlobal Therapeutic Area Head, Immunology and Oncology Development “Our subcutaneous clinical program is rooted in our mission to address patient needs and reduce treatment burden in multiple myeloma. We believe the novel on-body injector represents a significant innovation that could improve and streamline the treatment process for both patients and providers. We are pleased to share these data, the first to evaluate an on-body injector with a multiple myeloma treatment, and look forward to potentially bringing this formulation and administration option to the multiple myeloma community.” The OBI offers the potential to improve the overall patient experience in MM treatment. Recent studies and surveys suggest the use of an OBI may be associated with greater convenience, flexibility, and patient satisfaction compared to IV or manual SC administration methods.1 In addition, an OBI may also streamline the administration process for providers, potentially reducing the physical burden on nurses and enabling them to possibly move freely through the use of a hands-free device while monitoring the patient during injection. The IRAKLIA phase 3 study and the IZALCO phase 2 study presented at ASCO were conducted using Enable Injections’ enFuse® hands-free OBI, an automated injector designed to subcutaneously administer high-volume medicines beginning with the click of a button, to administer the hyaluronidase-free SC formulation of Sarclisa. The enFuse device uses a 30 gauge, hidden, and retractable needle that is smaller compared to some of the commonly used large-volume SC injection needles, which may support patient comfort. The safety and efficacy of Sarclisa SC administered with the OBI or manual administration are investigational and have not been approved for use by any regulatory authority. IRAKLIA phase 3 study IRAKLIA is a global, randomized, open-label, pivotal phase 3 non-inferiority study comparing Sarclisa SC administered via an OBI and Sarclisa IV, both in combination with pomalidomide and dexamethasone (Pd) in adult patients with R/R MM who have received at least one prior line of treatment. At the data cut-off of November 6, 2024, and a median follow-up of 12 months, the study demonstrated: Primary endpoints Objective response rate (ORR) with Sarclisa SC-Pd was 71.1% compared to 70.5% with Sarclisa IV-Pd, establishing non-inferiority (risk ratio [RR] 1.008; 95% confidence interval [CI]: 0.903-1.126; p=0.0006).Observed Sarclisa mean (standard deviation [SD]) concentration before dosing (C trough) at steady state (C6D1 pre-dose) with Sarclisa SC-Pd was 499 (259) ug/mL compared to 341 (169) ug/mL with Sarclisa IV-Pd, establishing non-inferiority (geometric mean ratio [GMR] 1.532; 90% CI: 1.316-1.784). Secondary endpoints Very good partial response (VGPR) or better rates were consistent between Sarclisa SC-Pd and Sarclisa IV-Pd at 46.4% and 45.9%, respectively (RR 1.011; 95% CI: 0.841-1.215; p<0.0001).Observed Sarclisa mean (SD) C trough at 4 weeks (C2D1 pre-dose) with Sarclisa SC-Pd was 421 (215) ug/mL compared to 302 (117) ug/mL with Sarclisa IV-Pd (GMR 1.302; 90% CI 1.158-1.465).Systemic infusion reactions (IR) were significantly lower with Sarclisa SC-Pd, occurring in only 1.5% of patients compared to 25% of those treated with Sarclisa IV-Pd (RR: 0.061; 95% CI: 0.022-0.164; p<0.0001). Of note, nearly all IRs occurring were grade 1 or 2 and resolved within one day. No patients in the Sarclisa SC-Pd arm discontinued treatment due to a systemic IR.Most Sarclisa SC-Pd-treated patients (70%) reported being satisfied or very satisfied with their injection compared to 53.4% in the Sarclisa IV-Pd arm, demonstrating the positive impact of this innovative method of administration on the patient experience (OR 2.036; 95% CI: 1.425-2.908; p=0.0001).99.9% of Sarclisa SC OBI injections were successfully delivered with no significant safety concerns related to the OBI.Progression-free survival (PFS) rates at 12 months were also similar, reaching 66.1% for patients treated with Sarclisa SC-Pd compared to 65.1% of patients treated with Sarclisa IV-Pd (HR 0.985; 95% CI: 0.726-1.338). The overall safety profile of Sarclisa SC-Pd observed in this study was consistent with the established safety profile of Sarclisa IV-Pd, but with a notably lower rate of systemic IRs. No new safety concerns were observed, except for low-grade local injection site reactions (ISRs) associated with SC administration that occurred with a low incidence (0.4%, n=19/5,145 injections). Nearly all ISRs were grade 1, except for one episode of grade 2. Xavier Leleu, MD, PhDHead of the Department of Hematology and Myeloma Clinic at the Hôpital La Mileterie and study investigator“Results from the IRAKLIA phase 3 study represent a potentially transformational advancement in the administration of multiple myeloma treatment. These data not only establish non-inferiority between Sarclisa administered both subcutaneously and intravenously across several key endpoints but reinforce the positive impact that this on-body injector could have on the patient treatment experience, as demonstrated by patient satisfaction scores.” In addition to the oral presentation at ASCO, the full data were simultaneously published in the Journal of Clinical Oncology. IZALCO phase 2 studyIn addition to the IRAKLIA phase 3 study, Sanofi also presented new data from the randomized, sequential, open-label, IZALCO phase 2 study evaluating the efficacy and safety of Sarclisa SC administered