RegulationFast Track (United States), Accelerated Approval (United States), Orphan Drug (United States), Orphan Drug (European Union), Conditional marketing approval (China), Special Review Project (China), Orphan Drug (Japan)

Structure/Sequence

Molecular FormulaC40H57N5O7

InChIKeyBLMPQMFVWMYDKT-NZTKNTHTSA-N

CAS Registry868540-17-4

Sequence Code 16182110

258

Clinical Trials associated with Carfilzomib

NCT06918990

/ Not yet recruitingPhase 2IIT

Targeting the B Cell Response to Treat Antibody-Mediated Rejection With Carfilzomib and Belatacept (CarBel)

The purpose of this study is to see:
1. If using these two drugs (carfilzomib and belatacept) together is safe
2. If the use of these two study drugs in addition to the usual immunosuppression for kidney transplant patients can improve your transplanted kidney function by lowering the antibodies you have against your transplanted kidney
3. If the study drugs effect the immune cells that were responding to your donor kidney. And, whether blood or urine tests can measure signs of inflammation and kidney cell injury
4. If using new computer techniques can help describe important changes seen on biopsy in your donated kidneys
The primary objective is to assess the efficacy of carfilzomib and belatacept therapy when added to current treatment with steroids and maintenance immunosuppression, compared to conventional treatment alone, to improve the clinical outcome of renal transplant patients with active and chronic - active ABMR occurring more than 6 months after renal transplantation or less than 6 months post-transplant with persistent refractory Antibody-Mediated Rejection (ABMR)

Start Date30 Jun 2025

Sponsor / Collaborator

National Institute of Allergy & Infectious Diseases

NCT06892522

/ Not yet recruitingPhase 1

A Phase 1/2, Open-Label, Platform Study to Evaluate Safety and Efficacy of Etentamig Monotherapy or Etentamig Combinations in Subjects With Multiple Myeloma

Multiple myeloma (MM) is a cancer of the blood's plasma cells. The cancer is typically found in the bones and bone marrow (the spongy tissue inside of the bones) and can cause bone pain, fractures, infections, weaker bones, and kidney failure. Treatments are available, but MM can come back (relapsed) or may not get better (refractory) with treatment. This is a study to determine the safety, efficacy, and pharmacokinetics of Etentamig in adult participants with MM.
Etentamig is an investigational drug being developed for the treatment of MM. This study is broken into 4 substudies and each substudy consists of a dose escalation phase and dose expansion phase. Participants will receive escalating doses of etentamig alone or in combination with daratumumab and lenalidomide (DR), carfilzomib and dexamethasone (Kd) or lenalidomide (R). This will be followed by etentamig at the dose levels established during the escalation phases alone or in combination with DR, Kd, R. The participants can also receive daratumumab, lenalidomide and dexamethasone (DRd), R, or daratumumab, carfilzomib, and dexamethasone (DKd) as a comparator in the dose expansion phases. Around 440 adult participants with MM will be enrolled at approximately 50 sites worldwide
In all substudies, participants will receive escalating doses of etentamig as Intravenous (IV) infusions, alone or in combination with DR, R or Kd, followed by IV infusions of etentamig at the dose levels established during the escalation phases alone or in combination with IV and oral DRd, DKd, or R. The study duration is approximately 130 months.
There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at a hospital or clinic. The effect of the treatment will be checked by medical assessments, blood tests, checking for side effects and questionnaires.

Start Date02 Jun 2025

Sponsor / Collaborator

AbbVie, Inc.

NCT06627751

/ RecruitingPhase 2IIT

Phase II Clinical Trial of Mezigdomide/Carfilzomib/Dexamethasone (MeziKD) in Patients With Relapsed or Refractory Multiple Myeloma (MM) With Extramedullary Disease (EMD)

This phase II trial studies how well mezigdomide/carfilzomib/dexamethasone (MeziKD) works in treating patients with multiple myeloma (MM) that has come back after a period of improvement (relapsed) or that does not respond to treatment (refractory) and have tumors from myeloma cells outside the bone marrow in the soft tissues or organs of the body (extramedullary disease [EMD]). Mezigdomide blocks important processes in myeloma cells and may lead to modulation of the immune system, including activation of T-lymphocytes, and downregulation of the activity of other proteins, some of which play key roles in the proliferation of certain cancer cell types. Carfilzomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Dexamethasone is a type of corticosteroid and is used to kill myeloma cells. It is used with other drugs to treat multiple myeloma. Giving MeziKD may kill more cancer cells in patients with relapsed/refractory multiple myeloma (RRMM) with EMD.

