Myositis: Muscle Inflammation | Inflammatory Myopathy

FDA Approves Genmab's Epkinly To Treat Adults With Relapsed Or Refractory Follicular Lymphoma After Two Or More Lines Of Systemic Therapy

Approval of Epkinly was based on results from the Phase I/II EPCORE trial in patients with relapsed or refractory follicular lymphoma who have already completed two or more lines of systemic therapy.

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The FDA has approved Genmab A/S and AbbVie's Epkinly (epcoritamab-bysp) for the treatment of adults with relapsed or refractory (R/R) follicular lymphoma (FL) after two or more lines of systemic therapy. According to the company, the approval marks the first time that a subcutaneous T-cell engaging bispecific antibody has been approved in the United States for this indication. The approval of Epkinly was based on encouraging results from the Phase I/II EPCORE clinical trial, which showed an overall response rate (ORR) of 82% in patients administered Epkinly.1

"Patients with relapsed or refractory follicular lymphoma face significant treatment challenges, especially in third-line settings where there is currently no clear standard of care treatment," said Jeff Sharman, MD, disease chair, hematology research, Sarah Cannon Research Institute at Willamette Valley Cancer Institute, Eugene, Oregon, in a press release. "This approval and the durable responses observed in the follicular lymphoma cohort of the EPCORE NHL-1 clinical trial, which reflected a real-world patient population, including patients with difficult-to-treat follicular lymphoma, demonstrate the potential of Epkinly for patients who face limited therapeutic options post-relapse."

EPCORE NHL-1 is an open-label, multi-center, safety and preliminary efficacy trial that consisted of dose escalation, expansion, and optimization portions, and it included 127 patients. Additionally, the trial aimed to evaluate subcutaneous Epkinly in patients with R/R B-cell non-Hodgkin's lymphoma, including FL. In the expansion part of the study, the primary endpoint was ORR assessed by an Independent Review Committee, with secondary endpoints including duration of response (DoR), complete response rate (CRR), duration of CRR, progression-free survival, and time to response as determined by the Lugano criteria. The primary endpoint of the optimization part was the rate of ≥ Grade 2 CRS events and all grade CRS events from first dose of Epkinly through seven days after the second dose.

In addition to the ORR findings, investigators observed a CRR of 60%, which included 67% of patients achieving minimal residual disease negativity. After a median follow-up of 14.8 months, the DoR was not reached. Overall, more than half of the patients responded to the treatment in some form.

Treatment-emergent adverse events (AEs) that were most common in the FL cohort were injection site reaction, cytokine release syndrome (CRS), COVID-19, fatigue, upper respiratory tract infection, musculoskeletal pain, rash, diarrhea, fever, cough, and headache. Those who were treated with Epinkly as part of the recommended three-step dosage schedule experienced low grade CRS.

Genmab warns that use of Epinkly can cause a number of serious AEs, including CRS and neurologic problems that could eventually lead to death. Additionally, it can cause infections and low blood cell counts.1

"With this approval, patients whose follicular lymphoma has relapsed or is refractory to at least two or more lines of systemic therapy, now have the option to be treated with Epkinly, which has demonstrated durable responses without mandatory hospitalization using a three step-up dosage regimen in this patient population in clinical trials," said Jan van de Winkel, PhD, CEO, Genmab, in the press release. "In just over a year, Epkinly has received a second indication in the US, making it the first and only bispecific antibody approved to treat patients with diffuse large B-cell lymphoma and follicular lymphoma after two or more lines of systemic therapy. The approved indications, along with the ongoing clinical development program, underscore the potential of [Epkinly] to become a core therapy across B-cell malignancies."

Reference

1. EPKINLY® (epcoritamab-bysp) Approved by U.S. FDA for Patients with Relapsed or Refractory (R/R) Follicular Lymphoma (FL). Genmab. June 27, 2024. Accessed June 27, 2024. Https://ir.Genmab.Com/news-releases/news-release-details/epkinlyr-epcoritamab-bysp-approved-us-fda-patients-relapsed-or

Epkinly Approved For Relapsed Or Refractory Follicular Lymphoma

The Food and Drug Administration (FDA) has granted accelerated approval to Epkinly® (epcoritamab-bysp) for the treatment of adults with relapsed or refractory (R/R) follicular lymphoma (FL) after 2 or more lines of systemic therapy. 