via manual push or an OBI, in combination with carfilzomib and dexamethasone (Kd) in adult patients with R/R MM who have received one to three prior lines of therapy. At a median follow-up of 10.1 months, the study demonstrated: ORR was 79.7% in patients treated with Sarclisa SC-Kd (95% CI: 68.8-88.2) validating the prespecified efficacy hypothesis. With a median follow-up of 10 months, VGPR or better rate in patients treated with Sarclisa SC-Kd was 62.2% and complete response (CR) or better rate was 21.6%.Only two patients treated with Sarclisa SC-Kd, or 2.7% of recipients, experienced a grade 2 or lower IR event with manual injection and no IR event occurred with OBI administration; approximately 1% of injections were associated with a local ISR.After treatment with both methods, most patients (74.5%) preferred the OBI versus 17% who preferred manual injection and 8.5% with no preference (p=0.0004; binomial test against the null hypothesis of ≤50% rate). The overall safety profile of Sarclisa SC-Kd observed in this study was consistent with the established safety profile of Sarclisa IV-Kd, with no new safety concerns observed. Advancing patient and provider-centric innovation in MM While SC administration is currently available for certain MM treatment regimens through a manual injection, administering large-volume medicines manually can present significant challenges, including a labor-intensive process for nurses, risk of strain and needlestick injuries, and potential need for larger needles that may compromise patient comfort and increase anxiety. Mehul Desai, PharmD, MBAVice President, Medical Affairs, Enable Injections “We believe multiple myeloma patients deserve a more convenient and comfortable treatment experience and recognize the crucial role providers play in delivering that care. Through our collaboration with Sanofi, we’ve aspired to advance an on-body injector that could transform the treatment experience for patients and providers alike. The results from the IRAKLIA and IZALCO studies represent a significant step toward our ambition and validate the potential of the on-body injector to deliver the same high standard of efficacy established with intravenous Sarclisa.” In addition to IRAKLIA and IZALCO, Sanofi is also evaluating Sarclisa SC administration via an OBI in the front-line treatment setting. The ISASOCUT phase 2 study conducted by the University of Poitiers, is evaluating Sarclisa in combination with bortezomib, lenalidomide and dexamethasone (VRd) in adult patients with newly diagnosed MM (NDMM) not eligible for autologous stem-cell transplant (ASCT), while the German-speaking Myeloma Multicenter Group (GMMG)-HD8 phase 3 study, conducted in collaboration with the GMMG and the German Multiple Myeloma Study Group Consortium (DSMM), is evaluating Sarclisa SC-VRd induction in NDMM patients who are eligible for ASCT. In addition, results from the IZALCO, IRAKLIA and ISASOCUT studies will be presented at the European Hematology Association Congress later this month. The IRAKLIA abstract was also hand-selected to be included in the 2025 Best of ASCO program, held later in the summer of 2025, following the ASCO Annual Meeting. The data from these studies, collectively, will form the basis for global regulatory submissions. Sarclisa administered subcutaneously via the on-body injector or manual administration is investigational and has not been approved for any use by any regulatory authority. The safety and efficacy of this formulation and delivery method have not been established. About the IRAKLIA and IZALCO studiesIRAKLIA is a randomized, open-label, pivotal phase 3 study evaluating the non-inferiority of Sarclisa SC formulation administered at a fixed dose SC via an OBI versus weight-based dosed Sarclisa IV in combination with Pd in adult patients with R/R MM who have received at least one prior line of therapy. The co-primary outcomes being assessed are ORR, defined as the proportion of patients with stringent CR, CR, VGPR, and partial response (PR) according to the 2016 IMWG criteria assessed by Independent Review Committee (IRC), and observed C trough at steady state (pre-dose at C6D1), defined as observed Sarclisa plasma concentrations. IZALCO is a two-part, randomized, sequential, open-label, phase 2 study evaluating the efficacy and safety of Sarclisa SC formulation administered SC via manual push or an OBI in adult patients with R/R MM who have received one to three prior lines of therapy. The primary objective is ORR, as assessed by IRC. The secondary objective is patient preference for the OBI versus manual administration of Sarclisa SC. About Enable Injections Based in the US (Cincinnati, OH), Enable Injections is a global healthcare innovation company committed to improving the patient treatment experience through the development and manufacturing of enFuse. enFuse is an innovative wearable drug delivery platform that is designed to deliver large volumes of pharmaceutical and biologic therapeutics via subcutaneous administration, with the aim of improving convenience, supporting superior outcomes, and advancing healthcare system economics. For more information, visit https://enableinjections.com. About SarclisaSarclisa (isatuximab) is approved in more than 50 countries, including in the US, EU, Japan, and China, across multiple treatment lines for MM. Based on the ICARIA-MM phase 3 study, Sarclisa is approved in the US, EU and Japan in combination with Pd for the treatment of patients