Start Date01 May 2025

Sponsor / Collaborator

Roswell Park Comprehensive Cancer Center

100 Clinical Results associated with Carfilzomib

100 Translational Medicine associated with Carfilzomib

100 Patents (Medical) associated with Carfilzomib

2,553

Literatures (Medical) associated with Carfilzomib

01 Jul 2025·BIOMEDICINE & PHARMACOTHERAPY

Population pharmacokinetics of cefazolin in neurosurgical antibiotic prophylaxis

Article

Author: Legros, Vincent ; Duflot, Thomas ; Marlier, Benoit ; Malinovsky, Jean-Marc ; Riffault, Maxime ; Feliu, Catherine ; Scala-Bertola, Julien ; Djerada, Zoubir ; Kleiber, Jean-Charles ; Rouget, David ; Konecki, Céline

In neurosurgery, cefazolin (CFZ) is typically recommended at a dose of 2-gram within 60 minutes prior to surgical incision. However, due to the reported poor cerebrospinal fluid (CSF) penetration of CFZ, we conducted a population pharmacokinetic study to assess the adequacy of a 2-gram CFZ dosing regimen against the most common pathogens found in neurosurgical patients. If necessary, alternative CFZ dosing strategies were identified to achieve effective CSF concentrations. Adult patients undergoing neurosurgery were considered for inclusion in a prospective, observational, single-center study. After intravenous administration of CFZ 2-gram, blood and CSF samples were collected to determine CFZ concentrations. Population pharmacokinetic modeling of CFZ was performed using a non-linear mixed-effects approach and different dosing regimens were evaluated pharmacodynamically via Monte Carlo simulations. A total of 147 plasma and 42 CSF samples from 23 patients were analyzed. The median CFZ concentrations in plasma and CSF were 140.5 and 7.8 mg/L, respectively. The final model selected was a two-compartment model with an additional CSF compartment without covariates. The standard 2 g CFZ dose was inadequate in most cases. In contrast, intermittent administration of 1 g every hour following an initial bolus of 4-5 g, or continuous infusion at a rate of 1.625 g/h after a 6 g bolus provided better target attainment. The standard 2 g CFZ dose for neurosurgical antibiotic prophylaxis should be reassessed. The alternative dosing regimens proposed in this study warrant evaluation in future clinical trials.

01 Jul 2025·Translational Oncology

Carfilzomib promotes Iodine-125 seed radiation-induced apoptosis, paraptosis, and ferroptosis in esophageal squamous cell carcinoma by aggravating endoplasmic reticulum stress

Article

Author: Sun, Bai ; Wang, Hao ; Hu, Wen-Wei ; Qiang, Wei-Guang ; Wang, Chao ; Shi, Hong-Bing ; Yuan, Ye ; Zha, Yin-Lin

Iodine-125 (¹²⁵I) seed brachytherapy has been applied to treat various malignant tumors such as esophageal cancer, however, radioresistance can reduce its efficacy. Endoplasmic reticulum stress (ERS) and subsequent unfolded protein response (UPR) is one of the core mechanisms of ¹²⁵I seed radiation-induced cell death, thus aggravating ERS has been considered a promising sensitization strategy. Herein, we show that combination therapy of an irreversible proteasome inhibitor carfilzomib (CFZ) and ¹²⁵I seed radiation displayed strong anti-tumor effect on esophageal squamous cell carcinoma (ESCC). Mechanistically, ERS and UPR regulated multiple cell death modalities induced by the combination therapy, including apoptosis, paraptosis, and ferroptosis. ¹²⁵I seed radiation induced reactive oxygen species (ROS) production, DNA damage, p53 activation, and apoptosis. CFZ promoted ROS production, and augmented ¹²⁵I seed radiation-induced apoptosis via the mitochondrial pathway, which was mediated by the UPR-C/EBP homologous protein (CHOP) pathway and was independent of the p53 pathway. CFZ enhanced ¹²⁵I seed radiation-induced intracellular Ca²⁺ overload, protein ubiquitination, ERS, and UPR, consequently promoting paraptosis. ¹²⁵I seed radiation induced accumulation of intracellular Fe²⁺ and lipid peroxides but upregulated the expression of ferroptosis inhibitors, SLC7A11 and glutathione peroxidase 4 (GPX4). The combination therapy promoted ferroptosis by enhancing the accumulation of intracellular Fe²⁺ and downregulating GPX4 expression. The mouse experiment demonstrated that CFZ can promote the efficacy of ¹²⁵I seed radiation with good tolerance. Our findings suggest that combination therapy of ¹²⁵I seed radiation and CFZ is associated with multiple cell death modalities and may serve as a promising therapeutic strategy for ESCC.

01 Jun 2025·Materials Today Bio

Enhanced anticancer effect of carfilzomib by codelivery of calcium peroxide nanoparticles targeting endoplasmic reticulum stress

Article

Author: Wu, Xuan ; Wang, Jianfang ; Chen, Xiuping ; Chen, Jian-Li ; Xia, Xinyue ; Zhu, Xiao-Ming ; Chen, Xu ; Yin, Dan

Encouraged by the clinical success of proteasome inhibitors treating hematological malignancy, continuous efforts are being made to improve their efficacy and expand their applications to solid tumor therapy. In this study, liposomes were used to encapsulate the proteasome inhibitor carfilzomib (CFZ) and calcium peroxide (CaO₂) nanoparticles for effective combination therapy targeting the interplay between calcium overload and oxidative stress. Low-dose CaO₂ synergistically enhances the anticancer effect of CFZ in the human glioblastoma U-87 MG cells. The reactive oxygen species (ROS) generation and glutathione depletion by low-dose CaO₂ complement CFZ-induced ubiquitinated protein accumulation further triggering endoplasmic reticulum (ER) stress leading to calcium overload and mitochondrial dysfunction. The liposome-based codelivery system is capable of transporting CFZ and CaO₂ simultaneously to the tumor, and results in a superior antitumor effect in U-87 MG tumor-bearing mice compared with monotherapy. Taken together, CaO₂ holds great potential to sensitize proteasome inhibitors in the treatment of solid tumors, and this work also presents a new combination therapy strategy targeting the crosstalk between proteasome inhibitors and oxidative stress for future cancer therapy.

