Taladegib granted orphan drug status in US, EU for treating IPF
Global Phase 2b trial now testing oral therapy in more than 200 adults
Endeavor Biomedicines’ oral treatment candidate taladegib (ENV-101) has been granted orphan drug designation in the U.S. and the European Union as a treatment for idiopathic pulmonary fibrosis (IPF)
In both regions, orphan drug status is intended to incentivize the development of medications for rare diseases. In the EU, that’s defined as conditions affecting not more than 5 in 10,000 people. In the U.S., rare diseases are categorized as those affecting fewer than 200,000 people.
Orphan drug designation in the EU comes with eligibility for trial protocol assistance, exemptions or reductions in regulatory fees, and 10 years of marketing exclusivity upon therapy approval, if granted. In America, benefits granted by the U.S. Food and Drug Administration, which awards such status, include financial incentives to support clinical development and up to seven years of market exclusivity should the therapy ultimately be approved.
“Receiving orphan drug designation for taladegib in both the United States and [the] European Union underscores the significant unmet medical need for patients with IPF,” Lisa Lancaster, MD, Endeavor’s chief medical officer, said in a company press release. “We are encouraged by the potential of taladegib to reverse the course of disease across multiple measures of IPF, which is a major step forward from current standard-of-care.”
An ongoing Phase 2b trial, called WHISTLE-PF (NCT06422884), is now evaluating the therapeutic potential of taladegib against a placebo in 200 adults, ages 40 and older, with IPF. The trial is recruiting at sites worldwide. According to Endeavor, enrollment is on track, and should be completed next year.
Taladegib designed to improve lung function in IPF patients
IPF, or pulmonary fibrosis due to unknown causes, is characterized by lung inflammation and scarring (fibrosis) that makes it harder to breathe, driving symptoms such as shortness of breath and cough.
While available IPF treatments can help slow lung function decline, they generally aren’t able to entirely stop or reverse disease progression.
Taladegib is an oral therapy that works by blocking the Hedgehog signaling pathway, which plays a role in wound healing and scar tissue formation. Abnormal activation of Hedgehog signaling in IPF is thought to drive lung fibrosis.
By inhibiting Hedgehog signaling, taladegib is expected to stop the abnormal accumulation of cells that cause fibrosis, ultimately resolving excessive scar tissue formation to improve lung function among IPF patients.
Our team … is executing the Phase 2b WHISTLE-PF trial with a remarkable sense of purpose, driven by our mission to push the boundaries of what is possible and restore hope to patients and their families.
In an earlier Phase 2a trial (NCT04968574), taladegib was found to significantly improve lung function relative to a placebo after three months of treatment among adults with IPF. The therapy, which was generally well tolerated by participants, also significantly reduced key indicators of lung fibrosis.
More recent analyses of chest imaging data culled from that study provided further evidence that taladegib can reverse signs of lung disease that are linked to disease progression and prognosis.
Data from that trial had supported the launch of WHISTLE-PF, which started dosing participants late last year.
WHISTLE-PF testing 3 therapy doses against a placebo
In WHISTLE-PF, adults with the disease are being randomly assigned to receive one of three taladegib doses or a placebo, taken as once daily oral tablets, for 24 weeks, or about six months. Stable regimens of standard-of-care IPF medications can also be continued.
The study’s main goal is to evaluate the rate of change in percent predicted forced vital capacity — a measure of lung function — over the six-month period. Patient-reported measures of IPF symptoms, as well as chest imaging to evaluate lung function, capacity, and fibrosis, will also be evaluated as secondary trial goals.
“I am very proud of our team, which is executing the Phase 2b WHISTLE-PF trial with a remarkable sense of purpose, driven by our mission to push the boundaries of what is possible and restore hope to patients and their families,” Lancaster said.
WHISTLE-PF is expected to finish in 2026.
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