Toby Maher, MD, PhD: Improving Lung Function with ENV-101 Treatment of Idiopathic Pulmonary Fibrosis

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These late-breaking data on drug candidate ENV-101 were presented at ATS 2024 and resulted from a new study on the drug’s effect on individuals with IPF.

Key lung fibrosis measures and general improvements in lung function over 12 weeks may be observed among individuals with idiopathic pulmonary fibrosis (IPF) as a result of treatment with ENV-101, according to new late-breaking data presented at the American Thoracic Society 2024 (ATS 2024) International Conference.1

Biotechnology company Endeavor BioMedicines had announced these phase 2a findings following the conclusion of a study into ENV-101, an investigational drug candidate formulated to block the Hedgehog (Hh) cellular wound-healing pathway. This pathway is abnormally activated during fibrotic lung diseases and leads to the continuous buildup of scar tissue within patients’ lungs.

In a new interview during ATS 2024, the HCPLive editorial team spoke with the data’s presenter Toby M. Maher, MD, PhD, who serves as professor of medicine and director of interstitial lung disease at the University of Southern California, Los Angeles’s Keck School of Medicine. Maher spoke on the findings on ENV-101 and their implications for IPF patients.

“The Hedgehog pathway is a pathway that is active during embryogenesis, so during the development of the fetus in the womb,” Maher explained. “...It appears that in people who develop pulmonary fibrosis, but also fibrosis of other organs, the Hedgehog pathway reactivates and is switched on again, for whatever reason. So within the fibrotic lung tissue, it again plays a role in proliferation and the generation of fibrotic tissue.”

The phase 2a study was a randomized, double-blind, placebo-controlled clinical trial designed to assess the safety and efficacy data of ENV-101 versus placebo among 41 individuals with IPF at 16 sites within 5 countries. These participants were randomized 1:1 and given 200 mg of ENV-101 or a placebo once-per-day for a total of 12 weeks, with overall safety of ENV-101 being the main endpoint and change in lung function from baseline to the 12-week mark being the secondary endpoint.

Maher highlighted several key findings, such as that those treated with ENV-101 showed statistically significant lung function improvements over the course of the 12-week study, as well as a 1.9% mean improvement in their percent predicted forced vital capacity (ppFVC) from the point of baseline versus a mean decline in ppFVC of 1.3% among those in the placebo arm of the study (P = .035).

There was also a statistically significant total lung capacity (TLC) increase above baseline at the 12-week mark among those in the treatment arm, with a mean increase of 200 mL versus a mean decline of 56 mL for those in the placebo arm (P = .005). 80% of those treated had a TLC increase versus 70% of those who were given a placebo who had a TLC decrease.

“What was particularly exciting with the treatment arm was not only did we see stabilization in lung function, but we actually saw an improvement in lung function over the 12 weeks,” Maher said. “A gradual increase in lung function over that period of time. That’s sort of what distinguishes these data from some of the other trials in the past, where we've either seen slowing down in the rate of disease progression or a best stabilization.”

Maher was later asked about safety and tolerability of the drug. He noted that his team had not observed any major drug-related severe or serious adverse events, which he described as reassuring.

“There were some challenges with tolerability,” Maher said. “We know, from the use of Hedgehog inhibitors in oncology, that this class of drugs is associated with dysgeusia, so change in taste, and also associated with muscle cramps and hair loss. We did see some evidence of those side effects in this population of patients but, at worst, the symptoms were described as graded as mild-to-moderate by investigators. Only in 1 case did a patient discontinue treatments and that patient discontinued because of the altered taste.”

For additional information on this topic, view the full interview segment posted above. To learn more about other late-breaking data presented at ATS 2024, view our conference coverage.

The quotes contained in this interview summary were edited for the purposes of clarity.

Maher has received industry academic funding from Astra Zeneca and GlaxoSmithKline R&D; and consultancy or speaker fees from Astra Zeneca, Bayer, Boehringer Ingelheim, BMS, CSL Behring, Endeavor BioMedicines, Fibrogen, Galapagos, Galecto, GlaxoSmithKline, IQVIA, Merck, Pliant, Pfizer, Qureight, Roche, Sanofi-Aventis, StructureTherapeutics, Trevi and Veracyte. Maher is supported by an NIHR Clinician Scientist Fellowship (NIHR Ref: CS-2013-13-017) British Lung Foundation Chair in Respiratory Research (C17-3).


  1. New Phase 2a Clinical Trial Results Demonstrate Endeavor BioMedicines’ ENV-101 Improved Lung Function and Reversed Key Measures of Lung Fibrosis in Patients With Idiopathic Pulmonary Fibrosis. Endeavor BioMedicines. May 19, 2024. Date accessed: May 20, 2024.