—Phase 3 Study Achieves Primary Endpoint for
Both Dosage Strengths of Brensocatib with Statistically Significant
and Clinically Meaningful Reduction in Frequency of Pulmonary
Exacerbations Versus Placebo—
—Treatment with Brensocatib Also Achieves
Statistical Significance on Multiple Secondary Endpoints for Both
Dosage Strengths Versus Placebo—
—Brensocatib Well-Tolerated at Both Dosage
Strengths—
—Results from ASPEN Validate DPP1 Inhibition as New
Mechanism of Action with Potential to Address Range of
Neutrophil-Mediated Diseases—
—Insmed Plans to Advance Quickly Toward U.S.
Regulatory Filing, with Anticipated U.S. Launch in Mid-2025,
Pending Approval—
—Insmed to Host Investor Call at 8:00 am ET on Tuesday, May 28, 2024—
BRIDGEWATER, N.J., May 28, 2024
/PRNewswire/ -- Insmed Incorporated (Nasdaq: INSM), a global
biopharmaceutical company on a mission to transform the lives of
patients with serious and rare diseases, today announced positive
topline results from the ASPEN
study, a global, randomized, double-blind, placebo-controlled Phase
3 study to assess the efficacy, safety, and tolerability of
brensocatib in patients with non-cystic fibrosis bronchiectasis.
The study met its primary endpoint, with both dosage strengths of
brensocatib demonstrating statistically significant reductions in
the annualized rate of pulmonary exacerbations (PEs) versus
placebo. The study also met several of its prespecified secondary
endpoints with statistical significance.
Based on these results, Insmed plans to file a New Drug
Application (NDA) with the U.S. Food and Drug Administration (FDA)
for brensocatib in patients with bronchiectasis in the fourth
quarter of 2024. Pending regulatory approvals, Insmed anticipates a
U.S. launch for brensocatib in mid-2025 followed by launches in
Europe and Japan in the first half of 2026. If approved,
brensocatib would be the first approved treatment for patients with
bronchiectasis as well as the first approved dipeptidyl peptidase 1
(DPP1) inhibitor—a new mechanism of action with the potential to
address a range of neutrophil-mediated diseases.
Topline efficacy results from the ASPEN study are as follows:
|
|
|
|
|
|
|
|
Brensocatib 10
mg
compared to placebo
|
Brensocatib 25
mg
compared to placebo
|
Primary
Endpoint
|
Reduction in annualized
rate of PEs
|
|
|
|
|
|
|
|
21.1 %
|
p=0.0019*
|
19.4 %
|
p=0.0046*
|
Secondary
Endpoints
|
Prolongation of time to
first PE
|
|
|
|
|
|
|
|
18.7 %
|
p=0.0100*
|
17.5 %
|
p=0.0182*
|
Increase in odds of
remaining exacerbation free over 52 weeks
|
|
|
|
|
|
|
|
41.2 %
|
p=0.0059*
|
40.0 %
|
p=0.0074*
|
Change from baseline in
post-bronchodilator forced
expiratory volume in 1 second (FEV1) at week 52
|
|
|
|
|
|
|
|
11 mL
|
p=0.3841
|
38 mL
|
p=0.0054*
|
Reduction in annualized
rate of severe PEs
|
|
|
|
|
|
|
|
25.8 %
|
p=0.1277
|
26.0 %
|
p=0.1025
|
Change from baseline in
the Quality of Life –
Bronchiectasis (QOL-B) Respiratory Score at week 52
|
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|
|
|
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|
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2.0 points
|
p=0.0594
|
3.8 points
|
p=0.0004^
|
*Statistically
significant
|
^Nominally
significant p-value
|
"I am thrilled that the ASPEN
study has demonstrated a statistically significant and clinically
meaningful treatment effect for brensocatib compared with placebo,
underscoring the impact this investigational therapy may have on
patients with bronchiectasis," said lead study investigator
James Chalmers, MBChB, Ph.D.,
Professor and Consultant Respiratory Physician at the School of
Medicine, University of Dundee,
UK. "Today, there is no approved treatment for
bronchiectasis and there remains an urgent need for a therapy that
can reduce exacerbations. As a DPP1 inhibitor, brensocatib would be
the first treatment in its class and could offer a completely new
approach to managing this difficult-to-treat patient population,
heralding a new era in clinical management of bronchiectasis."