with R/R MM who have received ≥two prior therapies, including lenalidomide and a proteasome inhibitor and have relapsed on the last therapy; this combination is also approved in China for patients who have received at least one prior line of therapy, including lenalidomide and a proteasome inhibitor. Based on the IKEMA phase 3 study, Sarclisa is also approved in more than 50 countries in combination with carfilzomib and dexamethasone, including in the US for the treatment of patients with R/R MM who have received one to three prior lines of therapy and in the EU for patients with MM who have received at least one prior therapy. In the US, EU, UK, and China, Sarclisa is approved in combination with VRd as a front-line treatment option in transplant-ineligible NDMM patients, based on the IMROZ phase 3 study. In Japan, Sarclisa is approved in combination with VRd as a front-line treatment option regardless of transplant eligibility. At Sanofi, we are building on a long-standing commitment to oncology as we continue to chase the miracles of science to improve the lives of those living with cancer. We are committed to transforming cancer care by developing innovative, first and best-in-class immunological and targeted therapies for rare and difficult-to-treat cancers with high unmet need. For more information on Sarclisa clinical studies, please visit www.clinicaltrials.gov. About Sanofi Sanofi is an R&D driven, AI-powered biopharma company committed to improving people’s lives and creating compelling growth. We apply our deep understanding of the immune system to invent medicines and vaccines that treat and protect millions of people around the world, with an innovative pipeline that could benefit millions more. Our team is guided by one purpose: we chase the miracles of science to improve people’s lives; this inspires us to drive progress and deliver positive impact for our people and the communities we serve, by addressing the most urgent healthcare, environmental, and societal challenges of our time. Sanofi is listed on EURONEXT: SAN and NASDAQ: SNY Media RelationsSandrine Guendoul | +33 6 25 09 14 25 | sandrine.guendoul@sanofi.com Evan Berland | +1 215 432 0234 | evan.berland@sanofi.com Léo Le Bourhis | +33 6 75 06 43 81 | leo.lebourhis@sanofi.com Victor Rouault | +33 6 70 93 71 40 | victor.rouault@sanofi.comTimothy Gilbert | +1 516 521 2929 | timothy.gilbert@sanofi.com Investor RelationsThomas Kudsk Larsen |+44 7545 513 693 | thomas.larsen@sanofi.com Alizé Kaisserian | +33 6 47 04 12 11 | alize.kaisserian@sanofi.comFelix Lauscher | +1 908 612 7239 | felix.lauscher@sanofi.com Keita Browne | +1 781 249 1766 | keita.browne@sanofi.comNathalie Pham | +33 7 85 93 30 17 | nathalie.pham@sanofi.comTarik Elgoutni | +1 617 710 3587 | tarik.elgoutni@sanofi.com Thibaud Châtelet | +33 6 80 80 89 90 | thibaud.chatelet@sanofi.com Yun Li | +33 6 84 00 90 72 | yun.li@sanofi.com Sanofi forward-looking statementsThis press release contains forward-looking statements as defined in the Private Securities Litigation Reform Act of 1995, as amended. Forward-looking statements are statements that are not historical facts. These statements include projections and estimates regarding the marketing and other potential of the product, or regarding potential future revenues from the product. Forward-looking statements are generally identified by the words “expects”, “anticipates”, “believes”, “intends”, “estimates”, “plans”, and similar expressions. Although Sanofi’s management believes that the expectations reflected in such forward-looking statements are reasonable, investors are cautioned that forward-looking information and statements are subject to various risks and uncertainties, many of which are difficult to predict and generally beyond the control of Sanofi, that could cause actual results and developments to differ materially from those expressed in, or implied or projected by, the forward-looking information and statements. These risks and uncertainties include among other things, unexpected regulatory actions or delays, or government regulation generally, that could affect the availability or commercial potential of the product, the fact that product may not be commercially successful, the uncertainties inherent in research and development, including future clinical data and analysis of existing clinical data relating to the product, including post marketing, unexpected safety, quality or manufacturing issues, competition in general, risks associated with intellectual property and any related future litigation and the ultimate outcome of such litigation, and volatile economic and market conditions, and the impact that global crises may have on us, our customers, suppliers, vendors, and other business partners, and the financial condition of any one of them, as well as on our employees and on the global economy as a whole. The risks and uncertainties also include the uncertainties discussed or identified in the public filings with the SEC and the AMF made by Sanofi, including those listed under “Risk Factors” and “Cautionary Statement Regarding Forward-Looking Statements” in Sanofi’s annual report on Form 20-F for the year ended December 31, 2024. Other than as required by applicable law, Sanofi does not undertake any obligation to update or revise any forward-looking information or statements. All trademarks mentioned in this press release are the property of the Sanofi group with the exception of enFuse. Attachment Press Release

