Isatuximab
- Generic Name
- Isatuximab
- Brand Names
- Sarclisa
- Drug Type
- Biotech
- CAS Number
- 1461640-62-9
- Unique Ingredient Identifier
- R30772KCU0
- Background
Isatuximab (formerly SAR650984) is a humanized, IgG1-derived monoclonal antibody (mAb) produced from a Chinese hamster ovary (CHO) cell line. Structurally, isatuximab is comprised of two identical immunoglobulin kappa light chains and two identical immunoglobulin gamma heavy chains. It is a cytolytic antibody targeted against CD38, a glycoprotein found on the surface of some immune cells that is highly expressed by malignant plasma cells in multiple myeloma. Along with daratumumab, another anti-CD38 mAb, isatuximab constitutes a novel treatment modality for patients with difficult-to-treat multiple myeloma.
Following three consecutive years on the yearly "Antibodies to watch" list published in "mAb", a peer-reviewed scientific journal dedicated to antibody research, isatuximab was granted Orphan Drug designation and approved on March 2nd, 2020, for the treatment of multiple myeloma. It is manufactured by Sanofi-Aventis U.S. under the brand name Sarclisa.
- Indication
Isatuximab is indicated in combination with pomalidomide and dexamethasone for the treatment of multiple myeloma in adults who have received at least two prior therapies including lenalidomide and a proteasome inhibitor. It is also indicated in combination carfilzomib and dexamethasone for the treatment of adult patients with relapsed or refractory multiple myeloma who have received 1 to 3 prior lines of therapy.
- Associated Conditions
- Multiple Myeloma (MM), Refractory Multiple Myeloma, Relapsed Multiple Myeloma
Balancing Efficacy and Cost Sustainability in Modern CLL Treatment: Insights from Dr. Pierluigi Porcu
• Clinicians treating chronic lymphocytic leukemia (CLL) face growing challenges in balancing clinical efficacy with long-term cost sustainability, requiring a holistic approach to patient care.
• Dr. Pierluigi Porcu emphasizes that effective CLL management requires understanding disease risk, patient comorbidities, and practice environment constraints including payer considerations.
• Despite its importance, value-based care adoption remains insufficient in oncology, with challenges in defining and measuring value across patient outcomes, quality of life, and treatment costs.
DARZALEX Dominates Multiple Myeloma Market with $11.6 Billion in Global Sales
• DARZALEX (daratumumab), Janssen's CD38-targeting monoclonal antibody, has transformed multiple myeloma treatment across all lines of therapy, generating $11.6 billion in worldwide sales in 2024.
• The drug's success stems from its versatility in combination regimens, expanded approvals for both newly diagnosed and relapsed/refractory patients, and the introduction of DARZALEX FASPRO, a convenient subcutaneous formulation.
• Despite growing competition from emerging therapies like Sanofi's SARCLISA and novel BCMA-targeting agents, DARZALEX maintains market leadership through first-mover advantage and robust clinical efficacy data.
DARZALEX® Subcutaneous Regimen Receives CHMP Backing for Newly Diagnosed Multiple Myeloma Treatment
• Johnson & Johnson's DARZALEX® subcutaneous formulation combined with VRd receives positive CHMP recommendation for treating newly diagnosed multiple myeloma patients, regardless of transplant eligibility.
• The recommendation is supported by the Phase 3 CEPHEUS study, which evaluated the efficacy of daratumumab-VRd compared to VRd alone in 395 patients with newly diagnosed multiple myeloma.
• DARZALEX® has demonstrated significant impact in multiple myeloma treatment, having been used in over 618,000 patients worldwide and currently approved in eight indications.
Clinical Trial Diversity Crisis: Black Patients Severely Underrepresented in Multiple Myeloma Studies
• Recent phase 3 trials IMROZ and PERSEUS for multiple myeloma treatments showed alarming diversity gaps, with Black patients comprising only 0.9% and 1.3% of participants despite representing 20% of new myeloma cases.
• FDA study of 32,000 clinical trial participants reveals significant racial disparities, with non-Hispanic Whites overrepresented at 75% while Hispanic and Black populations remain underrepresented relative to US demographics.
• Real-world multiple myeloma patients show 44% worse progression-free survival compared to clinical trial participants, highlighting the consequences of non-representative trial populations.
Evorpacept Shows Promise in HER2-Positive Gastric Cancer: Updated ASPEN-06 Data
• ALX Oncology's ASPEN-06 Phase 2 trial evaluates evorpacept, a CD47-blocker, in HER2-positive advanced gastric cancer patients who have been previously treated.
• Updated data from the ASPEN-06 trial were presented at the 2025 ASCO Gastrointestinal Cancers Symposium (ASCO GI).
• The virtual event hosted by ALX Oncology on January 23, reviewed the ASPEN-06 data, focusing on evorpacept's potential in immuno-oncology.
