Davy James

The FDA has issued a second complete response letter (CRL) to Regeneron’s odronextamab based on issues with a third-party manufacturing site, Catalent Indiana LLC, the company announced in its Q2 earnings report.

FDA Cites Third-Party Site Issues at Catalent Indiana in CRL and Regulatory Delay

Regeneron’s Biologics License Application (BLA) is seeking the approval of odronextamab for the treatment of relapsed/refractory (R/R) follicular lymphoma (FL) and for R/R diffuse large B-cell lymphoma (DLBCL) following two or more prior lines of systemic therapy.

Regeneron also stated that it anticipates regulatory approvals to be delayed for a pending application for Eylea HD (aflibercept) injection 8 mg. The application, which was 

, seeks to expand use of the treatment for patients with macular edema following retinal vein occlusion to permit monthly dosing across all currently approved indications.

 The application was assigned PDUFA target action date of August 19, 2025.

Odronextamab’s Path to Approval Complicated by Evolving Phase III Trial Timelines

These delays are associated with issues raised during an FDA general site inspection at the Catalent Indiana LLC filler site, which was recently acquired by Novo Nordisk A/S. The inspection was completed in mid-July and was not specific to Eylea HD or odronextamab, according to Regeneron.

“Novo has been in communication with the FDA and expects to submit its response next week,” Regeneron stated in a press release. “Based on the Company's review of the observations and Novo's proposed response to the FDA, along with the progress the Company has made with alternate third-party fillers, the Company anticipates an expeditious resolution of the filling issues for Eylea HD.”

The first CRL issued to the BLA for odronextamab in March 2024 was based on the enrollment status of the confirmatory trials, but the FDA did not cite approvability issues related to the drug’s efficacy, safety, trial design, labeling, or manufacturing, according to Regeneron.

The FDA previously granted Priority Review to the BLA for odronextamab based on findings from the Phase 1 ELM-1 trial (NCT02290951) and the pivotal Phase II ELM-2 trial (NCT03888105).

“Regeneron has been actively enrolling patients in multiple Phase III trials for odronextamab as part of the OLYMPIA program—one of the largest clinical programs in lymphoma,” the company stated in a March 2024 press release. “As the OLYMPIA program is intended to change the treatment paradigm of several B-cell non-Hodgkin lymphoma subtypes—including in earlier lines of therapy—in agreeing to the program, the FDA required that the trials include both dose-finding and confirmatory portions. Enrollment in the dose-finding portion has begun, but the CRLs indicate that the confirmatory portions of these trials should be underway and that the timelines to completion be agreed prior to resubmission.”

Regeneron Posts Strong Q2 Earnings with Growth from Dupixent and Eylea HD US Sales

Despite these regulatory delays, Regeneron noted positive momentum across its lines of business. The company’s Q2 revenue increased 4% to $3.68 billion compared to the same period last year. This was powered by an increase in global net sales for Dupixent (dupilumab), which increased 22% to $4.34 billion. US net sales for Eylea HDincreased 29% to $393 million; however, total Eylea HD and Eylea US net sales dropped 25% to $1.15 billion.

"Regeneron had a strong quarter, marked by significant growth in US sales of Eylea HD and global sales of Dupixent and Libtayo along with multiple regulatory approvals," Leonard S. Schleifer, MD, PhD, board co-chair, president and CEO of Regeneron, said in the release. "We have made significant progress in our oncology portfolio, including FDA approval for Lynozyfic for relapsed or refractory multiple myeloma, exciting emerging data from the lead-in cohorts of our pivotal programs in myeloma and lymphoma, as well as positive pivotal data supporting a potential upcoming FDA approval for Libtayo in adjuvant CSCC. 

"Dupixent continues to be the world-leading treatment for diseases driven by type 2 inflammation, adding recent FDA approvals for bullous pemphigoid and chronic spontaneous urticaria, the seventh and eighth distinct indications for this important medicine. We are confident in the near- and long-term potential of our diverse pipeline and look forward to additional data and regulatory milestones later this year."

