Results show 26 weeks of treatment with
twice-daily 60 mg dose of BMS-986278 resulted in a 69% relative
reduction in the rate of decline in percent predicted forced vital
capacity versus placebo
Treatment effect was consistent with or
without background therapy and BMS-986278 was well tolerated, with
rates of adverse events similar to placebo and low discontinuation
rates
These progressive pulmonary fibrosis
findings, along with the previously reported idiopathic pulmonary
fibrosis cohort results, support continued development of
BMS-986278 in Phase 3 ALOFT program
Bristol Myers Squibb (NYSE: BMY) today announced results from a
Phase 2 study evaluating BMS-986278, a potential first-in-class,
oral, lysophosphatidic acid receptor 1 (LPA1) antagonist in
patients with progressive pulmonary fibrosis (PPF). The study
showed that twice-daily administration of 60 mg of BMS-986278 over
26 weeks reduced the rate of decline in percent predicted forced
vital capacity (ppFVC) by 69% compared to placebo (overall, 38% of
patients in the study received background antifibrotic therapy).
These data will be presented during the Abstracts Leading to
Evolution in Respiratory Medicine Trials (ALERT) session 1 at the
European Respiratory Society (ERS) 2023 International Congress held
September 9-13 in Milan, Italy.
“People living with pulmonary fibrosis are in urgent need of new
treatment options for this devastating disease, which has a median
overall survival of 3-5 years,” said Professor Tamera J. Corte,
clinical trial investigator and Consultant Respiratory Physician
and Director of Interstitial Lung Disease, Department of
Respiratory Medicine, Royal Prince Alfred Hospital. “The Phase 2
progressive pulmonary fibrosis results, which demonstrate
consistent efficacy with or without background antifibrotic therapy
and a favorable tolerability profile, reinforce the potential of
BMS-986278 and highlight advancements in the space as we race to
find a potential new standard of care.”
This Phase 2 study was a global, randomized trial in which
parallel cohorts of patients with idiopathic pulmonary fibrosis
(IPF) and PPF received 30 mg or 60 mg of BMS-986278 or matched
placebo orally twice-daily for 26 weeks. Stable background use of
antifibrotics in the IPF cohort and/or select immunosuppressives in
the PPF cohort were allowed. The primary endpoint of the study was
rate of change in ppFVC from baseline to Week 26 in the IPF cohort.
Rate of change in ppFVC from baseline through 26 weeks in the PPF
cohort was a key secondary endpoint of the study and was assessed
based on two prespecified estimands* (treatment policy estimand and
while-on-treatment estimand).
In the PPF cohort, treatment with 60 mg of BMS-986278 led to a
69% relative reduction in the rate of change in ppFVC versus
placebo in the while-on-treatment analysis (treatment difference
versus placebo 2.9%; 95% CI: 0.4, 5.5), and a 74% relative
reduction versus placebo in the treatment policy analysis (3.2%;
95% CI: 0.7, 5.6). In the 30 mg group, a 42% relative reduction was
observed in the while-on-treatment analysis (1.8%, 95% CI: -0.9,
4.4), and a 37% relative reduction was observed in the treatment
policy analysis (1.6%; 95% CI: −1.0, 4.1). The treatment effect was
consistent in the presence or absence of background antifibrotics
and usual interstitial pneumonia (UIP) pattern (in the placebo, 30
mg and 60 mg groups, 41%, 38% and 36% of patients were on
background antifibrotic therapy, respectively; UIP pattern was
present in 51%, 55% and 50% of patients in the placebo, 30 mg and
60 mg groups, respectively).
Rate of Change in ppFVC from Baseline to Week 26 in the PPF
Cohort
Placebo BID
(n=41)
30 mg BMS-986278 BID
(n=39)
60 mg BMS-986278 BID
(n=42)
Treatment policy strategya
Rate of change in ppFVC,b mean
−4.3
−2.7
−1.1
Rate difference
—
1.6
3.2
95% CI of difference
—
−1.0, 4.1
0.7, 5.6
While-on-treatment strategyc
Rate of change in ppFVC,b mean
−4.2
−2.5
−1.3
Rate difference
—
1.8
2.9
95% CI of difference
—
−0.9, 4.4
0.4, 5.5
aAll observed data regardless of dose
reduction were included and analyzed as randomized.
bLinear mixed model: ppFVC (%) = treatment
+ time + treatment*time + UIP pattern + exposure to
antifibrotics.
cAll observed data prior to dose reduction
were included and analyzed as randomized; data on and after dose
reduction was excluded.