239

News (Medical) associated with Carfilzomib

03 Jun 2025

·www.prnewswire.com

DARZALEX FASPRO® (daratumumab and hyaluronidase-fihj)-based regimen shows 95 percent progression-free survival at four years in transplant-eligible, newly diagnosed patients with multiple myeloma who achieved sustained MRD negativity

More than half of patients maintained minimal residual disease (MRD) negativity (10-5) with DARZALEX FASPRO® for 24 months or longer in the Phase 3 PERSEUS study Data from Phase 3 CEPHEUS study show 60 percent overall MRD negativity (10−5) and improved PFS with DARZALEX FASPRO® in transplant-ineligible newly diagnosed patients CHICAGO, June 3, 2025 /PRNewswire/ -- Johnson & Johnson (NYSE: JNJ) today announced data from two studies highlighting that a DARZALEX FASPRO® (daratumumab and hyaluronidase-fihj)-based quadruplet regimen demonstrated deep and sustained minimal residual disease (MRD) negativity rates, and improved long-term progression-free survival (PFS) in patients with newly diagnosed multiple myeloma (NDMM), regardless of transplant status.1,2,3 Findings were highlighted as oral presentations of an analysis of sustained MRD in transplant-eligible patients from the Phase 3 PERSEUS study (Abstract #7501) and a subgroup analysis of transplant-ineligible patients in the Phase 3 CEPHEUS study (Abstract #7516) at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting. New analysis from the Phase 3 PERSEUS study shows the addition of DARZALEX FASPRO® to bortezomib, lenalidomide and dexamethasone (D-VRd), followed by an investigational maintenance regimen of DARZALEX FASPRO® with lenalidomide (D-R), led to improved and deepened rates of overall and sustained MRD negativity (10-5), defined as no cancer cells detected within 100,000 bone marrow cells) for at least 24 months, compared to VRd induction and consolidation with R maintenance. More than half of patients who received the DARZALEX FASPRO®-based regimen achieved sustained MRD negativity for 24 or more months and more than two-thirds of patients achieved sustained MRD-negativity at 12-months, showing 95.3 percent PFS at 48-months (95 percent confidence interval [CI], 0.3-2.3)—reinforcing the ability of DARZALEX FASPRO® to delay disease progression or death.1 "The data show that D-VRd followed by an investigational D-R maintenance regimen is a highly effective treatment option for transplant-eligible patients with newly diagnosed multiple myeloma," said Philippe Moreau*, M.D., head of the Hematology Department, University Hospital Hôtel-Dieu, Nantes, France and presenting author. "The depth and durability of MRD negativity observed—paired with unprecedented progression-free survival at four years—underscore the long-term benefit the DARZALEX FASPRO-based regimen can offer patients early in their treatment journey." At a median follow-up of 47.5 months, 24-month sustained MRD negativity rates at the 10⁻⁵ sensitivity threshold were more than double with D-VRd followed by investigational D-R maintenance (55.8 percent), compared to VRd followed by R maintenance (22.6 percent) (odds ratio [OR]=4.36; 95 percent CI, 3.15-6.05; P<0.0001). Similarly, MRD negativity at 12 months was higher with D-VRd and D-R maintenance at 64.8 percent compared to VRd and R maintenance (29.7 percent) (OR=4.42, 95 percent CI, 3.22-6.08, P<0.0001).1 Additional data from Phase 3 CEPHEUS study explore the benefits of DARZALEX FASPRO® in transplant-ineligible patients across cytogenetic risk status The post-hoc analysis of the Phase 3 CEPHEUS study focused exclusively on transplant-ineligible patients, reinforcing that adding DARZALEX FASPRO® to VRd significantly deepens response and prolongs PFS compared to VRd alone, even in patients who are older and considered frail by the Myeloma Geriatric Assessment score. At a median follow-up of 58.7 months, patients receiving D-VRd achieved markedly higher overall MRD negativity rates at the 10⁻⁵ sensitivity threshold with 60.4 percent versus 39.3 percent with VRd (OR 2.37; 95 percent CI, 1.47–3.80; P=0.0004). Furthermore, treatment with D-VRd resulted in high MRD-negativity rates at the 10⁻⁶ threshold (no cancer cells detected within 1,000,000 bone marrow cells) with 45.8 percent compared to 26.9 percent with VRd (OR 2.28; 95 percent CI, 1.40–3.73; P=0.0010). These deeper responses translated into improved long-term outcomes, with 69 percent of patients remaining progression free at 54-months when treated with D-VRd versus 48.0 percent with VRd (hazard ratio [HR] 0.51; 95 percent CI, 0.35–0.74). Overall survival (OS) numerically favored D-VRd (HR 0.66; 95 percent CI, 0.42–1.03), with an even greater benefit observed after censoring for COVID-19-related deaths (HR 0.55; 95 percent CI, 0.34–0.90).2 Additional data presented at ASCO included a subgroup analysis of the CEPHEUS trial for both transplant-ineligible and deferred NDMM patients who were considered high-risk for cytogenetic abnormalities (Abstract #7529). At a median follow-up of 58.7 months, overall MRD negativity rate was improved for patients with standard risk in D-VRd versus VRd. Rates by treatment arm in patients at high risk were comparable.3 "Across multiple studies, the growing body of data on DARZALEX-based regimens indicates impressive, deep responses and meaningful progression-free survival in patients with newly diagnosed multiple myeloma, including high risk," Jordan Schecter, MD, Vice President, Disease Area Leader, Multiple Myeloma, Johnson & Johnson Innovative Medicine. "These consistent results across patient populations, regardless of transplant eligibility, reinforce the role of DARZALEX FASPRO as a cornerstone of frontline therapy." In the PERSEUS and CEPHEUS studies, the safety profiles