The approval was based on data from the open-label, multi-cohort, single-arm phase 1/2 EPCORE NHL-1 trial (ClinicalTrials.Gov Identifier: NCT03625037), which evaluated the efficacy and safety of epcoritamab, a bispecific CD20-directed CD3 T-cell engager, in 127 patients with R/R FL after at least 2 lines of systemic therapy. The primary endpoint was overall response rate (ORR).

Results showed an ORR of 82% (95% CI, 74.1-88.2); 60% of patients achieved complete response and 22% achieved partial response. After an estimated median follow-up of 14.8 months, the median duration of response (DOR; secondary endpoint) was not reached (NR) (95% CI, 13.7-NR). The 12-month Kaplan-Meier estimate for DOR was 68.4% (95% CI, 57.6-77.0).

"The FDA approval of Epkinly offers a new treatment option for relapsed or refractory follicular lymphoma, particularly following failure of other therapies," said Mariana Cota Stirner, MD, PhD, vice president, therapeutic area head for hematology, AbbVie. "Epkinly treatment has shown deep and durable responses for many patients. Subcutaneous dosing offers convenience, and Epkinly can be given to patients without mandatory hospitalization using a 3-step-up dosing regimen."

The most common adverse reactions reported during the trial were injection site reactions, cytokine release syndrome (CRS), COVID-19, fatigue, upper respiratory tract infection, musculoskeletal pain, rash, diarrhea, fever, cough, and headache. 

The prescribing information for Epkinly includes a Boxed Warning regarding the risk of serious or life-threatening CRS and immune effector cell-associated neurotoxicity syndrome. Among the 86 patients who were treated with the 3-step up dosage schedule for CRS mitigation, no grade 3 CRS was observed.

Epkinly is administered as a subcutaneous injection. The Epkinly 4mg/0.8mL is supplied as a single-dose vial that must be diluted prior to use. The Epkinly 48mg/0.8mL vial is supplied as a ready-to-use solution that does not need dilution prior to administration.

Epkinly is also indicated for the treatment of adults with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), not otherwise specified, including DLBCL arising from indolent lymphoma, and high grade B-cell lymphoma after 2 or more lines of systemic therapy.

Odronextamab Recommended For EU Approval By The CHMP To Treat Relapsed/Refractory Follicular Lymphoma And Diffuse Large B-cell Lymphoma

Regeneron Pharmaceuticals, Inc.

Recommendation based on data from the Phase 1 and pivotal Phase 2 trials demonstrating robust and durable response rates in both relapsed/refractory follicular lymphoma and diffuse large B-cell lymphoma

TARRYTOWN, N.Y., June 28, 2024 (GLOBE NEWSWIRE) -- Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) today announced that the European Medicines Agency's (EMA) Committee for Medicinal Products for Human Use (CHMP) has adopted a positive opinion recommending conditional marketing authorization of odronextamab to treat adults with relapsed/refractory (R/R) follicular lymphoma (FL) or R/R diffuse large B-cell lymphoma (DLBCL), after two or more lines of systemic therapy. The European Commission is expected to announce a final decision in the coming months.

FL and DLBCL are the two most common subtypes of B-cell non-Hodgkin lymphoma (B-NHL). While FL is a slow-growing subtype, it is an incurable disease, and most patients will relapse after initial treatment. DLBCL is an aggressive subtype, with up to 50% of high-risk patients experiencing progression after first-line treatment (e.G., relapsing or refractory to treatment). It is estimated that approximately 120,000 FL cases and 163,000 DLBCL cases are diagnosed annually worldwide. In Europe, it is estimated that approximately 15,000 FL cases and 31,000 DLBCL cases are diagnosed each year.

