Endeavor BioMedicines has solidified its potential threat to Big Pharma with a phase 2b readout suggesting its Hedgehog inhibitor could become the first drug to reduce lung fibrosis while increasing total lung capacity.
Boehringer Ingelheim and Roche dominate the idiopathic pulmonary fibrosis (IPF) market with their blockbusters Ofev and Esbriet, which are designed to slow the decline of lung function.
But Endeavor is pitching to supplant those incumbents by putting the disease into reverse, courtesy of taladegib. Things were already looking promising in 2024, when the biotech unveiled data from a phase 2a trial that suggested the company may be able to achieve that goal by targeting a type of fibroblast thought to drive IPF.
Now, Endeavor has backed up that argument with a phase 2b study of 213 patients with IPF. The WHISTLE-PF trial met its primary endpoint by demonstrating a statistically significant improvement in percent predicted forced vital capacity (ppFVC)—a measure of how much air a person can forcefully exhale—at 24 weeks when compared to placebo.
A pre-specified analysis of lung function also showed that continued treatment with taladegib resulted in a sustained improvement from baseline in ppFVC over 24 weeks, the company noted.
While Endeavor is holding back detailed data for a future medical meeting, the biotech also pointed out that patients on taladegib experienced “significant improvement” compared with placebo across various biomarkers of IPF severity such as total lung capacity, quantitative total interstitial lung disease and quantitative lung fibrosis.
“The totality of these unprecedented results further supports taladegib’s potential to reverse the course of IPF,” the company summarized.
When it came to safety, the rate of serious adverse events was balanced between the placebo and taladegib arms, according to the biotech.
“The unprecedented results from WHISTLE-PF reinforce our confidence in the potential of taladegib to be the first treatment to reduce fibrosis and improve symptoms for IPF patients,” Endeavor co-founder and CEO John Hood, Ph.D., said in the release.
“The totality of these findings, including statistically significant reductions in fibrosis and improvements in lung function, further distinguish taladegib in the IPF treatment landscape and validate our approach to targeting Hedgehog signaling,” Hood added.
The plan now is for the company to engage with the FDA about a strategy for phase 3, Endeavor Chief Medical Officer Lisa Lancaster, M.D., said.
“As an ILD physician, I’ve seen firsthand how devastating IPF is for patients and their families,” Lancaster added. “Taladegib’s potential to reverse the course of IPF provides hope for patients with this terrible disease.”