Phase 3Clinical ResultDrug ApprovalPhase 2ASCO

03 Jun 2025

·firstwordpharma.com

ASCO25: Sanofi details Sarclisa on-body injector data as it chases after Darzalex's lead

Sanofi presented positive clinical data Tuesday for a subcutaneous (SC) formulation of its multiple myeloma drug Sarclisa (isatuximab) at the American Society of Clinical Oncology (ASCO) annual meeting, offering hope for the French drugmaker's efforts to grab more market share from Johnson & Johnson's dominant Darzalex (daratumumab) franchise.While Darzalex generated $11.7 billion in sales last year compared to Sarclisa's $471 million, the new data suggest Sanofi's SC approach – using an on-body injector – could help level the playing field in a market for CD38-targeting drugs that Sanofi estimates will reach €16 billion ($18.2 billion) by 2030 (see – Spotlight On: J&J's Darzalex joins the $10 billion club).The Phase III IRAKLIA study, toplined earlier this year, showed that Sarclisa administered subcutaneously via Enable Injections' enFuse on-body injector achieved a 71.1% objective response rate (ORR) after a median follow-up of 12 months, compared to 70.5% for the current intravenous (IV) formulation, meeting the non-inferiority primary endpoint. IRAKLIA tested both versions in combination with pomalidomide and dexamethasone in adult patients with relapsed/refractory multiple myeloma who have received at least one prior line of treatment.Thin, retractable needleThe automated hands-free device uses a 30-gauge hidden and retractable needle that is thinner than commonly used SC injection needles. Sanofi said systemic infusion reactions in the study dropped significantly to just 1.5% of patients receiving the SC formulation versus 25% for IV administration.Patient satisfaction scores also favoured the SC approach, with 70% reporting they were satisfied or very satisfied compared to 53.4% for IV treatment. Progression-free survival rates at 12 months were similar between the two formulations at 66.1% and 65.1%, respectively.Meanwhile, data from the Phase II IZALCO study evaluating Sarclisa SC via manual push or an on-body injector in combination with carfilzomib and dexamethasone in patients who had received one to three prior lines of therapy showed a 79.7% ORR. When comparing delivery methods within the SC approach, 74.5% of patients preferred the on-body injector whereas only 17% favoured manual injection.Darzalex's five-year lead "We believe the novel on-body injector represents a significant innovation that could improve and streamline the treatment process for both patients and providers," said Alyssa Johnsen, Sanofi's global therapeutic area head for immunology and oncology development. The company has said the first regulatory submissions are expected this half.Sanofi's subcutaneous programme received financial backing from Blackstone Life Sciences, which committed up to €300 million ($341 million) in 2022 through a risk-sharing agreement that makes the investment firm eligible for royalties on future subcutaneous sales.The drugmaker is looking to challenge J&J's market domination in multiple myeloma with Darzalex, which was first approved in 2015. An SC version of J&J's drug, that uses Halozyme's ENHANZE drug-delivery technology and is sold under the name Darzalex Faspro (daratumumab/hyaluronidase-fihj), has been cleared since 2020. Unlike Darzalex Faspro, Sarclisa SC is hyaluronidase-free.Last month, an FDA advisory panel recommended that Darzalex Faspro be approved for a new indication – high-risk smouldering multiple myeloma.Despite J&J's head start, Brian Foard, Sanofi's head of specialty care, expressed confidence during a January earnings call in Sarclisa SC's competitive prospects. "We absolutely do not think it's too late. We absolutely believe we have all of the elements we need now to compete in the marketplace," Foard said. "We are investing behind this asset as we said before, and we believe it's going to be a multi blockbuster."

Clinical ResultDrug ApprovalPhase 3ASCOPhase 2

02 Jun 2025

·www.prnewswire.com

Full Dose-Escalation Data Show Continued High Response Rates and Favorable Safety Profile of ISB 2001, a First-in-Class BCMA × CD38 × CD3 Trispecific Antibody, for the Treatment of Relapsed/Refractory Multiple Myeloma