As part of the ASPEN study's
conduct, more than 460 trial sites were engaged in nearly 40
countries. After excluding sites that did not enroll any patients
and all sites in Ukraine, the
total number of active sites in ASPEN was 391 sites in 35 countries. Adult
patients (ages 18 to 85 years) were randomized 1:1:1 and adolescent
patients (ages 12 to <18 years) were randomized 2:2:1 for
treatment with brensocatib 10 mg, brensocatib 25 mg, or placebo
once daily for 52 weeks, followed by 4 weeks off treatment. The
primary efficacy analysis included data from 1,680 adult patients
and 41 adolescent patients.
Brensocatib was well-tolerated in the study. Treatment-emergent
adverse events (TEAEs) occurring in at least 5.0% of patients
treated with either dose of brensocatib and more frequently than in
placebo were COVID-19 (15.8%, 20.9%, 15.8%), nasopharyngitis (7.7%,
6.3%, 7.6%), cough (7.0%, 6.1%, 6.4%), and headache (6.7%, 8.5%,
and 6.9%) for brensocatib 10 mg, brensocatib 25 mg, and placebo,
respectively. Additional TEAEs and treatment-emergent adverse
events of special interest (TEAESIs) are as follows:
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|
|
|
|
|
|
|
|
|
|
|
Brensocatib 10
mg
(n=582)
|
Brensocatib 25
mg
(n=574)
|
Placebo
(n=563)
|
Any TEAE, n
(%)
|
|
|
|
|
|
|
|
|
|
|
|
452 (77.7)
|
440 (76.7)
|
448 (79.6)
|
Severe TEAE, n
(%)
|
|
|
|
|
|
|
|
|
|
|
|
74 (12.7)
|
67 (11.7)
|
90 (16.0)
|
Serious TEAE, n
(%)
|
|
|
|
|
|
|
|
|
|
|
|
101 (17.4)
|
97 (16.9)
|
108 (19.2)
|
TEAE leading to death,
n (%)
|
|
|
|
|
|
|
|
|
|
|
|
3 (0.5)
|
4 (0.7)
|
7 (1.2)
|
TEAE leading to
treatment
discontinuation, n (%)
|
|
|
|
|
|
|
|
|
|
|
|
25 (4.3)
|
22 (3.8)
|
23 (4.1)
|
TEAESIs, n
(%)
|
|
|
|
|
|
|
|
|
|
|
|
42 (7.2)
|
56 (9.8)
|
53 (9.4)
|
Hyperkeratosis, n
(%)
|
|
|
|
|
|
|
|
|
|
|
|
8 (1.4)
|
17 (3.0)
|
4 (0.7)
|
Periodontal/gingival
event, n (%)
|
|
|
|
|
|
|
|
|
|
|
|
8 (1.4)
|
12 (2.1)
|
15 (2.7)
|
Severe infection, n
(%)
|
|
|
|
|
|
|
|
|
|
|
|
4 (0.7)
|
7 (1.2)
|
4 (0.7)
|
Pneumonia, n
(%)
|
|
|
|
|
|
|
|
|
|
|
|
23 (4.0)
|
27 (4.7)
|
33 (5.9)
|
"We are incredibly excited about the topline results from the
pivotal ASPEN study and what they
may mean for patients. These findings not only underscore our
belief that brensocatib has the potential to transform the
treatment landscape for bronchiectasis, but they also further
validate DPP1 inhibition as a mechanism that may hold promise in
other neutrophil-mediated diseases," said Martina Flammer, M.D., MBA, Chief Medical
Officer of Insmed. "Today's outcome is the result of years of hard
work and dedication by many members of the Insmed team, and I'd
like to thank them for their efforts. We are especially grateful to
the clinical investigators, site staff, patients, and families who
made this study possible. We now look forward to further analyzing
the data while rapidly advancing toward regulatory filings in our
key regions, where we believe approximately 1 million
bronchiectasis patients may benefit from an approved
treatment."
