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
May 19 2024 - 2:12PM
Business Wire
Data presented for the first time today during
late-breaking oral session at the American Thoracic Society 2024
International Conference
Patients who received ENV-101 experienced
statistically significant improvements in lung function and total
lung capacity, and reversal of multiple key quantitative measures
of lung fibrosis through 12 weeks of treatment
Findings reinforce potential of ENV-101, a
novel investigational Hedgehog (Hh) signaling pathway inhibitor, to
be the first disease-modifying treatment for patients with
idiopathic pulmonary fibrosis
Endeavor BioMedicines, a clinical-stage biotechnology company
developing medicines with the potential to deliver transformational
clinical benefits to patients with life-threatening diseases,
announced 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 (IPF) over a 12-week
period. The results, which also showed that ENV-101 had an
acceptable tolerability profile, were presented for the first time
today in a late-breaking oral session at the American Thoracic
Society 2024 (ATS 2024) International Conference.
“There is a tremendous need for IPF treatments that do more than
slow the inevitable decline of lung function,” said Toby M. Maher,
M.D., Ph.D., 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.”
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.
Key findings from the ENV-101 Phase 2a clinical trial in IPF
presented today at the ATS 2024 International Conference
include:
- Patients who received ENV-101 experienced a statistically
significant improvement in lung function through the 12 weeks of
the trial, with a 1.9% mean improvement in percent predicted forced
vital capacity (ppFVC) from baseline as compared to a mean decline
in ppFVC of 1.3% for patients in the placebo group (P=0.035).
- 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 (P=0.005). In
ENV-101-treated patients, 80% experienced an increase in TLC while
70% of patients who received placebo showed a decrease in TLC.
- The following key measures of lung fibrosis were also evaluated
by high-resolution computed tomography (HRCT):
- Treatment with ENV-101 significantly decreased the absolute
percent of quantitative interstitial lung disease (QILD) from
baseline by 9.4%, as compared to an increase of 1.1% for patients
who received placebo (P<0.05).
- Treatment with ENV-101 decreased the absolute percent of
quantitative lung fibrosis (QLF) by 2% from baseline, as compared
to an increase of 0.87% in patients who received placebo
(P=0.1).
- Treatment with ENV-101 decreased the absolute percent of
quantitative ground glass (QGG) by 4.6% from baseline, as compared
to an increase of 0.29% in patients who received placebo
(P=0.07).
- 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%), alopecia (52%) and muscle spasms (43%), which were all
mild to moderate in severity.
“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,
M.D., Ph.D., Chief Medical Officer, Endeavor BioMedicines. “We look
forward to further evaluating ENV-101’s potential in the upcoming
WHISTLE-PF clinical trial.”
Based on the ENV-101 Phase 2a trial results shared today,
Endeavor BioMedicines intends to initiate the Phase 2 WHISTLE-PF
(Wound-remodeling Hedgehog-inhibitor ILD
Study Testing Lung Function Endpoints
-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 (PPF). Endeavor
BioMedicines recently announced the closing of a $132.5 million
Series C financing that will support clinical development of
ENV-101 in IPF and PPF.
About the ENV-101 Phase 2a Trial The randomized,
double-blind, placebo-controlled Phase 2a clinical trial
(NCT04968574) 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 % quantitative interstitial lung
disease (QILD), % quantitative lung function (QLF) and %
quantitative ground glass (QGG), as measured by high-resolution
computed tomography (HRCT).
About 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 deliver repeated injuries to lung
cells that trigger abnormal wound-healing processes and
life-threatening lung scarring. IPF is a chronic disease with
limited treatment options and a very poor prognosis: the average
life expectancy is only three to five years after diagnosis.
About ENV-101 Endeavor BioMedicines’ investigational
medicine, ENV-101, is a Hedgehog signaling pathway inhibitor. By
binding to and inhibiting a key receptor in the Hedgehog pathway,
ENV-101 is designed to stop the abnormal accumulation of
myofibroblasts that cause fibrosis. This may resolve the excessive
wound-healing process seen in IPF and PPF, creating the potential
to reverse fibrosis and improve lung volume and function.
About Endeavor BioMedicines Endeavor BioMedicines is a
clinical-stage biotechnology company developing medicines with the
potential to deliver transformational clinical benefits to patients
with life-threatening diseases. Endeavor’s lead candidate, ENV-101,
is an inhibitor of the Hedgehog signaling pathway in clinical
development for the treatment of idiopathic pulmonary fibrosis
(IPF) and progressive pulmonary fibrosis (PPF). The company’s
second candidate, ENV-501, is a HER3 antibody-drug conjugate (ADC)
for the treatment of HER3-positive solid tumors. More information
is available at www.endeavorbiomedicines.com and on LinkedIn or
X.
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