TRIgnite-1 study shows an overall response rate (ORR) of 74% across nine dose levels, in heavily pretreated patients with a median of six prior lines of therapy ORR is remarkably high in patients with no prior CAR-T or bispecific therapies (84%) as well as in patients who had received prior T cell- targeted therapies, prior BCMA-targeted therapies, or were refractory to anti-CD38 therapy (range: 71–73%) Safety profile continues to be favorable, with the majority of patients remaining on treatment at data cutoff FDA recently granted ISB 2001 Fast Track Designation NEW YORK, June 2, 2025 /PRNewswire/ -- Ichnos Glenmark Innovation (IGI), a global, fully integrated clinical-stage biotechnology company focused on developing multispecifics™ in oncology, today presented promising full dose-escalation results from its Phase 1 TRIgnite-1 study of ISB 2001, an investigational first-in-class BCMA × CD38 × CD3-targeting trispecific antibody for the treatment of patients with relapsed or refractory multiple myeloma (RRMM). These data, presented as a rapid oral presentation (Abstract #7514) at the American Society of Clinical Oncology (ASCO) 2025 Annual Meeting, demonstrated a sustained overall response rate (ORR) of 79% and a high complete/stringent complete response (CR/sCR) rate of 30% across seven active dose levels (≥ 50 µg/kg) in a heavily pretreated patient population, with a favorable safety profile. The ORR was 74% in all treated patients, including two patients treated at lower dose levels. ISB 2001 was designed to simultaneously target multiple myeloma by binding to the tumor- associated antigens BCMA and CD38, even when expressed at low levels, while engaging T cells to trigger an immune response. This novel trispecific design enhances tumor-specific cytotoxicity and aims to overcome resistance mechanisms seen with first-generation bispecific antibodies and CAR T-cell therapies, while minimizing off-tumor toxicity. Professor Hang Quach, M.D., Professor of Haematology at the University of Melbourne and Director of Haematology at St. Vincent's Hospital Melbourne, said "Responses to ISB 2001 highlight the remarkable anti-myeloma activity of this first-in-class anti BCMA × CD38 × CD3 trispecific antibody-T cell engager in heavily pretreated RRMM patients, including those who have exhausted prior T cell-redirecting, BCMA-targeted, or anti-CD38 therapies - an especially challenging, quad-exposed patient population. With its unprecedented potency and tolerability, ISB 2001 has the potential to redefine the treatment landscape for RRMM, offering new hope for patients with limited therapeutic options." A total of 35 patients with at least one month of follow-up had received a median of six prior lines of therapy (range: 3–11) at study entry, underscoring a heavily pretreated population. ISB 2001 demonstrated high response rates at active dose levels, with 33 patients treated at ≥ 50 µg/kg (dose levels 3–9). Responses were durable and deepened over time, irrespective of prior lines of therapy or refractoriness status, reinforcing the strength of earlier findings reported at ASH 2024 Annual Meeting in 18 patients treated with ISB 2001 at doses ≥ 50 µg/kg: The ORR was 79% (26/33), including a CR/sCR rate of 30% (10/33), with a median follow- up of 6.3 months (range: 1–16). Of the 10 patients achieving CR/sCR, eight were evaluable for minimal residual disease (MRD), and six achieved MRD negativity, indicating no detection of myeloma cells by molecular or flow cytometry assays with 10-5 sensitivity, and reinforcing the depth of response. Among 25 patients refractory to anti-CD38 therapies, the ORR was 72%, with a CR/sCR rate of 24%. In 19 patients without prior T-cell directed therapy (TCDT), including bispecific antibodies and/or CAR T-cell therapy, the ORR was 84%, with CR/sCR rate of 32%. Among 14 patients previously treated with TCDT, the ORR remained strong at 71% with a CR/sCR rate of 28%. In 15 patients who had received prior BCMA-targeted therapies, the ORR was 73%, with a CR/sCR rate of 27%. The median half-life of ISB 2001 was approximately 17 days, supporting the potential for