FDA Approves Infliximab-dyyb for Inflammatory Bowel Disease

The FDA has approved infliximab-dyyb (Zymfentra; Celltrion USA) for the maintenance treatment of adults with moderately to severely active ulcerative colitis (UC) and Crohn disease (CD) after intravenous (IV) administration of an infliximab product. Zymfentra stops the action of tumor necrosis factor-alpha (TNF-alpha), which can be overproduced as a response to certain diseases and may prompt the immune system to attack healthy parts of the body.

“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, in a press release.

“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,” he continued.

The approval was based on pivotal phase 3 trial data demonstrating its efficacy and safety as maintenance therapy in patients with moderately to severely active UC (LIBERTY-UC) and CD (LIBERTY-CD).

LIBERTY-UC was a randomized, placebo-controlled, double-blind, phase 3 study comparing SC Zymfentra to placebo in terms of efficacy and safety during maintenance therapy in patients with moderately to severely active UC following induction therapy of the IV formulation of infliximab.

The investigators randomized 438 patients with response after induction at week 10. The data showed that the rate of clinical remission at week 54 was significantly higher in the Zymfentra cohort at 43.2% compared to 20.8% in the placebo cohort (P<0.0001).

Safety findings during the maintenance phase was generally comparable between the treatment and placebo cohorts, according to the study. The commonly reported adverse events (AEs) were COVID-19, anemia, arthralgia, injection site reaction, increased alanine aminotransferase, and abdominal pain.

LIBERTY-CD was a randomized, placebo-controlled, double-blind, phase 3 study that compared the efficacy and safety of SC Zymfentra to placebo during maintenance therapy in patients with moderately to severely active CD following induction therapy with IV infliximab.

Investigators randomized 343 patients with response after induction at week 10. At week 54, the clinical remission rate was 62.3% in the Zymfentra cohort compared with 32.1% in the placebo cohort (P <0.0001). Further, the endoscopic response rate at week 54 was also higher in the treatment cohort vs the placebo cohort, at 51.1% and 17.9%, respectively (P <0.0001).

Similar to the LIBERTY-UC trial, the safety profile during the maintenance phase was generally comparable between both trial arms. The most common AEs were COVID-19, upper respiratory tract infection, headache, injection site reaction, diarrhea, increased alanine aminotransferase, increased blood creatine phosphokinase, neutropenia, hypertension, urinary tract infection, dizziness, and leukopenia.

The results of both trials demonstrated the superiority of Zymfentra in the primary endpoints of clinical remission (UC and CD) and endoscopic response (CD) vs placebo as maintenance therapy following induction therapy of IV infliximab in those with UC and CD over the 54-week study period.

“As a health care 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 U.S. to have greater control of their disease management,” said Dr. Jean-Frederic Colombel of Icahn School of Medicine at Mount Sinai, in a press release.

Reference

Celltrion USA Announces U.S. FDA Approval of ZYMFENTRA™ (infliximab-dyyb), the First and Only Subcutaneous infliximab, for the Treatment of People With Inflammatory Bowel Disease. Celltrion USA. News release. October 23, 2023. https://www.celltrionhealthcare.com/board/en_newslist/109