Endeavor BioMedicines' ENV-101 Shows Improved Lung Function in Idiopathic Pulmonary Fibrosis

Endeavor BioMedicines, a biotechnology company in the clinical-stage, has revealed promising results from a Phase 2a clinical trial of its lead investigational drug, ENV-101, aimed at treating idiopathic pulmonary fibrosis (IPF). The findings, showcasing significant improvements in lung function and the reversal of key lung fibrosis measures, were presented at the American Thoracic Society 2024 International Conference.

ENV-101, a novel Hedgehog (Hh) signaling pathway inhibitor, has demonstrated statistically significant enhancements in lung capacity and function over a 12-week treatment period. This drug also exhibited an acceptable tolerability profile, bolstering its potential as the first disease-modifying treatment for IPF patients. According to Dr. Toby M. Maher, Professor of Medicine and Director of Interstitial Lung Disease at the Keck School of Medicine, University of Southern California, the need for treatments that do more than merely slow lung function decline is critical. The preliminary clinical and antifibrotic activity results of ENV-101 point to its potential to alter the course of this relentlessly progressive disease.

Typically, current standard-of-care therapies do not address the root cause of IPF. They only slow the progression of lung function decline without reversing it and often come with tolerability concerns that hinder long-term usage. ENV-101 aims to inhibit an overactive cellular wound-healing pathway known as Hedgehog, which is implicated in the development of lung fibrosis in diseases like IPF.

Key findings from the Phase 2a trial demonstrated that patients administered ENV-101 experienced an average improvement in percent predicted forced vital capacity (ppFVC) by 1.9% over 12 weeks, compared to a 1.3% decline in the placebo group. Additionally, total lung capacity (TLC) increased by an average of 200 mL in the ENV-101 group, whereas the placebo group saw a mean decline of 56 mL. Notably, 80% of patients treated with ENV-101 exhibited an increase in TLC.

High-resolution computed tomography (HRCT) scans revealed additional encouraging results. Treatment with ENV-101 significantly reduced the absolute percentage of quantitative interstitial lung disease (QILD) by 9.4%, in contrast to a 1.1% increase in the placebo group. Similarly, the drug decreased quantitative lung fibrosis (QLF) by 2% and quantitative ground glass (QGG) by 4.6%, compared to increases in the placebo group.

No serious adverse events or significant safety concerns were linked to ENV-101. Common, yet mild-to-moderate, side effects included dysgeusia (taste alterations), alopecia, and muscle spasms.

Dr. Paul A. Frohna, Chief Medical Officer of Endeavor BioMedicines, highlighted the potential transformational clinical benefits of ENV-101 for patients with IPF, emphasizing the need for therapies that can potentially reverse disease progression. Building on the promising Phase 2a trial results, Endeavor BioMedicines plans to launch the Phase 2 WHISTLE-PF trial, which will encompass both a global Phase 2b cohort for IPF and a parallel Phase 2 cohort for progressive pulmonary fibrosis (PPF).

The Phase 2a trial was a randomized, double-blind, placebo-controlled study evaluating the safety and efficacy of ENV-101 in 41 IPF patients across multiple international sites. Primary endpoints centered on safety, while secondary endpoints included changes in lung function and patient-reported outcomes.

Idiopathic pulmonary fibrosis is a chronic, progressive lung disease affecting over 100,000 adults in the United States, characterized by unknown causes and a poor prognosis. Current treatments offer limited options and generally poor life expectancy post-diagnosis.

ENV-101, by targeting the Hedgehog signaling pathway, aims to disrupt the aberrant wound-healing processes contributing to lung fibrosis. This could potentially reverse lung scarring and improve overall lung function and capacity in patients with both IPF and PPF.

Endeavor BioMedicines remains committed to advancing its investigational therapies, with ENV-101 at the forefront, to provide new hope and improve outcomes for patients suffering from these debilitating lung diseases.