were consistent with the known safety profile for DARZALEX FASPRO®. About the PERSEUS Study The PERSEUS study is being conducted in collaboration with the European Myeloma Network as the sponsor. PERSEUS is an ongoing, randomized, open-label, Phase 3 study comparing the efficacy and safety of D-VRd during induction and consolidation versus VRd during induction and consolidation in patients with NDMM eligible for ASCT. Following consolidation, patients received an investigational treatment regimen for maintenance that included DARZALEX FASPRO® in combination with lenalidomide or lenalidomide alone. The trial was not designed to isolate the effect of DARZALEX FASPRO® in the maintenance phase of treatment. The efficacy of DARZALEX FASPRO® in combination with lenalidomide for maintenance has not been established. The primary endpoint is PFS, and secondary endpoints include overall CR or better rate, and overall MRD-negativity (in patients with CR or better). The median age is 61.0 (range, 32-70) years for patients in the D-VRd arm and 59.0 (range, 31-70) years for patients in the VRd arm.2 The study is being conducted in 14 countries in Europe and Australia. About the CEPHEUS Study CEPHEUS (NCT03652064) is an ongoing, multicenter, randomized, open-label, Phase 3 study comparing the efficacy and safety of D-VRd versus VRd in patients with newly diagnosed multiple myeloma who are transplant-ineligible or for whom transplant is not intended as initial therapy. Primary endpoint is overall MRD negativity rate at 10-5 sensitivity threshold. Secondary endpoints include CR or better rates, PFS, sustained MRD negativity rates for ≥12 months, MRD-negative rate at one year, overall response rates, time to and duration of response, PFS on next line of therapy, overall survival and safety. The trial has enrolled 396 patients in 13 countries. About Multiple Myeloma Multiple myeloma (MM) is a blood cancer that affects a type of white blood cell called plasma cells, which are found in the bone marrow.4 In multiple myeloma, these malignant plasma cells proliferate and replace normal cells in the bone marrow.5 Multiple myeloma is the second most common blood cancer worldwide and remains an incurable disease.6 In 2024, it is estimated that more than 35,000 people will be diagnosed with multiple myeloma in the U.S. and more than 12,000 will die from the disease.7 People with multiple myeloma have a 5-year survival rate of 59.8 percent. While some people diagnosed with multiple myeloma initially have no symptoms, most patients are diagnosed due to symptoms that can include bone fracture or pain, low red blood cell counts, tiredness, high calcium levels, kidney problems or infections.8,9 About DARZALEX FASPRO ® and DARZALEX ® DARZALEX FASPRO® (daratumumab and hyaluronidase-fihj) received U.S. FDA approval in May 2020 and is approved for nine indications in MM, four of which are for frontline treatment in newly diagnosed patients who are transplant-eligible or ineligible.3,6 It is the only subcutaneous CD38-directed antibody approved to treat patients with MM. DARZALEX FASPRO® is co-formulated with recombinant human hyaluronidase PH20, Halozyme's ENHANZE® drug delivery technology. DARZALEX® (daratumumab) received U.S. FDA approval in November 2015 and is approved in eight indications, three of which are in the frontline setting, including newly diagnosed patients who are transplant-eligible and ineligible.9 DARZALEX® is the first CD38-directed antibody approved to treat MM.9 DARZALEX®-based regimens have been used in the treatment of more than 618,000 patients worldwide. In August 2012, Janssen Biotech, Inc. and Genmab A/S entered a worldwide agreement, which granted Janssen an exclusive license to develop, manufacture and commercialize daratumumab.  For more information, visit .  DARZALEX FASPRO ® INDICATIONS AND IMPORTANT SAFETY INFORMATION    INDICATIONS  DARZALEX FASPRO® (daratumumab and hyaluronidase-fihj) is indicated for the treatment of adult patients with MM:  In combination with bortezomib, lenalidomide, and dexamethasone for induction and consolidation in newly diagnosed patients who are eligible for autologous stem cell transplant In combination with bortezomib, melphalan, and prednisone in newly diagnosed patients who are ineligible for autologous stem cell transplant In combination with lenalidomide and dexamethasone in newly diagnosed patients who are ineligible for autologous stem cell transplant and in patients with relapsed or refractory MM who have received at least one prior therapy In combination with bortezomib, thalidomide, and dexamethasone in newly diagnosed patients who are eligible for autologous stem cell transplant In combination with pomalidomide and dexamethasone in patients who have received at least one prior line of therapy including lenalidomide and a proteasome inhibitor (PI) In combination with carfilzomib and dexamethasone in patients with relapsed or refractory MM who have received one to three prior lines of therapy In combination with bortezomib and dexamethasone in patients who have received at least one prior therapy As monotherapy in patients who have received at least three prior lines of therapy including a PI and an immunomodulatory agent or who are double refractory to a PI and an immunomodulatory agent IMPORTANT SAFETY INFORMATION   CONTRAINDICATIONS     DARZALEX FASPRO® is contraindicated in patients with a history of severe hypersensitivity to daratumumab, hyaluronidase, or any of the components of the formulation.     WARNINGS AND PRECAUTIONS     Hypersensitivity and Other Administration Reactions     Both systemic administration-related reactions, including severe or life-threatening reactions, and local injection-site reactions can occur with DARZALEX FASPRO®. Fatal reactions have been reported with daratumumab-containing products, including DARZALEX FASPRO®.    