The positive CHMP opinion is supported by results from the Phase 1 ELM-1 and pivotal Phase 2 ELM-2 trials, which demonstrated robust, durable response rates and an acceptable safety profile of odronextamab in adults with R/R FL or R/R DLBCL. In a pooled safety population, the most common serious adverse reactions were cytokine release syndrome, pneumonia, COVID-19 and pyrexia.

The EMA previously granted odronextamab Orphan Designation for both FL and DLBCL. Odronextamab is currently under clinical development and has not been approved by any regulatory authority.

Regeneron continues to evaluate the use of odronextamab as a monotherapy and in combination across earlier lines of therapy in challenging-to-treat lymphomas. This includes the registrational ELM-1 and ELM-2 studies, the Phase 3 OLYMPIA development program, which is one of the largest clinical programs in lymphoma evaluating odronextamab in earlier lines of therapy and additional B-NHLs, as well as early-stage trials with chemotherapy-free combinations.

About the Odronextamab Clinical Trial ProgramOdronextamab is an investigational CD20xCD3 bispecific antibody designed to bridge CD20 on cancer cells with CD3-expressing T cells to facilitate local T-cell activation and cancer-cell killing.

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ELM-1 is an ongoing, open-label, multicenter Phase 1 trial to investigate the safety and tolerability of odronextamab in patients with CD20+ B-cell malignancies previously treated with CD20-directed antibody therapy, including a cohort of patients who had progressed after CAR-T therapy.

ELM-2 is an ongoing, open-label, multicenter Phase 2 trial investigating odronextamab across five independent disease-specific cohorts, including DLBCL, FL, mantle cell lymphoma, marginal zone lymphoma and other subtypes of B-NHL. The primary endpoint is objective response rate according to the Lugano Classification as assessed by independent review committee, and secondary endpoints include complete response, progression-free survival, overall survival and duration of response.

In addition to the Phase 3 OLYMPIA development program, Regeneron is investigating odronextamab in combination with a costimulatory bispecific antibody, REGN5837 (CD22xCD28), and Regeneron's PD-1 inhibitor cemiplimab for R/R aggressive B-NHL through the ATHENA-1 and CLIO-1 studies, respectively. For more information, visit the Regeneron clinical trials website, or contact clinicaltrials@regeneron.Com or +1 844-734-6643.

About Regeneron in HematologyAt Regeneron, we're applying more than three decades of biology expertise with our proprietary VelociSuite® technologies to develop medicines for patients with diverse blood cancers and rare blood disorders.

Our blood cancer research is focused on bispecific antibodies that are being investigated both as monotherapies and in combination with each other and emerging therapeutic modalities. Together, they provide us with unique combinatorial flexibility to develop customized and potentially synergistic cancer treatments.

Our research and collaborations to develop potential treatments for rare blood disorders include explorations in antibody medicine, gene editing and gene-knockout technologies, and investigational RNA approaches focused on depleting abnormal proteins or blocking disease-causing cellular signaling.

About RegeneronRegeneron (NASDAQ: REGN) is a leading biotechnology company that invents, develops and commercializes life-transforming medicines for people with serious diseases. Founded and led by physician-scientists, our unique ability to repeatedly and consistently translate science into medicine has led to numerous approved treatments and product candidates in development, most of which were homegrown in our laboratories. Our medicines and pipeline are designed to help patients with eye diseases, allergic and inflammatory diseases, cancer, cardiovascular and metabolic diseases, neurological diseases, hematologic conditions, infectious diseases, and rare diseases.

Regeneron pushes the boundaries of scientific discovery and accelerates drug development using our proprietary technologies, such as VelociSuite®, which produces optimized fully human antibodies and new classes of bispecific antibodies. We are shaping the next frontier of medicine with data-powered insights from the Regeneron Genetics Center® and pioneering genetic medicine platforms, enabling us to identify innovative targets and complementary approaches to potentially treat or cure diseases.

For more information, please visit www.Regeneron.Com or follow Regeneron on LinkedIn, Instagram, Facebook or X.