less-frequent dosing. ISB 2001 demonstrated a favorable safety profile throughout the dose-escalation phase, with no dose-limiting toxicities (DLTs) reported. Cytokine release syndrome (CRS) occurred in 24 patients (69%), primarily Grade 1, with only four patients experiencing Grade 2 events. CRS was mostly limited to the first administration of ISB 2001, and no severe or life-threatening cases were observed. Drug-related severe infections were infrequent (4 patients, 11%), with no Grade 4 or higher infection. One patient experienced Grade 1 ICANS; no other drug-related neurologic adverse events were reported. The dose-expansion portion of the Phase 1 study is ongoing to establish the recommended Phase 2 dose (RP2D) and the best dosing schedule to enable the first registrational study with ISB 2001. "The high response rates and low safety concerns demonstrated in the dose-escalation portion of the TRIgnite-1 study, conducted in a heavily pretreated population across multiple types of therapies, reinforce the promise of ISB 2001 as a potential new treatment for patients," said Lida Pacaud, M.D., Chief Medical Officer at IGI. "As we advance to the second part of the TRIgnite-1 study, our focus is now on defining the recommended dosing schedule and evaluating ISB 2001 in a larger population of heavily pretreated RRMM patients, where we hope to observe similarly impressive treatment responses and tolerability." About TRIgnite-1 TRIgnite-1 (NCT05862012) is an ongoing Phase 1, first-in-human, open-label, multicenter study evaluating the safety and anti-myeloma activity of ISB 2001 in patients with RRMM. The dose- escalation study enrolled patients with RRMM who were treated with immunomodulatory drugs, proteasome inhibitors, and anti-CD38 monoclonal antibodies and are refractory to, or intolerant of, established therapies known to provide clinical benefit in multiple myeloma. Patients with prior CAR-T cell therapies, bispecifics and/or prior BCMA targeted agents were eligible. The TRIgnite-1 study has two parts: dose escalation and dose expansion. The dataset presented comes from patients treated in the entire dose-escalation portion who have at least 1-month follow-up at six sites in the United States and Australia. The dose-expansion study is randomized, compliant with Project Optimus at the U.S. Food and Drug Administration (FDA), and is underway in the U.S. and Australia, with European enrollment beginning soon. About ISB 2001 and Relapsed/Refractory Multiple Myeloma ISB 2001 is a first-in-class trispecific T-cell engager that targets BCMA and CD38 on myeloma cells and CD3 on T cells. Developed using IGI's proprietary BEAT® protein platform, ISB 2001 was engineered with two distinct binders against myeloma-associated antigens to enhance avidity, even at low target expression levels, while aiming to improve safety over first-generation bispecific antibodies. The U.S. Food and Drug Administration (FDA) granted ISB 2001 Fast Track Designation in May 2025 and Orphan Drug Designation in July 2023. Nearly all patients with RRMM ultimately experience disease progression. With no cure currently available and limited treatment options once approved therapies are exhausted, there remains a significant unmet need. IGI is developing ISB 2001 to address this gap, specifically for patients who have previously received T-cell–directed therapies, including CAR T-cell treatments and bispecific antibodies. About IGI IGI is a global, fully integrated clinical-stage biotechnology company focused on developing innovative biologics in oncology. Headquartered in New York, NY, IGI is advancing a robust pipeline of novel, first-in-class multispecifics™ aimed at addressing complex diseases and treating patients holistically. Powered by its proprietary BEAT® technology platform, IGI is committed to delivering breakthrough, curative therapies to improve and extend the lives of patients battling hematological malignancies and solid tumors. For more information, visit Logo - SOURCE Ichnos Glenmark Innovation WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Clinical ResultFast TrackPhase 1Cell TherapyASCO