Systemic Reactions     In a pooled safety population of 1249 patients with MM (N=1056) or light chain (AL) amyloidosis (N=193) who received DARZALEX FASPRO® as monotherapy or in combination, 7 percent of patients experienced a systemic administration-related reaction (Grade 2: 3.2 percent, Grade 3: 0.7 percent, Grade 4: 0.1 percent). Systemic administration-related reactions occurred in 7 of patients with the first injection, 0.2 percent with the second injection, and cumulatively 1 percent with subsequent injections. The median time to onset was 2.9 hours (range: 5 minutes to 3.5 days). Of the 165 systemic administration-related reactions that occurred in 93 patients, 144 (87 percent) occurred on the day of DARZALEX FASPRO® administration. Delayed systemic administration-related reactions have occurred in 1 percent of the patients.  Severe reactions included hypoxia, dyspnea, hypertension, tachycardia, and ocular adverse reactions, including choroidal effusion, acute myopia, and acute angle closure glaucoma. Other signs and symptoms of systemic administration-related reactions may include respiratory symptoms, such as bronchospasm, nasal congestion, cough, throat irritation, allergic rhinitis, and wheezing, as well as anaphylactic reaction, pyrexia, chest pain, pruritus, chills, vomiting, nausea, hypotension, and blurred vision.     Pre-medicate patients with histamine-1 receptor antagonist, acetaminophen, and corticosteroids. Monitor patients for systemic administration-related reactions, especially following the first and second injections. For anaphylactic reaction or life-threatening (Grade 4) administration-related reactions, immediately and permanently discontinue DARZALEX FASPRO®. Consider administering corticosteroids and other medications after the administration of DARZALEX FASPRO® depending on dosing regimen and medical history to minimize the risk of delayed (defined as occurring the day after administration) systemic administration-related reactions.     Ocular adverse reactions, including acute myopia and narrowing of the anterior chamber angle due to ciliochoroidal effusions with potential for increased intraocular pressure or glaucoma, have occurred with daratumumab-containing products. If ocular symptoms occur, interrupt DARZALEX FASPRO® and seek immediate ophthalmologic evaluation prior to restarting DARZALEX FASPRO®.     Local Reactions     In this pooled safety population, injection-site reactions occurred in 7 percent of patients, including Grade 2 reactions in 0.8 percent. The most frequent (>1 percent) injection-site reaction was injection-site erythema. These local reactions occurred a median of 5 minutes (range: 0 minutes to 6.5 days) after starting administration of DARZALEX FASPRO®. Monitor for local reactions and consider symptomatic management.     Neutropenia     Daratumumab may increase neutropenia induced by background therapy. Monitor complete blood cell counts periodically during treatment according to manufacturer's prescribing information for background therapies. Monitor patients with neutropenia for signs of infection. Consider withholding DARZALEX FASPRO® until recovery of neutrophils. In lower body weight patients receiving DARZALEX FASPRO®, higher rates of Grade 3-4 neutropenia were observed.     Thrombocytopenia     Daratumumab may increase thrombocytopenia induced by background therapy. Monitor complete blood cell counts periodically during treatment according to manufacturer's prescribing information for background therapies. Consider withholding DARZALEX FASPRO® until recovery of platelets.     Embryo-Fetal Toxicity     Based on the mechanism of action, DARZALEX FASPRO® can cause fetal harm when administered to a pregnant woman. DARZALEX FASPRO® may cause depletion of fetal immune cells and decreased bone density. Advise pregnant women of the potential risk to a fetus. Advise females with reproductive potential to use effective contraception during treatment with DARZALEX FASPRO® and for 3 months after the last dose.     The combination of DARZALEX FASPRO® with lenalidomide, thalidomide, or pomalidomide is contraindicated in pregnant women because lenalidomide, thalidomide, and pomalidomide may cause birth defects and death of the unborn child. Refer to the lenalidomide, thalidomide, or pomalidomide prescribing information on use during pregnancy.     Interference With Serological Testing     Daratumumab binds to CD38 on red blood cells (RBCs) and results in a positive indirect antiglobulin test (indirect Coombs test). Daratumumab-mediated positive indirect antiglobulin test may persist for up to 6 months after the last daratumumab administration. Daratumumab bound to RBCs masks detection of antibodies to minor antigens in the patient's serum. The determination of a patient's ABO and Rh blood type are not impacted.     Notify blood transfusion centers of this interference with serological testing and inform blood banks that a patient has received DARZALEX FASPRO®. Type and screen patients prior to starting DARZALEX FASPRO®.     Interference With Determination of Complete Response     Daratumumab is a human immunoglobulin G (IgG) kappa monoclonal antibody that can be detected on both the serum protein electrophoresis (SPE) and immunofixation (IFE) assays used for the clinical monitoring of endogenous M-protein. This interference can impact the determination of complete response and of disease progression in some DARZALEX FASPRO®-treated patients with IgG kappa myeloma protein.     