1. Regeneron Reports Second Quarter 2025 Financial and Operating Results. News release. Regeneron. August 1, 2025. Accessed August 1, 2025. 

https://www.globenewswire.com/news-release/2025/08/01/3125690/0/en/Regeneron-Reports-Second-Quarter-2025-Financial-and-Operating-Results.html

2. EYLEA HD® (aflibercept) Injection 8 mg sBLA Accepted for FDA Priority Review for Both the Treatment of Macular Edema Following Retinal Vein Occlusion (RVO) and for Monthly Dosing in Approved Indications. Regeneron. April 17, 2025. Accessed August 1, 2025. 

https://investor.regeneron.com/news-releases/news-release-details/eylea-hdr-aflibercept-injection-8-mg-sbla-accepted-fda-priority

3. Regeneron Provides Update On Biologics License Application For Odronextamab. Regeneron. News release. March 25, 2024. Accessed August 1, 2025. 

https://investor.regeneron.com/news-releases/news-release-details/regeneron-provides-update-biologics-license-application

4. Odronextamab BLA for treatment of relapsed/refractory follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL) accepted for FDA priority review. News release. Regeneron Pharmaceuticals. September 29, 2023. Accessed August 1, 2025. 

https://investor.regeneron.com/news-releases/news-release-details/odronextamab-bla-treatment-relapsedrefractory-follicular

Articles

Regeneron faces regulatory delays for odronextamab due to issues at a third-party manufacturing site, Catalent Indiana LLC. The FDA's second complete response letter (CRL) highlights these concerns, affecting the Biologics License Application (BLA) for treating relapsed/refractory follicular lymphoma and diffuse large B-cell lymphoma. Despite these setbacks, Regeneron reports strong Q2 earnings, driven by increased sales of Dupixent and Eylea HD. The company remains optimistic about its oncology portfolio and anticipates resolving the manufacturing issues swiftly, with ongoing Phase III trials for odronextamab under the OLYMPIA program.

Regeneron has received a second complete response letter from the FDA for odronextamab and anticipates delays for Eylea HD due to inspection findings at a Catalent manufacturing site, despite continued strong revenue growth and pipeline momentum.

FDA Delays Regeneron’s Odronextamab, Eylea HD Regulatory Decisions Over Catalent Site Issues

 on disparities in cancer incidence and mortality projects that by 2050, incidence rates and deaths will nearly triple in low-Human Development Index (HDI) countries compared to moderate increases in high-HDI countries. These findings highlight the need to strengthen global cancer prevention initiatives, emphasize early detection, and improve treatment efforts, according to the authors.

HDI combines indicators such as life expectancy, education, and gross national income per capita. The study noted a significant disruption of worldwide cancer prevention and care following the COVID-19 pandemic and made worse by ongoing global conflicts, a change in healthcare funding priorities, and increased cost-of-living. The study estimated that between 2020 and 2022, the global HDI experienced a substantial decrease across two straight years.

Investigators noted that the ongoing disruptions have had a disproportionate impact on cancer care across regions based on sociodemographic categories, causing disparities that can be analyzed via mortality to incidence ratio (MIR).

“Previous studies focused on the MIR were conducted using data collected prior to 2020 and data on selected cancer types, such as lung, liver, and gastric cancer,” the study authors wrote. “As already noted, global disruptions and shifts in health priorities underscore the need to continuously monitor cancer statistics globally to ensure delivery of equitable and optimal cancer prevention and care in uncertain times.”

Investigators conducted evidence-based decision-making for MIR on 36 types of cancer while analyzing disparities by geographic region, sex, and age from the most recent data from the Global Cancer Observatory (GLOBOCAN). Investigators also assessed cancer rates, prevalence, and projections for 2050. They gathered population-based data from 2022 for 185 countries and territories, with data extraction and analysis conducted in April 2024.

The study estimated a projected 35.3 million cancer cases worldwide by 2050, which represents a 76.6% increase from the estimated total of 20 million in 2022. For cancer deaths, investigators estimated an 89.7% increase from the 2022 estimate of 9.7 million, with 18.5 million cancer deaths projected by 2050.

