Lenalidomide

GSK's Blenrep application is set to be discussed at a meeting of the FDA's Oncologic Drugs Advisory Committee on Thursday. GSK has been enjoying regulatory momentum in recent months as it works to bring its antibody-drug conjugate (ADC) Blenrep back to markets around the globe. But a new FDA briefing document indicates the company may need to address some of the agency's lingering concerns in order to reintroduce the drug in the key U.S. market.In a document (PDF) posted ahead of the July 17 meeting of the Oncologic Drugs Advisory Committee (ODAC), FDA reviewers flagged "high rates of ocular toxicity" and "uncertainty regarding the proposed dosages" as key issues for Thursday's discussion.On the ocular toxicity issue, FDA reviewers said the majority of patients in GSK's pivotal DREAMM-7 and DREAMM-8 trials experienced Keratopathy and Visual Acuity (KVA) events. KVA events at any grade occurred in 92% and 93% of patients in the trials, respectively, while grade 3-4 events happened in 77% and 78% of patients in the studies. In addition, treatment with GSK's Blenrep was "associated with severe ocular toxicities, including corneal ulcers and clinically significant decline in visual acuity, including severe vision loss," the document reads. In a particularly noteworthy comment from the agency, the reviewers said the corneal toxicity seen with the ADC drug is a "unique risk to this product and is not seen with currently available therapies" for multiple myeloma."There is potential for ocular toxicity to have a substantial impact on patient functioning and quality of life," FDA staffers added. "These toxicity concerns, coupled with the high rates of dose modifications, raise concerns about whether the dosages evaluated in DREAMM-7 and DREAMM-8 have been adequately optimized."Eye toxicity has been a known concern for Blenrep and a major bear case for GSK’s 3 billion-pound ($4 billion) peak sales plan for the BCMA-targeted ADC. The British pharma has proposed a dose modification scheme, but the FDA apparently still has questions about that.   GSK is seeking FDA approval for Blenrep—in combination with Takeda's Velcade and dexamethaone—to treat adults with multiple myeloma who've received at least one prior line of therapy. In addition, the company is pursuing a nod for the drug in combination with Bristol Myers Squibb's Pomalyst and dexamethasone in patients who've tried at least one prior line of therapy, including BMS' Revlimid.Blenrep won its original U.S. approval back in 2020 as a monotherapy for patients with multiple myeloma who've tried at least four therapies. But after the drug fell short in a confirmatory trial, GSK pulled Blenrep from markets worldwide in 2022. Since then, the pivotal DREAMM studies have shown the ability of the Blenrep combinations to improve patients' progression-free survival—and overall survival in the case of DREAMM-7—compared with standard of care (SoC) regimens. "Two independent, randomized Phase 3 studies consistently demonstrated clinically meaningful benefits of Blenrep arms over SoC arms across all endpoints, including statistically significant improvement in overall survival from the DREAMM-7 study," GSK said in its own briefing document (PDF) ahead of the advisory committee meeting."Overall, the efficacy data demonstrate the promise of Blenrep as an effective therapy in the evolving MM treatment landscape," GSK concluded.ODAC is slated to discuss whether "appropriate dosages" of the drug have been identified in trials and vote on the benefit-risk profiles of the two proposed regimens, according to draft questions (PDF) posted by the agency. The FDA itself its expected to act on GSK's application by July 23. As part of GSK's effort to bring the drug back to markets around the globe, regulators in the U.K. signed off on Blenrep combinations back in April, leveraging results from the DREAMM studies. The following month, Europe's Committee for Medicinal Products for Human Use endorsed the Blenrep regimens for use in that region.Riding the comeback momentum, GSK has projected that the ADC can deliver peak sales of more than 3 billion pounds sterling (about $4 billion). In fact, Blenrep's return was one factor cited in the company's recent decision to raise its 2031 sales target to more than 40 billion pounds.

