FDA Accepts Nintedanib sNDA for Pediatric Fibrosing Interstitial Lung Disease

Credit: Boehringer Ingelheim

The US Food and Drug Administration (FDA) accepted a supplemental New Drug Application (sNDA) for nintedanib (OFEV). According to the developing company Boehringer Ingelheim, the application aimed to investigate the potential use of nintedanib as a treatment option for children and adolescents between the ages of 6 and 17 years suffering from fibrosing interstitial lung disease (ILD).¹

Fibrosing ILD is a rare and severe condition, encompassing more than 200 disorders. Its prevalence in the pediatric population remains uncertain, with reported incidence rates ranging from 1.6 - 46 per million children.

Among pediatric ILD cases, pulmonary fibrosis is even rarer, and globally recognized prevalence estimates are unavailable. The company’s statement noted that the lack of data, coupled with the significant mortality and morbidity associated with pediatric ILD, underscores the pressing need for effective treatment options.

The sNDA was supported by the promising results from the InPedILD phase 3 trial which evaluated the dose-exposure and safety of nintedanib in combination with the standard of care among children and adolescents with clinically significant fibrosing ILD.

The InPedILD trial, one of the first randomized controlled clinical trials dedicated to childhood ILDs, followed a double-blind, randomized, and placebo-controlled design. It involved a 24-week assessment period and open-label treatment with nintedanib for a variable duration.

The primary endpoints of the trial were the dose exposure at week 2 of nintedanib treatment and the proportion of patients experiencing treatment-emergent adverse events at week 24.

Of the 87 patients screened for participation in the trial, 39 patients, consisting of 12 patients aged 6 to 11 years, and 27 patients aged 12 to 17 years, were randomized and treated. Among these, 26 patients received nintedanib, while 13 patients received placebo during the initial 24 weeks before transitioning to nintedanib.

The results of the InPedILD trial demonstrated that a weight-based dosing regimen of nintedanib yielded exposure levels similar to that of adults, and it was found to have a comparable safety profile in the pediatric population. Investigators reported that diarrhea emerged as the most common adverse event associated with nintedanib compared with placebo in the trial.

Boehringer Ingelheim's pursuit of the sNDA for nintedanib seeks to address an unmet medical need, as there are currently no approved treatments specifically indicated for children and adolescents with these conditions. If the application is approved by the FDA, nintedanib will become the first and only treatment option available for these patients, offering renewed hope and improved health outcomes for those affected, that statement read.

The complete findings of the InPedILD phase 3 trial were published in the European Respiratory Journal (ERJ) and were also presented at the European Respiratory Society (ERS) International Congress in September 2022.

"With a long and complicated journey to diagnosis and no approved therapies, childhood interstitial lung diseases can place a significant burden on patients and their families," Robin Deterding, MD, director of the Breathing Institute, Children's Hospital Colorado stated. "If approved, OFEV would be the first and only approved treatment for children and adolescents aged 6-17 years old with fibrosing interstitial lung disease, representing an important step forward for these patients."

References:

1. U.S. FDA accepts supplemental New Drug Application for OFEV® (nintedanib) for children and adolescents aged 6-17 years old with fibrosing interstitial lung disease. News Release. Boehringer Ingelheim. July 25, 2023. https://prnmedia.prnewswire.com/news-releases/us-fda-accepts-supplemental-new-drug-application-for-ofev-nintedanib-for-children-and-adolescents-aged-6-17-years-old-with-fibrosing-interstitial-lung-disease-301885030.html