ADVERSE REACTIONS     In MM, the most common adverse reaction (≥20 percent) with DARZALEX FASPRO® monotherapy is upper respiratory tract infection. The most common adverse reactions with combination therapy (≥20 percent for any combination) include fatigue, nausea, diarrhea, dyspnea, insomnia, headache, pyrexia, cough, muscle spasms, back pain, vomiting, hypertension, upper respiratory tract infection, peripheral sensory neuropathy, constipation, pneumonia, and peripheral edema.     The most common hematology laboratory abnormalities (≥40 percent) with DARZALEX FASPRO® are decreased leukocytes, decreased lymphocytes, decreased neutrophils, decreased platelets, and decreased hemoglobin.     Please click here to see the full Prescribing Information for DARZALEX FASPRO ® .     DARZALEX ® INDICATIONS AND IMPORTANT SAFETY INFORMATION INDICATIONS   DARZALEX ® (daratumumab) is indicated for the treatment of adult patients with MM:   In combination with bortezomib, melphalan, and prednisone in newly diagnosed patients who are ineligible for autologous stem cell transplant In combination with lenalidomide and dexamethasone in newly diagnosed patients who are ineligible for autologous stem cell transplant and in patients with relapsed or refractory MM who have received at least one prior therapy In combination with bortezomib, thalidomide, and dexamethasone in newly diagnosed patients who are eligible for autologous stem cell transplant In combination with pomalidomide and dexamethasone in patients who have received at least one prior line of therapy including lenalidomide and a proteasome inhibitor In combination with carfilzomib and dexamethasone in patients with relapsed or refractory MM who have received one to three prior lines of therapy In combination with bortezomib and dexamethasone in patients who have received at least one prior therapy As monotherapy in patients who have received at least three prior lines of therapy including a proteasome inhibitor (PI) and an immunomodulatory agent or who are double-refractory to a PI and an immunomodulatory agent CONTRAINDICATIONS DARZALEX® is contraindicated in patients with a history of severe hypersensitivity (eg, anaphylactic reactions) to daratumumab or any of the components of the formulation.   WARNINGS AND PRECAUTIONS   Infusion-Related Reactions   DARZALEX® can cause severe and/or serious infusion-related reactions including anaphylactic reactions. These reactions can be life-threatening, and fatal outcomes have been reported. In clinical trials (monotherapy and combination: N=2066), infusion-related reactions occurred in 37 percent of patients with the Week 1 (16 mg/kg) infusion, 2 percent with the Week 2 infusion, and cumulatively 6 percent with subsequent infusions. Less than 1 percent of patients had a Grade 3/4 infusion-related reaction at Week 2 or subsequent infusions. The median time to onset was 1.5 hours (range: 0 to 73 hours). Nearly all reactions occurred during infusion or within 4 hours of completing DARZALEX®. Severe reactions have occurred, including bronchospasm, hypoxia, dyspnea, hypertension, tachycardia, headache, laryngeal edema, pulmonary edema, and ocular adverse reactions, including choroidal effusion, acute myopia, and acute angle closure glaucoma. Signs and symptoms may include respiratory symptoms, such as nasal congestion, cough, throat irritation, as well as chills, vomiting, and nausea. Less common signs and symptoms were wheezing, allergic rhinitis, pyrexia, chest discomfort, pruritus, hypotension and blurred vision. When DARZALEX® dosing was interrupted in the setting of ASCT (CASSIOPEIA) for a median of 3.75 months (range: 2.4 to 6.9 months), upon re-initiation of DARZALEX®, the incidence of infusion-related reactions was 11 percent for the first infusion following ASCT. Infusion-related reactions occurring at re-initiation of DARZALEX® following ASCT were consistent in terms of symptoms and severity (Grade 3 or 4: <1 percent) with those reported in previous studies at Week 2 or subsequent infusions. In EQUULEUS, patients receiving combination treatment (n=97) were administered the first 16 mg/kg dose at Week 1 split over two days, ie, 8 mg/kg on Day 1 and Day 2, respectively. The incidence of any grade infusion-related reactions was 42 percent, with 36 percent of patients experiencing infusion-related reactions on Day 1 of Week 1, 4 percent on Day 2 of Week 1, and 8 percent with subsequent infusions. Pre-medicate patients with antihistamines, antipyretics, and corticosteroids. Frequently monitor patients during the entire infusion. Interrupt DARZALEX® infusion for reactions of any severity and institute medical management as needed. Permanently discontinue DARZALEX® therapy if an anaphylactic reaction or life-threatening (Grade 4) reaction occurs and institute appropriate emergency care. For patients with Grade 1, 2, or 3 reactions, reduce the infusion rate when re-starting the infusion. To reduce the risk of delayed infusion-related reactions, administer oral corticosteroids to all patients following DARZALEX® infusions. Patients with a history of chronic obstructive pulmonary disease may require additional post-infusion medications to manage respiratory complications. Consider prescribing short- and long-acting bronchodilators and inhaled corticosteroids for patients with chronic obstructive pulmonary disease. Ocular adverse reactions, including acute myopia and narrowing of the anterior chamber angle due to ciliochoroidal effusions with potential for increased intraocular pressure or glaucoma, have occurred with DARZALEX® infusion. If ocular symptoms occur, interrupt DARZALEX® infusion and seek immediate ophthalmologic evaluation prior to restarting DARZALEX®. Interference With Serological Testing   Daratumumab binds to CD38 on red