FDA Approves First Subcutaneous Infliximab for Maintenance Therapy in UC and Crohn Disease

Credit: US Food and Drug Administration

The US Food and Drug Administration has approved infliximab-dyyb (ZYMFENTRA) for use in adult patients with moderately to severely active ulcerative colitis (UC) and Crohn disease (CD) following treatment with an infliximab product administered intravenously.

Announced on October 22, 2023 by Celltrion USA, infliximab-dyyb becomes the first and only FDA-approved subcutaneous formulation of infliximab approved for the maintenance treatment of adult patients with moderately to severely active UC and CD.

“As a healthcare professional dedicated to improving the lives of patients with IBD, I am excited to see further data that validate a convenient treatment option that could allow more patients in the US to have greater control of their disease management,” said Jean-Frederic Colombel, MD, of Icahn School of Medicine at Mount Sinai.¹

With the first approval of infliximab, marketed as Remicade, coming in August 1998, the agent would be the first of many from the TNF inhibitor class to receive approval and ascend into guidelines for a slew of inflammatory disease, including psoriatic arthritis and pediatric indications for inflammatory bowel diseases. The approval of infliximab-dyyb could represent the next historic step in this journey.

According to Celltrion USA, the approvals of infliximab-dyyb comes after the submission of a Biologics License Application in December 2022 and is based on data from the LIBERTY-UC and LIBERTY-CD studies.

LIBERTY-UC Study

LIBERTY-UC was a randomized, placebo-controlled phase 3 trial launched with the intent of comparing infliximab-dyyb against placebo therapy during maintenance therapy in patients with moderate to severe active UC who had previously underwent induction therapy with intravenous infliximab. A total of 438 patients underwent randomization in the trial.

Results of the study suggested those randomized to infliximab-dyyb experienced a significantly greater rate of clinical remission at week 54 than those randomized to placebo therapy (43.2% vs 20.8%; P <.0001). Results of the safety analysis suggested the observed safety profile was comparable between the placebo and infliximab-dyyb arms, with COVID-19, anemia, arthralgia, injection site reaction, increased alanine aminotransferase, and abdominal pain were the most common adverse events.

LIBERTY-CD Study

Similar to LIBERTY-UC, the LIBERTY-CD study was a randomized, placebo-controlled phase 3 trial launched with the intent of comparing infliximab-dyyb against placebo therapy during maintenance therapy, but in patients with moderate to severe active CD who had previously underwent induction therapy with intravenous infliximab. A total of 343 patients underwent randomized in the trial.

Results of the study suggested those randomized to infliximab-dyyb experienced a significantly greater rate of clinical remission at week 54 than those randomized to placebo therapy (62.3% vs 32.1%; P <.0001). Analysis of endoscopic response rates at week 54 suggested the response rates were greater in the inflximab-dyyb cohort than among those in the placebo cohort (51.1% vs 17.9%; P <.0001).¹

The safety analysis performed as part of the study indicatedthe observed safety profile was comparable between the placebo and infliximab-dyyb arms. The most common adverse events were COVID-19, upper respiratory tract infection, headache, injection site reaction, diarrhea, increased alanine aminotransferase, and increased blood creatine phosphokinase, neutropenia, hypertension, urinary tract infection, dizziness, and leukopenia.¹

“There remains an unmet need for patients who suffer from the day-to-day burden of living with moderately to severely active Crohn’s disease and ulcerative colitis,” said Thomas Nusbickel, chief commercial officer at Celltrion USA.¹ “The approval of ZYMFENTRA provides an innovative and effective treatment option that offers patients with IBD an alternative administration option providing control of how and where they receive their treatment, reinforcing our commitment to providing high-quality and affordable treatment options that deliver substantial value to patients and our healthcare system.”

References:

1. Celltrion USA. Celltrion USA Announces U.S. FDA Approval of ZYMFENTRATM (infliximab-dyyb), the First and Only Subcutaneous infliximab, for the Treatment of People With Inflammatory Bowel Disease. Celltrion USA. October 22, 2023. Accessed October 23, 2023. https://www.celltrionusa.com/board/newslist/7.
2. Melsheimer R, Geldhof A, Apaolaza I, Schaible T. Remicade® (infliximab): 20 years of contributions to science and medicine. Biologics. 2019;13:139-178. Published 2019 Jul 30. doi:10.2147/BTT.S207246