“By 2050, cancer incidence in low-HDI countries is projected to increase 142.1% compared with 41.7% in very high–HDI countries, with estimated cancer deaths estimated to increase by 146.1% in low-HDI countries compared with 56.8% in very high–HDI countries,” the study authors wrote. “Strengthening the development and implementation of tobacco and alcohol control measures (including taxation, advertising bans, and smoke-free policies) and promoting access to and consumption of healthy diets rich in fruits, vegetables, and whole grains while limiting processed foods and saturated fats have been shown to reduce cancer risk. Expansion of community-based screening programs will be important for prevention, early detection, and reduction of cancer-related morbidity and mortality.”

The higher incidence and greater number of deaths among men in 2022 compared to women are projected to continue widening by nearly 16.0% in 2050. MIR in 2022 for all cancer types was 46.6%, with higher MIRs estimated for pancreatic cancer at 89.4%, in males at 51.7%, in individuals 75 years of age or older at 64.3%, and in low-HDI countries at 69.9% and the African region at 67.2%.

“On the basis of these findings, cancer cases and deaths are projected to nearly triple in low-income countries by 2050 compared to a moderate increase in high-income countries (142.1% vs 41.7% for cancer cases and 146.1% vs 56.8% for cancer deaths),” the study authors concluded. “Greater increases in cancer cases (15.8%) and deaths (8.0%) are projected among males compared with females. Strengthening health care access and quality, including universal health insurance coverage, and health care systems in the prevention, early diagnosis, management, and treatment of cancer will be paramount for improving clinical outcomes and slowing projected trends.”

1. Bizuayehu HM, Ahmed KY, Kibret GD, et al. Global Disparities of Cancer and Its Projected Burden in 2050. 

. 2024;7(11):e2443198. doi:10.1001/jamanetworkopen.2024.43198.

By 2050, study estimates that cancer incidence and mortality rates will nearly triple in low-Human Development Index countries, highlighting an urgent need for enhanced global cancer prevention, early detection, and treatment strategies to address growing disparities.

Global Study Warns Cancer Cases to Triple in Low-HDI Countries by 2050, Urging Enhanced Prevention, Care Initiatives

 to treat adults with active psoriatic arthritis (PsA), non-radiographic axial spondyloarthritis (nr-axSpA), and ankylosing spondylitis (AS). The regulatory action marks the first approval of a medication for these three conditions that selectively inhibits interleukin (IL)-17A and IL-17F, both of which are key cytokines that drive inflammatory processes.

“The approval of Bimzelx in the US across three new indications—active psoriatic arthritis, active [nr-axSpA] with objective signs of inflammation, and active ankylosing spondylitis—highlights the clinical benefit of dual inhibition of both IL-17A and IL-17F for patients, and provides an opportunity for more people living with chronic inflammatory diseases to achieve meaningful outcomes,” said Emmanuel Caeymaex, executive vice president, head of Patient Impact and chief commercial officer, UCB, said in a press release. “In [PsA] and across the spectrum of axSpA, clinical study results and real-world experience outside the US have highlighted that Bimzelx can help patients achieve high thresholds of clinical response that are rapid in onset and sustained up to two years.”

Bimzelx, a humanized monoclonal IgG1 antibody, was developed to selectively inhibit IL-17A and IL-17F. The drug was approved by the FDA in October 2023 for adults with moderate to severe plaque psoriasis who are eligible for systemic therapies or phototherapies. It was the first and only approved psoriasis treatment that selectively inhibits IL-17A and IL-17F inhibitor.

The newly approved indication of Bimzelx for adults with active PsA was based on findings from the Phase III BE OPTIMAL and BE COMPLETE trials. Investigators found that Bimzelx achieved the primary endpoint of American College of Rheumatology 50 (ACR50) response at week 16 compared with placebo, and also achieved all ranked secondary endpoints.

Efficacy findings were consistent across patients who are biologic-naïve and those who previously showed inadequate response to TNF inhibitor (TNFi) therapy. Investigators noted that the clinical responses achieved at week 16 were able to be sustained through week 52 in both BE OPTIMAL and BE COMPLETE, as well as an open-label extension trial as per the primary endpoint of ACR50, the ranked secondary endpoints of Psoriasis Area and Severity Index 90 (PASI90) minimal disease activity, and PASI100.

