Liminal issued a statement in early June 2021 explaining that the therapy’s clinical development for IPF had been halted. While the specific reasons behind this decision were not disclosed, the company stated that no dose-limiting adverse events or other potential safety concerns related to fezagepras had been observed.
The company’s decision came shortly after an announcement that Liminal would test fezagepras in a Phase 2 trial involving IPF patients in early 2022.
How does fezagepras work?
Fezagepras is a small molecule that is designed to slow lung tissue scarring, thickening, and inflammation, which are hallmarks of IPF. The therapy candidate does this by regulating the activity of several receptors that are known to be involved in metabolic, inflammatory, and fibrotic (scarring) processes.
Fezagepras in clinical trials
Studies in mouse models of pulmonary fibrosis showed that fezagepras was able to lower the levels of molecules that promoted tissue scarring, leading to significant easing of the disease.
Liminal completed a Phase 2 clinical trial (NCT02538536) of fezagepras in January 2017. The study involved 40 IPF patients, ages 40 and older, at six sites in Canada.
All received four 200-mg oral capsules of fezagepras daily for five months. One group took fezagepras by itself, while another was given the investigational therapy along with Esbriet (pirfenidone). Yet another group was given fezagepras in combination with Ofev (nintedanib). Both Esbriet and Ofev are approved oral treatments for IPF.
The patients receiving fezagepras alone, or in combination with Ofev, experienced few changes in their forced vital capacity (FVC) scores, which are a measure of lung function. However, those treated with fezagepras and Esbriet saw their FVC scores drop significantly over time. Of note, FVC is a lung function parameter that measures the amount of air a person can forcibly exhale from their lungs after a deep breath.
All of the treatment regimens were safe, the researchers said. The most common side effect was diarrhea. Additional analyses revealed that when given alongside Esbriet, fezagepras degraded faster, suggesting the existence of a potential drug interaction between the two therapies that lowered their effectiveness.
Liminal in December 2020 launched a Phase 1 trial (NCT04695041) in the U.K. that involves healthy volunteers. That trial is evaluating the safety, tolerability, and pharmacological properties of multiple increasing doses of fezagepras. The goal was to test doses that would be higher than those evaluated in previous studies, in order to define an optimal dosing schedule to be used in future trials of IPF and other disorders.
Interim pharmacological data from this study led the company to decide to halt fezagepras’ clinical development for IPF and hypertriglyceridemia, a condition in which triglycerides — the most abundant fatty molecules in the body — are excessively high.
The FDA granted fast track status to fezagepras in 2017. The investigational therapy also was named an orphan drug in the U.S. and Europe for the treatment of IPF. All of these designations are aimed at accelerating a medication’s development and regulatory review.
Liminal also conducted trials to evaluate the therapeutic potential of fezagepras for other conditions, including Alström syndrome (NCT03184584 and NCT02739217), cystic fibrosis (NCT02955888), and type 2 diabetes with metabolic syndrome (NCT02562573 and NCT03081598).
Last updated: June 7, 2021
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