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Endeavor Reports Positive Results from Trial of ENV-101 in Patients with IPF

May 20, 2024

Rare Daily Staff

Endeavor BioMedicines reported results from a completed phase 2a clinical trial that demonstrate the company’s lead investigational candidate, ENV-101, improved lung function and reversed key measures of lung fibrosis in patients with idiopathic pulmonary fibrosis over a 12-week period.

The results, which also showed that ENV-101 had an acceptable tolerability profile, were presented for the first time in a late-breaking oral session at the American Thoracic Society 2024 International Conference.

“There is a tremendous need for IPF treatments that do more than slow the inevitable decline of lung function,” said Toby Maher, professor of Medicine and director of Interstitial Lung Disease at Keck School of Medicine, University of Southern California, Los Angeles, who presented the data. “These preliminary signs of clinical and antifibrotic activity suggest that ENV-101 has the potential to change the trajectory of this otherwise relentless disease.”

Idiopathic Pulmonary Fibrosis (IPF) is a chronic, progressive lung disease that affects more than 100,000 adults in the United States. Although the exact cause of IPF is unknown, various environmental factors can lead to repeated injuries to lung cells that trigger abnormal wound-healing processes and life-threatening lung scarring. IPF has limited treatment options and a very poor prognosis: the average life expectancy is only three to five years after diagnosis.

Current standard-of-care therapies do not address the underlying cause of IPF. They slow the decline of lung function, but do not stop or reverse it, and they have tolerability issues that limit their long-term use in most patients. ENV-101 is designed to block a cellular wound-healing pathway known as hedgehog (Hh) that is abnormally activated in fibrotic lung diseases, such as IPF, and causes the continuous pathophysiologic buildup of scar tissue in the lungs.

The randomized, double-blind, placebo-controlled phase 2a clinical trial evaluated the safety and efficacy of ENV-101 vs. placebo in 41 patients with confirmed idiopathic pulmonary fibrosis. Patients at 16 sites in five countries were randomized 1:1 to receive 200 mg of ENV-101 or placebo once daily for 12 weeks. The primary endpoint for the trial was overall safety of ENV-101. Secondary endpoints included change from baseline to week 12 on lung function, measured by forced vital capacity (FVC) mL and percent predicted FVC (ppFVC), and patient reported outcomes based on the UCSD shortness-of-breath questionnaire. Key exploratory endpoints included mean change from baseline in total lung capacity (TLC) and change from baseline for percent quantitative interstitial lung disease (QILD), percent quantitative lung function (QLF) and percent quantitative ground glass (QGG), as measured by high-resolution computed tomography (HRCT).

Patients who received ENV-101 experienced a statistically significant improvement in lung function through the 12 weeks of the trial, with a 1.9 percent mean improvement in percent predicted forced vital capacity (ppFVC) from baseline as compared to a mean decline in ppFVC of 1.3 percent for patients in the placebo group.

Patients who received ENV-101 showed a statistically significant increase in total lung capacity (TLC) above baseline at 12 weeks with a 200 mL mean increase as compared to a mean decline of 56 mL for patients who received placebo. In ENV-101-treated patients, 80 percent experienced an increase in TLC while 70 percent of patients who received placebo showed a decrease in TLC.

Treatment with ENV-101 significantly decreased the absolute percent of quantitative interstitial lung disease (QILD) from baseline by 9.4 percent, as compared to an increase of 1.1 percent for patients who received placebo.

Treatment with ENV-101 decreased the absolute percent of quantitative lung fibrosis (QLF) by 2 percent from baseline, as compared to an increase of 0.87 percent in patients who received placebo.

Treatment with ENV-101 decreased the absolute percent of quantitative ground glass (QGG) by 4.6 percent from baseline, as compared to an increase of 0.29 percent in patients who received placebo.

There were no treatment-related serious adverse events, grade 3 or 4 adverse events, or clinically meaningful safety findings on laboratory analyses, vital signs, electrocardiograms, or physical examination reported for ENV-101-treated patients. The most common ENV-101-related adverse events were dysgeusia (alterations in taste; 57 percent), alopecia (52 percent) and muscle spasms (43 percent), which were all mild to moderate in severity.

Based on the ENV-101 Phase 2a trial results, Endeavor intends to initiate the phase 2 WHISTLE-PF trial. This trial is expected to include a global Phase 2b cohort in individuals with IPF and a parallel phase 2 cohort in individuals with progressive pulmonary fibrosis.

“These trial results suggest ENV-101 could have transformational clinical benefits for individuals with IPF, who are in need of therapies that change treatment expectations – from slowing disease progression to potentially reversing it,” said Paul Frohna, chief medical officer, Endeavor BioMedicines.

Photo: Paul Frohna, chief medical officer, Endeavor BioMedicines

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