“Psoriatic arthritis can severely impact a person's quality of life. With joint pain and stiffness, daily activities can become burdensome. New treatment options are always a welcome addition, and they offer some renewed hope for relief from the symptoms and health impacts of PsA,” Leah M. Howard, JD, president and CEO of the National Psoriasis Foundation, said in a press release.

The approved indication for adults with active nr-axSpA with objective signs of inflammation, and active AS were based on results from the Phase III BE MOBILE 1 and BE MOBILE 2 studies. Across both analyses, Bimzelx achieved the primary endpoint of Assessment of SpondyloArthritis international Society 40 (ASAS40) response at week 16 vs. placebo, as well as all ranked secondary endpoints. Investigators noted consistent ASAS40 responses across treatment-naïve patients and who those had an inadequate response to TNFi-therapy. Further, clinical responses achieved at 16 weeks were able to be sustained across populations with nr-axSpA and AS through week 52 as assessed by ASAS40, ranked secondary endpoints, and other endpoints.

“In the Phase III clinical studies, patients treated with bimekizumab-bkzx saw improvements in signs and symptoms and key measures of disease activity at Week 16 which were sustained to one year and consistent across patients with non-radiographic axial spondyloarthritis and ankylosing spondylitis,” Atul Deodhar, MD, professor of Medicine and medical director of rheumatology clinics at the Division of Arthritis & Rheumatic Diseases, Oregon Health & Science University, Portland, Oregon, said in the release. “The US rheumatology community welcomes the approval of bimekizumab-bkzx for use across the entire spectrum of axial spondyloarthritis, especially given that there are few options approved currently to treat both non-radiographic axial spondyloarthritis and ankylosing spondylitis.”

1. UCB Announces U.S. FDA Approvals for BIMZELX® (bimekizumab-bkzx) for the Treatment of Psoriatic Arthritis, Non-radiographic Axial Spondyloarthritis, and Ankylosing Spondylitis. News release. UCB. September 23, 2024. Accessed September 23, 2024. 

https://www.ucb-usa.com/stories-media/UCB-U-S-News/detail/article/ucb-announces-us-fda-approvals-for-bimzelxr-bimekizumab-bkzx-for-the-treatment-of-psoriatic-arthritis-non-radiographic-axial-spondyloarthritis-and-ankylosing-spondylitis

2. BIMZELX Approved by the U.S. FDA for the Treatment of Adults with Moderate-to-Severe Plaque Psoriasis. UCB. News release. October 18, 2023. Accessed September 23, 2024. 

https://www.ucb-usa.com/stories-media/UCB-U-S-News/detail/article/bimzelx-approved-by-the-us-fda-for-the-treatment-of-adults-with-moderate-to-severe-plaque-psoriasis

Bimzelx is the first approved medication for active psoriatic arthritis, non-radiographic axial spondyloarthritis, and ankylosing spondylitis that selectively inhibits IL-17A and IL-17F, both of which are key cytokines that drive inflammatory processes.

FDA Approves Bimzelx for Psoriatic Arthritis, Non-Radiographic Axial Spondyloarthritis, and Ankylosing Spondylitis 

The FDA has approved Accord BioPharma's 420 mg strength Hercessi (trastuzumab-strf), a biosimilar to Herceptin, for the treatment of human epidermal growth factor receptor 2 (HER2)-overexpressing breast and gastric cancers.

 The regulatory action follows the April 2024 FDA approval of 150 mg strength Hercessi for the same indication.

The biosimilar now has approved indications for HER2-overexpressing breast cancer, HER2-overexpressing metastatic breast cancer (mBC), and HER2-overexpressing metastatic gastric or gastroesophageal junction adenocarcinoma.

"At Accord BioPharma, we are deeply committed to helping patients gain access to the medicines they need, and we will continue our efforts to help all stakeholders recognize the promise of biosimilars," Chrys Kokino, US president of Accord, said in a press release. "Although each cancer patient is unique, the cost of oncologic therapies often adds a significant burden on top of other existing challenges. We strive to respond to those needs with biosimilars like Hercessi."

