Study: ENV-101 improves IPF lung function, reverses fibrosis

Endeavor BioMedicines plans to begin Phase 2 WHISTLE-PF study

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by Andrea Lobo |

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Endeavor BioMedicines’ ENV-101 improved lung function and reversed key signs of lung scarring in people with idiopathic pulmonary fibrosis (IPF), according to data from a completed Phase 2a trial.

The results, which also showed the treatment had an acceptable tolerability profile, were presented in a late-breaking oral presentation at the American Thoracic Society 2024 (ATS 2024) International Conference in San Diego.

Based on the results from the Phase 2a trial (NCT04968574), the company intends to start another Phase 2 trial of ENV-101 called WHISTLE-PF (NCT06422884), which is expected to include up to 320 adults with IPF and progressive pulmonary fibrosis (PPF).

“There is a tremendous need for IPF treatments that do more than slow the inevitable decline of lung function,” Toby M. Maher, MD, PhD, professor and director of interstitial lung disease at the University of Southern California, said in a company press release. “These preliminary signs of clinical and antifibrotic activity suggest that ENV-101 has the potential to change the trajectory of this otherwise relentless disease.”

In IPF, the accumulation of fibrosis, or scarring, in the lungs causes them to become stiffer and makes it harder to breathe, leading to symptoms like shortness of breath and cough.

Lung scarring in IPF is driven by the excessive activity of myofibroblasts, cells that are involved in wound healing and scar tissue formation. Myofibroblast formation and activation is driven by a signaling cascade called the Hedgehog pathway. ENV-101 is an oral therapy that blocks this pathway, which should reduce scar tissue formation and reverse fibrosis over time.

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Lung function gains seen with ENV-101

The Phase 2a trial, which was recently completed, assessed the safety and efficacy of ENV-101 in 41 adults with IPF. The patients were randomly assigned to receive 200 mg tablets of the treatment, or a placebo, once daily for 12 weeks, or about three months.

According to the presented results, patients treated with ENV-101 saw a significant improvement in lung function, with a mean increase of 1.9% in percent predicted forced vital capacity (ppFVC) and a mean increase of 200 mL in total lung capacity (TLC), over the start of the study, that is, its baseline. The amount of air that can be forcibly exhaled after a deep breath expressed as a percentage of normal is what ppFVC indicates. TLC measures the total volume of air in the lungs after a deep breath.

The patients on a placebo had a mean decline of 1.3% in ppFVC and a mean drop of 56 mL in TLC over the baseline.

Also, 80% of the patients taking ENV-101 saw an improvement in TLC, while 70% of those on a placebo had a TLC decrease.

The trial also assessed the effects of treatment on key measures of lung fibrosis as assessed by high-resolution computed tomography (HRCT). Results showed treatment with ENV-101 significantly decreased the absolute percent of quantitative interstitial lung disease — which measures the extent of lung fibrosis — by 9.4%, compared with a 1.1% increase in the placebo.

The most commonly reported side effects related to ENV-101 were changes in taste (57%), hair loss (52%), and muscle spasms (43%), all mild to moderately severe. No treatment-related serious side effects or clinically meaningful safety findings were reported.

“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 A. Frohna, MD, PhD, Endeavor’s chief medical officer. “We look forward to further evaluating ENV-101’s potential in the upcoming WHISTLE-PF clinical trial.”

The company recently announced the completion of $132.5 million in funding to support the clinical development of ENV-101 in IPF and PPF.