– Monjuvi® (tafasitamab-cxix) in combination with rituximab and lenalidomide is the first FDA-approved CD19- and CD20-targeted immunotherapy combination for adult patients with follicular lymphoma (FL) – Patients with relapsed or refractory FL achieved significantly improved progression-free survival with Monjuvi in combination with rituximab and lenalidomide in the Phase 3 registration trial – This milestone represents the second approved indication for Monjuvi in the United States WILMINGTON, DE, USA I June 18, 2025 I Incyte (Nasdaq:INCY) today announced that the U.S. Food and Drug Administration (FDA) has approved Monjuvi® (tafasitamab-cxix), a humanized Fc-modified cytolytic CD19-targeting monoclonal antibody, in combination with rituximab and lenalidomide for the treatment of adult patients with relapsed or refractory follicular lymphoma (FL). “Patients living with relapsed or refractory FL have been waiting for new options that improve progression-free survival without substantial increase in side effects. Based on the data from the inMIND trial of Monjuvi, today’s approval brings to this patient population the first CD-19 and CD20-targeted immunotherapy combination and a potential new treatment standard,” said Hervé Hoppenot, Chief Executive Officer, Incyte. “This second U.S. approval for Monjuvi reinforces our commitment to advancing innovation for the lymphoma community.” The Priority Review and FDA approval of the supplemental Biologics License Application (sBLA) for Monjuvi was based on data from the pivotal, randomized, double-blind, placebo-controlled Phase 3 inMIND trial evaluating the efficacy and safety of Monjuvi in combination with rituximab and lenalidomide in adult patients with relapsed or refractory FL. Data from the trial was featured in the Late-breaking Session (LBA-1) at the 2024 American Society of Hematology (ASH) Annual Meeting. 1 The study met its primary endpoint demonstrating a statistically significant and clinically meaningful improvement in progression-free survival (PFS) by investigator assessment, which demonstrated 27.5% (N=273) of patients with an event in the Monjuvi group vs. 47.6% (N=275) of patients with an event in the control arm. Patients receiving Monjuvi in combination with rituximab and lenalidomide achieved a median PFS by investigator assessment of 22.4 months (95% CI, 19.2-not evaluable [NE]) compared to 13.9 months (95% CI, 11.5-16.4) in the control arm (hazard ratio [HR]: 0.43 [95% CI, 0.32-0.58]; P<0.0001). The PFS assessed by an Independent Review Committee (IRC) was consistent with investigator-based results. Median PFS by IRC was not reached (95% CI, 19.3-NE) in the Monjuvi group versus 16.0 months (95% CI, 13.9-21.1) in the control arm (HR: 0.41 [95% CI, 0.29-0.56]. The PFS benefit was consistent across prespecified patient subgroups, including number of previous lines of therapy. The safety of Monjuvi in patients with FL was evaluated in 546 patients in the inMIND trial. Serious adverse reactions occurred in 33% of patients who received Monjuvi in combination with rituximab and lenalidomide, including serious infections in 24% of patients (including pneumonia and COVID-19 infection). Other serious adverse reactions in ≥ 2% of patients included renal insufficiency (3.3%), second primary malignancies (2.9%), and febrile neutropenia (2.6%). Fatal adverse reactions occurred in 1.5% of patients, including from COVID-19, sepsis, and adenocarcinoma. The most common adverse reactions (≥ 20%) in recipients of Monjuvi, excluding laboratory abnormalities, were respiratory tract infections (including COVID-19 infection and pneumonia), diarrhea, rash, fatigue, constipation, musculoskeletal pain, and cough. The most common Grade 3 or 4 laboratory abnormalities (≥ 20%) were decreased neutrophils and decreased lymphocytes. “Follicular lymphoma is generally an indolent yet chronic cancer that frequently recurs after treatment, making long-term disease control a critical objective,” said Christina Poh, M.D., Assistant Professor of Medicine at the University of Washington and Fred Hutchinson Cancer Center. “The FDA approval of Monjuvi in combination with rituximab and lenalidomide marks a significant advancement, offering a chemotherapy-free option that has demonstrated a meaningful reduction in the risk of disease progression across a broad patient population, including those with high-risk disease.” FL is the second most common type of non-Hodgkin lymphoma (NHL) and represents up to 30% of NHL cases. 2 While considered an indolent, slow-growing disease with prolonged survival, FL is challenging to treat due to its tendency for frequent relapse, need for multiple lines of therapy and potential transformation into large B-cell lymphoma. 