Forward-Looking Statements and Use of Digital MediaThis press release includes forward-looking statements that involve risks and uncertainties relating to future events and the future performance of Regeneron Pharmaceuticals, Inc. ("Regeneron" or the "Company"), and actual events or results may differ materially from these forward-looking statements. Words such as "anticipate," "expect," "intend," "plan," "believe," "seek," "estimate," variations of such words, and similar expressions are intended to identify such forward-looking statements, although not all forward-looking statements contain these identifying words. These statements concern, and these risks and uncertainties include, among others, the nature, timing, and possible success and therapeutic applications of products marketed or otherwise commercialized by Regeneron and/or its collaborators or licensees (collectively, "Regeneron's Products") and product candidates being developed by Regeneron and/or its collaborators or licensees (collectively, "Regeneron's Product Candidates") and research and clinical programs now underway or planned, including without limitation odronextamab; the impact of the opinion adopted by the European Medicines Agency's Committee for Medicinal Products for Human Use discussed in this press release on the potential conditional marketing authorization by the European Commission of odronextamab to treat adults with relapsed/refractory ("R/R") follicular lymphoma ("FL") or R/R diffuse large B-cell lymphoma ("DLBCL") after two or more lines of systemic therapy; the likelihood, timing, and scope of possible regulatory approval and commercial launch of Regeneron's Product Candidates and new indications for Regeneron's Products, such as odronextamab for the treatment of R/R FL or R/R DLBCL as discussed in this press release as well as odronextamab in combination with REGN5837 (CD22xCD28 costimulatory bispecific antibody) or cemiplimab (PD-1 inhibitor) as referenced in this press release; uncertainty of the utilization, market acceptance, and commercial success of Regeneron's Products and Regeneron's Product Candidates and the impact of studies (whether conducted by Regeneron or others and whether mandated or voluntary), including the studies discussed or referenced in this press release, on any of the foregoing; the ability of Regeneron's collaborators, licensees, suppliers, or other third parties (as applicable) to perform manufacturing, filling, finishing, packaging, labeling, distribution, and other steps related to Regeneron's Products and Regeneron's Product Candidates; the ability of Regeneron to manage supply chains for multiple products and product candidates; safety issues resulting from the administration of Regeneron's Products and Regeneron's Product Candidates (such as odronextamab) in patients, including serious complications or side effects in connection with the use of Regeneron's Products and Regeneron's Product Candidates in clinical trials; determinations by regulatory and administrative governmental authorities which may delay or restrict Regeneron's ability to continue to develop or commercialize Regeneron's Products and Regeneron's Product Candidates; ongoing regulatory obligations and oversight impacting Regeneron's Products, research and clinical programs, and business, including those relating to patient privacy; the availability and extent of reimbursement of Regeneron's Products from third-party payers, including private payer healthcare and insurance programs, health maintenance organizations, pharmacy benefit management companies, and government programs such as Medicare and Medicaid; coverage and reimbursement determinations by such payers and new policies and procedures adopted by such payers; competing drugs and product candidates that may be superior to, or more cost effective than, Regeneron's Products and Regeneron's Product Candidates; the extent to which the results from the research and development programs conducted by Regeneron and/or its collaborators or licensees may be replicated in other studies and/or lead to advancement of product candidates to clinical trials, therapeutic applications, or regulatory approval; unanticipated expenses; the costs of developing, producing, and selling products; the ability of Regeneron to meet any of its financial projections or guidance and changes to the assumptions underlying those projections or guidance; the potential for any license, collaboration, or supply agreement, including Regeneron's agreements with Sanofi and Bayer (or their respective affiliated companies, as applicable) to be cancelled or terminated; the impact of public health outbreaks, epidemics, or pandemics (such as the COVID-19 pandemic) on Regeneron's business; and risks associated with intellectual property of other parties and pending or future litigation relating thereto (including without limitation the patent litigation and other related proceedings relating to EYLEA®(aflibercept) Injection), other litigation and other proceedings and government investigations relating to the Company and/or its operations (including the pending civil proceedings initiated or joined by the U.S. Department of Justice and the U.S. Attorney's Office for the District of Massachusetts), the ultimate outcome of any such proceedings and investigations, and the impact any of the foregoing may have on Regeneron's business, prospects, operating results, and financial condition. 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