• The ASPEN-06 trial is a phase 2/3 study of evorpacept in patients with HER2-overexpressing gastric/gastroesophageal cancer.
FDA Lifts Clinical Hold on Opella's Cialis OTC Switch Trial
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• This decision marks Cialis as the first PDE-5 inhibitor to reach this milestone, paving the way for a new self-care solution for erectile dysfunction.
• The AUT will evaluate Cialis's use under real-world conditions, ensuring consumers can self-diagnose and treat appropriately without medical supervision.
• Opella is completing clinical and regulatory activities to initiate the pivotal AUT, with study information available on clinicaltrials.gov.
Sanofi Halts Amcenestrant Development After Disappointing First-Line Breast Cancer Trial
• Sanofi discontinues the development of amcenestrant, an oral selective estrogen receptor degrader (SERD), after it failed in the AMEERA-5 phase 3 trial.
• The AMEERA-5 trial compared amcenestrant plus palbociclib to letrozole plus palbociclib as a first-line treatment for HR-positive/HER2-negative advanced breast cancer.
• This failure raises concerns about the potential of SERDs in the first-line treatment of breast cancer, impacting other developers in the field.
• Sanofi will discontinue all amcenestrant studies, including the AMEERA-6 trial in early-stage HR+ breast cancer patients.
J&J Boosts Neuroscience Pipeline with ITCI Acquisition, FDA Approves Spravato Monotherapy for TRD
• Johnson & Johnson (J&J) is set to acquire Intra-Cellular Therapies (ITCI) for $14.6 billion, adding Caplyta for bipolar disorder and schizophrenia to its neuroscience pipeline.
• The FDA has approved J&J's Spravato as a monotherapy for treatment-resistant depression (TRD), based on positive data from the phase IV TRD4005 study.
• AstraZeneca and Daiichi Sankyo's datopotamab deruxtecan (Dato-DXd) received FDA priority review for a lung cancer indication and was approved for previously treated breast cancer.
Sarclisa (Isatuximab) Shows Promise in Multiple Myeloma Treatment: China Approval and Subcutaneous Formulation Advances
• China's NMPA has approved Sarclisa (isatuximab) in combination with pomalidomide and dexamethasone for relapsed/refractory multiple myeloma, marking a significant milestone for Sanofi.
• A Phase 3 IRAKLIA trial demonstrated that subcutaneous isatuximab, delivered via an on-body system, achieved non-inferior objective response rates compared to intravenous administration.
• Regulatory submissions for subcutaneous isatuximab are planned in the US and EU in the first half of 2025, potentially offering a more convenient administration option for patients.
FDA Approvals in 2024: Advancing Treatment Paradigms in Solid Tumors and Hematologic Malignancies
• The FDA granted over 65 approvals in 2024, significantly impacting treatment paradigms across various cancers, including breast, gynecologic, skin, and genitourinary malignancies.
• Several tumor-agnostic approvals, such as fam-trastuzumab deruxtecan-nxki (Enhertu) for HER2-positive solid tumors and repotrectinib (Augtyro) for NTRK fusion-positive tumors, marked advancements in precision medicine.
• Immunotherapies like nivolumab (Opdivo) and pembrolizumab (Keytruda) received multiple approvals, including combinations with chemotherapy for urothelial and endometrial carcinomas, improving patient outcomes.
• Targeted therapies like vorasidenib (Voranigo) for low-grade glioma and selpercatinib (Retevmo) for RET-mutated thyroid cancers addressed unmet needs and demonstrated high efficacy and tolerability.
Duvakitug Shows Promise in Phase 2b Trial for Ulcerative Colitis and Crohn's Disease
• Teva and Sanofi's duvakitug met primary endpoints in a Phase 2b trial for ulcerative colitis (UC) and Crohn's disease (CD).
• In UC patients, 47.8% achieved clinical remission with a high dose of duvakitug, compared to 20.45% on placebo.
• In CD patients, 47.8% achieved endoscopic response with a high dose, compared to 13% on placebo, demonstrating potential as a new treatment option.
• The RELIEVE UCCD study's findings support advancing duvakitug to Phase 3 development, with plans to initiate in H2 2025.
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ASH 2024: Updates on Daratumumab, Selinexor, and Asciminib Highlighted
• Long-term follow-up data from the phase 3 AQUILA study will explore daratumumab monotherapy's efficacy in delaying progression in high-risk smoldering multiple myeloma.
• Updated results from the phase 1b/2 STOMP trial will present 96-week data on selinexor plus pomalidomide and dexamethasone in multiple myeloma.
• The ASH meeting will feature a 96-week data update from the phase 3 ASC4FIRST trial, assessing asciminib as a first-line treatment for CML-CP.
Daratumumab Plus VRd Improves Outcomes in Transplant-Ineligible Multiple Myeloma Patients
• The phase 3 CEPHEUS trial demonstrated that adding daratumumab to VRd significantly improved outcomes for transplant-ineligible newly diagnosed multiple myeloma patients.