2,3 “While the initial responses to FL treatment are often positive, recurrence can become increasingly difficult for patients to manage as they navigate emotions and the next treatment steps related to relapse,” said Mitchell Smith, M.D., Ph.D., Chief Medical Officer, Follicular Lymphoma Foundation. “We are pleased that the FDA has approved tafasitamab, part of a treatment combination offering a new option for patients living with this chronic disease.” In July 2020, Monjuvi in combination with lenalidomide received FDA approval for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) not otherwise specified, including DLBCL arising from low grade lymphoma, and who are not eligible for autologous stem cell transplant (ASCT). This indication was approved under accelerated approval by the U.S. FDA based on overall response rate (ORR). Continued approval of Monjuvi for this indication may be contingent on verification and description of clinical benefit in confirmatory trial(s). Tafasitamab is also being evaluated as a therapeutic option in an ongoing pivotal trial for first-line DLBCL. Incyte is committed to supporting patients and removing barriers to access medicines. Eligible patients in the U.S. who are prescribed Monjuvi have access to IncyteCARES (Connecting to Access, Reimbursement, Education and Support), a comprehensive program offering personalized patient support, including financial assistance and ongoing education and additional resources. More information about IncyteCARES is available by visiting www.incytecares.com or calling 1-855-452-5234, Monday through Friday, from 8 a.m. to 8 p.m. ET. About inMIND A global, double-blind, randomized, controlled Phase 3 study, inMIND (NCT04680052) evaluated the efficacy and safety of tafasitamab in combination with rituximab and lenalidomide compared with placebo in combination with rituximab and lenalidomide in patients with relapsed or refractory follicular lymphoma (FL) Grade 1 to 3a or relapsed or refractory nodal, splenic or extranodal marginal zone lymphoma (MZL). The study enrolled a total of 654 adults (age ≥18 years). The primary endpoint of the study is progression-free survival (PFS) by investigator assessment in the FL population, and the key secondary endpoints are PFS in the overall population as well as positron emission tomography complete response (PET-CR) and overall survival (OS) in the FL population. For more information about the study, please visit https://clinicaltrials.gov/study/NCT04680052 . About Monjuvi ® (tafasitamab-cxix) Monjuvi ® (tafasitamab-cxix) is a humanized Fc-modified cytolytic CD19-targeting monoclonal antibody. In 2010, MorphoSys licensed exclusive worldwide rights to develop and commercialize tafasitamab from Xencor, Inc. Tafasitamab incorporates an XmAb ® engineered Fc domain, which mediates B-cell lysis through apoptosis and immune effector mechanism including Antibody-Dependent Cell-Mediated Cytotoxicity (ADCC) and Antibody-Dependent Cellular Phagocytosis (ADCP). MorphoSys and Incyte entered into: (a) in January 2020, a collaboration and licensing agreement to develop and commercialize tafasitamab globally; and (b) in February 2024, an agreement whereby Incyte obtained exclusive rights to develop and commercialize tafasitamab globally. In the U.S., Monjuvi is approved by the U.S. Food and Drug Administration in combination with lenalidomide and rituximab for the treatment of adult patients with relapsed or refractory follicular lymphoma (FL). MONJUVI is not indicated and is not recommended for the treatment of patients with relapsed or refractory marginal zone lymphoma outside of controlled clinical trials. Additionally, Monjuvi received accelerated approval in the United States in combination with lenalidomide for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) not otherwise specified, including DLBCL arising from low grade lymphoma, and who are not eligible for autologous stem cell transplant (ASCT). In Europe, Minjuvi ® (tafasitamab) received conditional Marketing Authorization from the European Medicines Agency in combination with lenalidomide, followed by Minjuvi monotherapy, for the treatment of adult patients with relapsed or refractory DLBCL who are not eligible for ASCT. XmAb® is a registered trademark of Xencor, Inc. Monjuvi, Minjuvi, the Minjuvi and Monjuvi logos and the “triangle” design are registered trademarks of Incyte. Please see the full Prescribing Information including the Medication Guide for Monjuvi. About Incyte A global biopharmaceutical company on a mission to Solve On. , Incyte follows the science to find solutions for patients with unmet medical needs. Through the discovery, development and commercialization of proprietary therapeutics, Incyte has established a portfolio of first-in-class medicines for patients and a strong pipeline of products in Oncology and Inflammation & Autoimmunity. Headquartered in Wilmington, Delaware, Incyte has operations in North America, Europe and Asia. For additional information on Incyte, please visit Incyte.com or follow us on social media: LinkedIn , X , Instagram , Facebook , YouTube . SOURCE: Incyte