blood cells (RBCs) and results in a positive indirect antiglobulin test (indirect Coombs test). Daratumumab-mediated positive indirect antiglobulin test may persist for up to 6 months after the last daratumumab infusion. Daratumumab bound to RBCs masks detection of antibodies to minor antigens in the patient's serum. The determination of a patient's ABO and Rh blood type is not impacted. Notify blood transfusion centers of this interference with serological testing and inform blood banks that a patient has received DARZALEX®. Type and screen patients prior to starting DARZALEX®. Neutropenia and Thrombocytopenia   DARZALEX® may increase neutropenia and thrombocytopenia induced by background therapy. Monitor complete blood cell counts periodically during treatment according to manufacturer's prescribing information for background therapies. Monitor patients with neutropenia for signs of infection. Consider withholding DARZALEX® until recovery of neutrophils or for recovery of platelets. Interference With Determination of Complete Response   Daratumumab is a human immunoglobulin G (IgG) kappa monoclonal antibody that can be detected on both the serum protein electrophoresis (SPE) and immunofixation (IFE) assays used for the clinical monitoring of endogenous M-protein. This interference can impact the determination of complete response and of disease progression in some patients with IgG kappa myeloma protein. Embryo-Fetal Toxicity   Based on the mechanism of action, DARZALEX® can cause fetal harm when administered to a pregnant woman. DARZALEX® may cause depletion of fetal immune cells and decreased bone density. Advise pregnant women of the potential risk to a fetus. Advise females with reproductive potential to use effective contraception during treatment with DARZALEX® and for 3 months after the last dose. The combination of DARZALEX® with lenalidomide, pomalidomide, or thalidomide is contraindicated in pregnant women because lenalidomide, pomalidomide, and thalidomide may cause birth defects and death of the unborn child. Refer to the lenalidomide, pomalidomide, or thalidomide prescribing information on use during pregnancy. ADVERSE REACTIONS   The most frequently reported adverse reactions (incidence ≥20 percent) were: upper respiratory infection, neutropenia, infusion related reactions, thrombocytopenia, diarrhea, constipation, anemia, peripheral sensory neuropathy, fatigue, peripheral edema, nausea, cough, pyrexia, dyspnea, and asthenia. The most common hematologic laboratory abnormalities (≥40 percent) with DARZALEX® are: neutropenia, lymphopenia, thrombocytopenia, leukopenia, and anemia. Please click here to see the full Prescribing Information. About Johnson & Johnson At Johnson & Johnson, we believe health is everything. Our strength in healthcare innovation empowers us to build a world where complex diseases are prevented, treated, and cured, where treatments are smarter and less invasive, and solutions are personal. Through our expertise in Innovative Medicine and MedTech, we are uniquely positioned to innovate across the full spectrum of healthcare solutions today to deliver the breakthroughs of tomorrow, and profoundly impact health for humanity. Learn more at or at . Follow us at @JNJInnovMed. Janssen Research & Development, LLC and Janssen Biotech, Inc., and Janssen Global Services, LLC are Johnson & Johnson companies. Cautions Concerning Forward-Looking Statements This press release contains "forward-looking statements" as defined in the Private Securities Litigation Reform Act of 1995 regarding product development and the potential benefits and treatment impact of DARZALEX FASPRO®. The reader is cautioned not to rely on these forward-looking statements. These statements are based on current expectations of future events. If underlying assumptions prove inaccurate or known or unknown risks or uncertainties materialize, actual results could vary materially from the expectations and projections of Johnson & Johnson. Risks and uncertainties include, but are not limited to: challenges and uncertainties inherent in product research and development, including the uncertainty of clinical success and of obtaining regulatory approvals; uncertainty of commercial success; manufacturing difficulties and delays; competition, including technological advances, new products and patents attained by competitors; challenges to patents; product efficacy or safety concerns resulting in product recalls or regulatory action; changes in behavior and spending patterns of purchasers of health care products and services; changes to applicable laws and regulations, including global health care reforms; and trends toward health care cost containment. A further list and descriptions of these risks, uncertainties and other factors can be found in Johnson & Johnson's most recent Annual Report on Form 10-K, including in the sections captioned "Cautionary Note Regarding Forward-Looking Statements" and "Item 1A. Risk Factors," and in Johnson & Johnson's subsequent Quarterly Reports on Form 10-Q and other filings with the Securities and Exchange Commission. Copies of these filings are available online at , , or on request from Johnson & Johnson. Johnson & Johnson does not undertake to update any forward-looking statement as a result of new information or future events or developments. Source: Johnson & Johnson * Philippe Moreau, M.D., head of the Hematology Department, University Hospital Hôtel-Dieu, Nantes, France, has provided consulting, advisory, and speaking services to Johnson & Johnson; he has not been paid for any media work. SOURCE Johnson & Johnson WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Clinical ResultPhase 3License out/inASCODrug Approval