• The quadruplet regimen achieved a 60.9% minimal residual disease (MRD) negativity rate compared to 39.4% with VRd alone, demonstrating a significant increase in treatment depth.
• Progression-free survival was also significantly improved with the daratumumab regimen, showing a 43% reduction in the risk of disease progression or death.
• These results suggest that daratumumab plus VRd could become a new standard of care for transplant-ineligible multiple myeloma patients, offering improved disease control.
Isatuximab Combinations Show Promise in Newly Diagnosed Multiple Myeloma
• Isatuximab plus VRd significantly reduced disease progression or death risk by 40.4% in transplant-ineligible newly diagnosed multiple myeloma patients.
• The FDA approved isatuximab-irfc with VRd for transplant-ineligible multiple myeloma, based on the IMROZ trial data.
• Isatuximab-RVd induction therapy improved progression-free survival in transplant-eligible newly diagnosed multiple myeloma patients, GMMG-HD7 trial showed.
• The addition of isatuximab to RVd led to higher rates of minimal residual disease negativity, indicating deeper responses.
Sanofi's Sarclisa Recommended for EU Approval in Newly Diagnosed Multiple Myeloma
• The EMA's CHMP has recommended Sanofi's Sarclisa in combination with Velcade, Revlimid, and dexamethasone (VRd) for newly diagnosed multiple myeloma patients ineligible for autologous stem cell transplant.
• The recommendation is based on the Phase III IMROZ trial, which demonstrated improved progression-free survival with the Sarclisa-VRd combination compared to VRd alone.
• Sarclisa targets the CD38 protein on multiple myeloma cells, inducing anti-tumor activity and has already been approved in over 50 countries for relapsed or refractory multiple myeloma.
• The EC approval will provide access to a potentially transformative new combination regimen, marking a significant step forward in multiple myeloma treatment.
European Commission Approves Sanofi's Sarclisa with VRd for Newly Diagnosed Multiple Myeloma
• The European Commission has approved Sarclisa (isatuximab-irfc) in combination with bortezomib, lenalidomide, and dexamethasone (VRd) for treating newly diagnosed multiple myeloma (NDMM) in adults not eligible for autologous stem cell transplant (ASCT).
• This approval marks Sarclisa as the first anti-CD38 therapy in the EU combined with VRd for transplant-ineligible NDMM patients, expanding its use beyond relapsed/refractory settings.
• The decision is based on the Phase 3 IMROZ study, which demonstrated a significant improvement in progression-free survival (PFS) with the Sarclisa-VRd combination compared to VRd alone.
• Sanofi continues to develop Sarclisa with ongoing Phase 2 and 3 trials, including exploring a subcutaneous delivery system to enhance patient comfort and convenience.
Sarclisa Approved in EU for Transplant-Ineligible Newly Diagnosed Multiple Myeloma
• The EU has approved Sarclisa, combined with bortezomib, lenalidomide, and dexamethasone (VRd), for newly diagnosed multiple myeloma patients ineligible for stem cell transplant.
• The approval is based on the IMROZ phase 3 trial, which demonstrated significantly improved progression-free survival compared to VRd alone.
• Sarclisa is now the first anti-CD38 therapy available in the EU for use with VRd in this specific patient population, addressing a critical unmet need.
• Regulatory submissions for Sarclisa in NDMM are under review in Japan and China, potentially expanding its availability globally.
Sarclisa Approved for First-Line Multiple Myeloma Treatment in Transplant-Ineligible Patients
• The FDA has approved Sarclisa (isatuximab) in combination with bortezomib, lenalidomide, and dexamethasone (VRd) as a first-line treatment for transplant-ineligible multiple myeloma.
• The approval was based on the IMROZ phase 3 trial, which showed a 40% reduction in disease progression or death compared to VRd alone.
• Sarclisa is the first anti-CD38 therapy approved with VRd for this patient population, offering a new standard of care.
• The combination demonstrated high rates of complete response and minimal residual disease negativity, improving long-term outcomes.
Bispecific Antibodies Teclistamab and Talquetamab Show Promise in Multiple Myeloma Treatment
• Teclistamab and talquetamab, bispecific antibodies, demonstrate efficacy in relapsed/refractory multiple myeloma by reducing soluble BCMA levels in responding patients.
• A reduction in sBCMA levels correlates with the depth of treatment response, with complete or stringent complete responses showing nearly 100% sBCMA reduction.
• Baseline sBCMA levels correlate with tumor burden, suggesting sBCMA as a potential marker, and do not significantly affect teclistamab exposure, indicating maintained clinical activity.
• Clinical trials are underway to evaluate bispecific antibodies in earlier lines of therapy and maintenance settings, potentially transforming myeloma treatment.
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