100 Deals associated with Isatuximab-IRFC

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KEGG	Wiki	ATC	Drug Bank
-	Isatuximab-IRFC	L01	DB14811

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Relapse multiple myeloma	Japan	Sanofi KK	29 Jun 2020
Multiple Myeloma	United States	Sanofi-Aventis U.S. LLC	02 Mar 2020

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Residual Neoplasm	Phase 3	Belgium	Amgen, Inc.	08 Dec 2021
Residual Neoplasm	Phase 3	Belgium	Sanofi	08 Dec 2021
Residual Neoplasm	Phase 3	Belgium	Bristol Myers Squibb Co.	08 Dec 2021
Residual Neoplasm	Phase 3	France	Sanofi	08 Dec 2021
Residual Neoplasm	Phase 3	France	Amgen, Inc.	08 Dec 2021
Residual Neoplasm	Phase 3	France	Bristol Myers Squibb Co.	08 Dec 2021
Residual Neoplasm	Phase 3	Réunion	Bristol Myers Squibb Co.	08 Dec 2021
Residual Neoplasm	Phase 3	Réunion	Amgen, Inc.	08 Dec 2021
Residual Neoplasm	Phase 3	Réunion	Sanofi	08 Dec 2021
Smoldering Multiple Myeloma	Phase 3	United States	Sanofi-Aventis Deutschland GmbH	16 Jun 2020