The approval was based on findings from three studies that provided comprehensive analytical, preclinical, and clinical data, demonstrating equivalence between Hercessi and reference Herceptin in terms of efficacy, safety, and quality, according to Accord. These included a pair of Phase I comparative single-dose pharmacokinetic (PK) studies conducted in healthy participants—HLX02-HV01 and HLX02-HV02—as well as the supportive double-blind, randomized HLX02-BC01 Phase III trial. HLX02-BC01 analyzed efficacy and safety comparability data among patients with HER2-overexpressing mBC in combination with docetaxel. Investigators found that the PK comparability and clinical efficacy and safety data shown in the HLX02-HV02 and HLX02-BC01 trials adhere to the current biosimilar guidance from the FDA.

In terms of safety, the profile of Hercessi was consistent with the known safety profile of reference Herceptin. Data show no clinically meaningful differences between the biosimilar and reference product, which supports the biosimilarity between the two drugs, according to Accord.

Hercessi was originally developed by Shanghai Henlius Biotech, with exclusive rights to develop and commercialize the drug in the United States and Canada granted to Accord in 2021.

"The strength and success of our collaboration with Accord continues with the approval of the 420mg strength of Hercessi,” said Dr. Jason Zhu, executive director and CEO of Henlius in a press release. “This represents an important step in our journey to meet the needs of patients with innovative, high quality, and affordable therapeutics."

The impact of approved biosimilars on drug pricing has been significant. A study released last year by the University of Southern California’s Leonard D. Schaeffer Center for Health Policy & Economics and published in 

 compared trastuzumab to five biosimilar entrants. Investigators found that the reference trastuzumab began losing market share immediately after the biosimilar Kanjinti (trastuzumab-anns; Amgen) launched, and continues to lose market share to the other approved biosimilars.

“With multiple biosimilar competitors entering the US market quickly, trastuzumab is the best example to date of biosimilars fulfilling their promise to reduce biologic drug prices,” said Alice Chen, PhD, associate professor and vice dean for research at the Sol Price School of Public Policy at the University of Southern California, in a press release. “In just three years, the trastuzumab market displayed important hallmarks of competition: doctors could choose among six products; new entrants rapidly captured market share from the originator; and prices steadily declined on all six options. Prices of some versions declined by more than half, and the originator lost half of the market.”

1. Accord BioPharma, Inc. Announces U.S. Food & Drug Administration Approval of 420mg Strength of HERCESSI™ (trastuzumab-strf), a biosimilar to Herceptin® (trastuzumab), for the Treatment of Several Forms of HER2-Overexpressing Cancer. News release. Accord BioPharma. September 18, 2024. Accessed September 18, 2024. 

https://prnmedia.prnewswire.com/news-releases/accord-biopharma-inc-announces-us-food--drug-administration-approval-of-420mg-strength-of-hercessi-trastuzumab-strf-a-biosimilar-to-herceptin-trastuzumab-for-the-treatment-of-several-forms-of-her2-overexpressing-cance-302251163.html

2. Accord BioPharma, Inc. Announces U.S. Food & Drug Administration Approval of HERCESSI™ (trastuzumab-strf), a biosimilar to Herceptin® (trastuzumab) for the Treatment of Several Forms of HER2-Overexpressing Cancer. PR Newswire. April 29, 2024. Accessed September 18, 2024. 

https://www.prnewswire.com/news-releases/accord-biopharma-inc-announces-us-food--drug-administration-approval-of-hercessi-trastuzumab-strf-a-biosimilar-to-herceptin-trastuzumab-for-the-treatment-of-several-forms-of-her2-overexpressing-cancer-302129508.html

3. Accord BioPharma Announces U.S. FDA Acceptance of Biologics License Application for Proposed Biosimilar Trastuzumab HLX02. PR Newswire. April 5, 2023. Accessed September 18, 2024. 

https://www.prnewswire.com/news-releases/accord-biopharma-announces-us-fda-acceptance-of-biologics-license-application-for-proposed-biosimilar-trastuzumab-hlx02-301790459.html

4. Biosimilars drug market isn’t broken after all, USC Schaeffer study finds. News release. EurekAlert. June 6, 2023. Accessed September 18, 2024. 

https://www.eurekalert.org/news-releases/991617

Accord BioPharma's 420 mg strength Hercessi (trastuzumab-strf), a biosimilar to Herceptin, gains FDA approval to treat HER2-overexpressing breast cancer and gastric cancer.