BID, twice-daily; CI, confidence interval;
FVC, forced vital capacity; ppFVC, percent of predicted FVC.
BMS-986278 was well tolerated in both treatment arms of the PPF
cohort, with rates of adverse events (AEs) similar to placebo and
low discontinuation rates. In the placebo, 30 mg and 60 mg arms,
AEs occurred in 78%, 83% and 67% of patients, respectively, while
serious AEs occurred in 32%, 10% and 12% of patients, respectively.
The most frequent AEs in the placebo, 30 mg and 60 mg arms included
diarrhea (15%, 15%, 7%), COVID-19 (5%, 15%, 14%), cough (10%, 8%,
12%) and dyspnea (15%, 5%, 0%). Treatment discontinuation rates due
to AEs were highest in the placebo arm, occurring in 15%, 3% and 0%
of patients in the placebo, 30 mg and 60 mg arms, respectively.
“The results from this innovative study investigating idiopathic
and progressive pulmonary fibrosis give us unprecedented insights
that will inform our scientific understanding of pulmonary fibrosis
and the role of LPA1 inhibition,” said Jonathan Sadeh, MD, MSc,
senior vice president of Immunology Development, Bristol Myers
Squibb. “Our industry-leading drug discovery and development
capabilities and collective results from this Phase 2 study provide
us the expertise and confidence to support continued development of
BMS-986278 in our global Phase 3 ALOFT program in idiopathic and
progressive pulmonary fibrosis.”
Results from the IPF cohort of the Phase 2 study were previously
presented at the American Thoracic Society (ATS) International
Conference in May 2023, showing a 62% relative reduction in the
rate of decline in ppFVC with 60 mg BMS-986278 versus placebo with
or without background therapy. BMS-986278 will now be evaluated in
the global Phase 3 ALOFT (An LPA1 antagonist
for pulmonary Fibrosis Trial) program.
Bristol Myers Squibb would like to thank the patients and
investigators who were involved in this study.
*The treatment policy estimand (similar to
an Intention-to-Treat [ITT] analysis) included all observed data
regardless of dose reduction and provides an estimate of efficacy
with dose reduction as part of the treatment regimen. The
while-on-treatment estimand included all observed data prior to
dose reduction and provides an estimate of efficacy without dose
reduction as part of the treatment regimen. Dose reductions
occurred across all three treatment arms: placebo (n=1), 30 mg
(n=6) and 60 mg (n=5) treatment arms.
About BMS-986278
BMS-986278 is a potential first-in-class, oral, small molecule
lysophosphatidic acid receptor 1 (LPA1) antagonist currently being
evaluated as a novel antifibrotic treatment for patients with
idiopathic pulmonary fibrosis and progressive pulmonary fibrosis.
Increased LPA levels and activation of LPA1 are involved in the
pathogenesis of pulmonary fibrosis. A preclinical in vitro and in
vivo study found that antagonizing LPA1 may be beneficial in
treating lung injury and fibrosis.
About the BMS-986278 Phase 2 Study
This Phase 2 study was a global, randomized study in which
parallel cohorts of patients with idiopathic pulmonary fibrosis
(IPF) and progressive pulmonary fibrosis (PPF) received 30 mg or 60
mg of BMS-986278 or matched placebo orally twice-daily. The study
consisted of a 26-week placebo-controlled treatment period, an
optional 26-week active treatment extension period and a 4-week
post-treatment follow-up period. Patients were permitted to take
background antifibrotics in the IPF cohort and background
antifibrotics and/or immunosuppressants in the PPF cohort. The
primary endpoint was rate of change in percent predicted forced
vital capacity (ppFVC) from baseline to Week 26 in the IPF cohort.
ppFVC compares the observed FVC to that which is expected for a
healthy person of the same age, gender, race and height. Rate of
change in ppFVC from baseline through Week 26 in the PPF cohort was
a key secondary endpoint. Patients who met prespecified blood
pressure reduction criteria were to receive a dose reduction to 10
mg of BMS-986278 or matching placebo twice-daily.
More information can be found on www.clinicaltrials.gov
(NCT04308681).