Clinical Result

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT05405166 (IRAKLIA, Company_Website) Manual	Phase 3	Multiple Myeloma	-	Sarclisa SC + pomalidomide + dexamethasone	cbqlxptdyz(kopppujclc) = met its co-primary endpoints of non-inferior objective response rate (ORR) and observed concentration before dosing (C trough). uhcrijszko (kcajrphnow ) Met View more	Positive	09 Jan 2025
				Sarclisa IV + pomalidomide + dexamethasone
NCT04939844 (REST, ASH2024) Manual	Phase 2	Multiple Myeloma First line	51	Isatuximab+Bortezomib+Lenalidomide+Dexamethasone	kjndtognes(jxplurotsw) = gfmwqwbfki emtczwhtgt (ghhhsqtewh ) View more	Positive	09 Dec 2024
NCT03319667 (IMROZ, ASH2024) Manual	Phase 3	Multiple Myeloma First line	446	Isatuximab, Bortezomib, Lenalidomide, and Dexamethasone (Isa-VRd)	xbcpivhkhy(rqjhodmvtx) = cdpsbrnnso nvhpucyajj (giycuzrizc ) View more	Positive	09 Dec 2024
				Bortezomib, Lenalidomide, and Dexamethasone (VRd)	xbcpivhkhy(rqjhodmvtx) = zutwuktquw nvhpucyajj (giycuzrizc ) View more
ASH2024 Manual	Not Applicable	Refractory Multiple Myeloma	83	isatuximab + pomalidomide + dexamethasone	eitrzbaqdn(wehblzvksf) = xzhbmejkfy mzxulopvkj (lxvlxjwgxm ) View more	Positive	08 Dec 2024
				isatuximab + pomalidomide + dexamethasone (patients with intraosseous components)	ihhszldwno(kzaxnpmdgv) = okukewzagt hbvycdlmak (tjnciqasoh ) View more
NCT02332850 (ASH2024) Manual	Phase 2	Multiple Myeloma	50	IsatuximabCarfilzomibDexamethasone	zhimdfysak(uidgflvlsg) = ffbbhhcclh ychllywwti (vlmkgrsavi ) View more	Positive	07 Dec 2024
NCT03319667 (IMROZ, Pubmed \| N Engl J Med)	Phase 3	Multiple Myeloma First line	446	Isatuximab plus VRd	mmarpxenkc(xmsripiale) = hsdjghspqw rpvgrralmw (bbfyauwnio ) View more	Positive	31 Oct 2024
				VRd alone	mmarpxenkc(xmsripiale) = grkxkyyjjd rpvgrralmw (bbfyauwnio ) View more
NCT04083898 (Pubmed \| Ann Hematol) Manual	Phase 1	Multiple Myeloma	15	Isatuximab bendamustineprednisone	gcgzhabthx(zdjdqgrkwy) = sssiofvbio tgxohrjgme (gnzmnouvsk ) View more	Positive	04 Sep 2024
NCT04661033 (CTgov)	Phase 2	Warm autoimmune hemolytic anemia	8	Isatuximab SAR650984 (Part A: Cohort 1: Isatuximab 140 mg SC Q2W x2)	beshsfbnti = rxlliinykn cxolukxcwd (sfuwojvmyr, anqriwpipo - fytozvpuwm) View more	-	27 Aug 2024
				Isatuximab SAR650984 (Part A: Cohort 2: Isatuximab 280 mg SC Q2W x6)	beshsfbnti = ijmssfbvel cxolukxcwd (sfuwojvmyr, pirniieirz - joakgrujwm) View more
NCT03319667 (IMROZ, ASCO2024) Manual	Phase 3	Multiple Myeloma First line anti-CD38 monoclonal antibody	446	Isatuximab, bortezomib, lenalidomide, and dexamethasone (Isa-VRd)	ptitdhoynq(usbeozjoti) = ikfnzleyqg plekcadbgc (oljcbquyls, 0.406 - 0.876) View more	Positive	24 May 2024
				bortezomiblenalidomidedexamethasone	ptitdhoynq(usbeozjoti) = ibnyacukfj plekcadbgc (oljcbquyls ) View more

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