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

100 Deals associated with Carfilzomib

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KEGG	Wiki	ATC	Drug Bank
D08880	Carfilzomib	L01XX45	DB08889

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Multiple Myeloma	United States	Onyx Pharmaceuticals, Inc.	20 Jul 2012

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Refractory Multiple Myeloma	Phase 3	United States	Amgen, Inc.	08 May 2019
Refractory Multiple Myeloma	Phase 3	Japan	Amgen, Inc.	08 May 2019
Refractory Multiple Myeloma	Phase 3	Austria	Amgen, Inc.	08 May 2019
Refractory Multiple Myeloma	Phase 3	Bulgaria	Amgen, Inc.	08 May 2019
Refractory Multiple Myeloma	Phase 3	Czechia	Amgen, Inc.	08 May 2019
Refractory Multiple Myeloma	Phase 3	Finland	Amgen, Inc.	08 May 2019
Refractory Multiple Myeloma	Phase 3	France	Amgen, Inc.	08 May 2019
Refractory Multiple Myeloma	Phase 3	Germany	Amgen, Inc.	08 May 2019
Refractory Multiple Myeloma	Phase 3	Greece	Amgen, Inc.	08 May 2019
Refractory Multiple Myeloma	Phase 3	Lithuania	Amgen, Inc.	08 May 2019

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT01863550 (ENDURANCE, ASCO2025)	Phase 3	Multiple Myeloma del17p \| t(14;16) \| t(14;20) ... View more	1,087	VRd (Bortezomib, Lenalidomide, Dexamethasone)	ezckqekuex(mpxufhuvdl) = fnfjezjjqw nxthfsayxz (ewjxrlobhr )	Positive	30 May 2025
				KRd (Carfilzomib, Lenalidomide, Dexamethasone)	ezckqekuex(mpxufhuvdl) = fkrizvwhhs nxthfsayxz (ewjxrlobhr )
ASCO2025	Not Applicable	Refractory Multiple Myeloma	-	Carfilzomib	djflerdcse(lttzaiomky): aOR = 1.61 (95% CI, 1.48 - 1.77), P-Value = < 0.001 View more	Negative	30 May 2025
				No Carfilzomib
NCT04268498 (ADVANCE, ASCO2025)	Phase 2	Multiple Myeloma minimal residual disease (MRD) positive	306	DKRd (Daratumumab, Carfilzomib, Lenalidomide, Dexamethasone)	kkqdwlgbdv(vynykobzui): adjusted OR = 2.5 (95% CI, 1.5 - 4.2) View more	Positive	30 May 2025
				KRd (Carfilzomib, Lenalidomide, Dexamethasone)
NCT03104842 (GMMG-CONCEPT, ASCO2025)	Phase 2	Multiple Myeloma HR cytogenetic aberration (CA) (del(17p), t(4;14), t(14;16), ≥3 copies 1q21)	219	Isatuximab, carfilzomib, lenalidomide, and dexamethasone (Isa-KRd)	kzdxznqnzs(wzhkwtsyxl) = mOS has not been reached uexesxuiwk (sxehdtakbf ) View more	Positive	30 May 2025
NCT05199311 (phase 1/2 study, ASCO2025)	Phase 2	Multiple Myeloma	38	Carfilzomib, iberdomide, and dexamethasone (KID)	tlnrmsypsd(afmajbhaxh) = zsvxeopvro gfkcktzuax (sepaeyzhyb ) View more	Positive	30 May 2025
NCT02659293 (ATLAS, ASCO2025)	Phase 3	Multiple Myeloma Maintenance	81	Carfilzomib, lenalidomide, and dexamethasone (KRd)	vtabrnbhaf(odgdmmilop) = suhcgzdnqj zmofhmicyb (fdkrlipvku ) View more	Positive	30 May 2025
				Lenalidomide (R)	vtabrnbhaf(odgdmmilop) = mtjxbkiuis zmofhmicyb (fdkrlipvku ) View more
NCT04113018 (MRD-driven phase 2 study, Pubmed \| Blood Adv)	Phase 2	Multiple Myeloma next-generation sequencing-based MRD	39	Daratumumab, Carfilzomib, Lenalidomide, Dexamethasone	zpoqrormjy(knzzodvese) = zyzuagjumk xhrqaomyjq (jfpkegqtaf, 10^ - 5)	Positive	11 Feb 2025
NCT02101944 (Pubmed) Manual	Phase 1	Multiple Myeloma	13	Pelareorep + carfilzomib	anvdilamic(iwnoobjirj) = ykxuasskap jmfglnobmy (jhwqudlkau )	Positive	20 Jan 2025
ASH2024	Not Applicable	Refractory Multiple Myeloma	-	MeziVd	redeatthxq(igiikxhdor) = The most common grade 3/4 TEAEs were neutropenia (35.7%), thrombocytopenia (21.4%), and infections (17.9%) with MeziVd; and neutropenia (44.4%) and infections (33.3%) with MeziKd xbsimrxmjr (wtnfruonkc ) View more	-	09 Dec 2024
				MeziKd
NCT02332850 (ASH2024) Manual	Phase 2	Multiple Myeloma	50	IsatuximabCarfilzomibDexamethasone	banhgcstog(igwwxmsuhi) = bapqnlcbbl ipuhokoytd (gxjosigufz ) View more	Positive	07 Dec 2024

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