About Pulmonary Fibrosis
Pulmonary fibrosis is a chronic, life-threatening interstitial
lung disease (ILD) that occurs when lung tissue becomes damaged and
scarred, impacting how lungs function. Progressive pulmonary
fibrosis (PPF) is the preferred term to describe patients who have
an ILD with a progressive fibrotic phenotype. Idiopathic pulmonary
fibrosis (IPF) is the most common type of progressive fibrosing
ILD. As an idiopathic disease, there is no identifiable cause, and
as of 2021, more than 700,000 adults are living with IPF
globally.
Many people living with PPF and IPF are physically impaired,
experience a progressive decline in lung function, have difficulty
performing simple daily activities due to breathlessness and
require continuous supplemental oxygen to ease the burden of normal
breathing.
IPF is a fatal disease with a median survival time of 3-5 years
following diagnosis and 5-year survival rate of approximately 45%;
PPF has shown similar prognosis. Innovation in treatment has been
limited with few new therapies approved in nearly 10 years.
Bristol Myers Squibb: Pioneering Paths Forward in Immunology
to Transform Patients’ Lives
Bristol Myers Squibb is inspired by a single vision –
transforming patients’ lives through science. For people living
with immune-mediated diseases, the debilitating reality of enduring
chronic symptoms and disease progression can take a toll on their
physical, emotional and social well-being, making simple tasks and
daily life a challenge. Driven by our deep understanding of the
immune system that spans over 20 years of experience, and our
passion to help patients, the company continues to pursue
pathbreaking science with the goal of delivering meaningful
solutions that address unmet needs in rheumatology,
gastroenterology, dermatology and pulmonology. We follow the
science, aiming to tailor therapies to individual needs, improve
outcomes and expand treatment options by working to identify
mechanisms with the potential to achieve long-term remission – and
perhaps even cures – in the future. By building partnerships with
researchers, patients and caregivers to deliver innovative
treatments, Bristol Myers Squibb strives to elevate patient care to
new standards and deliver what matters most – the promise of living
a better life.
About Bristol Myers Squibb
Bristol Myers Squibb is a global biopharmaceutical company whose
mission is to discover, develop and deliver innovative medicines
that help patients prevail over serious diseases. For more
information about Bristol Myers Squibb, visit us at BMS.com or
follow us on LinkedIn, Twitter, YouTube, Facebook and
Instagram.
Cautionary Statement Regarding Forward-Looking
Statements
This press release contains “forward-looking statements” within
the meaning of the Private Securities Litigation Reform Act of 1995
regarding, among other things, the research, development and
commercialization of pharmaceutical products. All statements that
are not statements of historical facts are, or may be deemed to be,
forward-looking statements. Such forward-looking statements are
based on current expectations and projections about our future
financial results, goals, plans and objectives and involve inherent
risks, assumptions and uncertainties, including internal or
external factors that could delay, divert or change any of them in
the next several years, that are difficult to predict, may be
beyond our control and could cause our future financial results,
goals, plans and objectives to differ materially from those
expressed in, or implied by, the statements. These risks,
assumptions, uncertainties and other factors include, among others,
that future study results may not be consistent with the results to
date, that BMS-986278 may not receive regulatory approval for the
indication described in this release in the currently anticipated
timeline or at all, that any marketing approvals, if granted, may
have significant limitation on their use, and, if approved, whether
such product candidate for such indication described in this
release will be commercially successful. No forward-looking
statement can be guaranteed. Forward-looking statements in this
press release should be evaluated together with the many risks and
uncertainties that affect Bristol Myers Squibb’s business and
market, particularly those identified in the cautionary statement
and risk factors discussion in Bristol Myers Squibb’s Annual Report
on Form 10-K for the year ended December 31, 2022, as updated by
our subsequent Quarterly Reports on Form 10-Q, Current Reports on
Form 8-K and other filings with the Securities and Exchange
Commission. The forward-looking statements included in this
document are made only as of the date of this document and except
as otherwise required by applicable law, Bristol Myers Squibb
undertakes no obligation to publicly update or revise any
forward-looking statement, whether as a result of new information,
future events, changed circumstances or otherwise.
corporatefinancial-news
View source
version on businesswire.com: https://www.businesswire.com/news/home/20230908930377/en/
Bristol Myers Squibb Media Inquiries: media@bms.com
Investors: investor.relations@bms.com
Bristol Myers Squibb (NYSE:BMY)
Historical Stock Chart
From Oct 2023 to Nov 2023
Bristol Myers Squibb (NYSE:BMY)
Historical Stock Chart
From Nov 2022 to Nov 2023