Brensocatib has received Breakthrough Therapy Designation from
the FDA and was granted access to the Priority Medicines (PRIME)
scheme by the European Medicines Agency for patients with
bronchiectasis. Insmed plans to present detailed results from the
ASPEN study at an upcoming medical
meeting.
Insmed is also advancing the development of brensocatib in other
neutrophil-driven inflammatory diseases with significant health
burdens and limited treatment options. A Phase 2 study in patients
with chronic rhinosinusitis without nasal polyps (CRSsNP) is
currently underway, and Insmed plans to initiate a Phase 2 study in
hidradenitis suppurativa (HS) in the second half of 2024.
Insmed looks forward to hosting a commercial webinar on
Tuesday, June 4, 2024, at
8:00 am ET, where the Company's
commercial leadership will provide details on the market outlook
for its three most advanced programs, ARIKAYCE®
(amikacin liposome inhalation suspension), brensocatib, and
treprostinil palmitil inhalation powder (TPIP).
Conference Call
Insmed management will host a conference call for investors
beginning at 8:00 a.m. ET on Tuesday,
May 28, to discuss the ASPEN
results. Shareholders and other interested parties may participate
in the conference call by dialing (800) 715-9871 (U.S.) or (646)
307-1963 (international) and referencing access code 1245105. The
call will also be webcast live on the Company's website at
www.insmed.com.
A replay of the conference call will be accessible approximately
one hour after its completion through June 27, 2024, by
dialing (800) 770-2030 (U.S.) or (609) 800-9909 (international) and
referencing access code 1245105. A webcast of the call will also be
archived for 90 days under the Investor Relations section of the
Company's website at www.insmed.com.
About Bronchiectasis
Bronchiectasis is a serious, chronic lung disease in which the
bronchi become permanently dilated due to a cycle of infection,
inflammation, and lung tissue damage. The condition is marked by
frequent pulmonary exacerbations requiring antibiotic therapy
and/or hospitalizations. Symptoms include chronic cough, excessive
sputum production, shortness of breath, and repeated respiratory
infections, which can worsen the underlying condition.
Bronchiectasis affects approximately 450,000 patients in the U.S.,
400,000 patients in Europe, and
150,000 patients in Japan, and
there are currently no approved therapies specifically targeting
bronchiectasis in these regions.
About Brensocatib
Brensocatib is a small molecule, oral, reversible inhibitor of
dipeptidyl peptidase 1 (DPP1) being developed by Insmed for the
treatment of patients with bronchiectasis, CRSsNP, and other
neutrophil-mediated diseases. DPP1 is an enzyme responsible for
activating neutrophil serine proteases (NSPs), such as neutrophil
elastase, in neutrophils when they are formed in the bone marrow.
Neutrophils are the most common type of white blood cell and play
an essential role in pathogen destruction and inflammatory
mediation. In chronic inflammatory lung diseases, neutrophils
accumulate in the airways and result in excessive active NSPs that
cause lung destruction and inflammation. Brensocatib may decrease
the damaging effects of inflammatory diseases such as
bronchiectasis by inhibiting DPP1 and its activation of NSPs.
Brensocatib is an investigational drug product that has not been
approved for any indication in any jurisdiction.
About Insmed
Insmed Incorporated is a global biopharmaceutical company on a
mission to transform the lives of patients with serious and rare
diseases. Insmed's first commercial product is a first-in-disease
therapy approved in the United States, Europe,
and Japan to treat a chronic, debilitating lung disease.
The Company is progressing a robust pipeline of investigational
therapies targeting areas of serious unmet need, including
neutrophil-mediated inflammatory diseases and rare pulmonary
disorders. Insmed is also advancing an early-stage research engine
encompassing a wide range of technologies and modalities, including
artificial intelligence-driven protein engineering, gene therapy,
and protein manufacturing. Insmed is headquartered
in Bridgewater, New Jersey, with additional offices and
research locations throughout the United States, Europe,
and Japan. Visit www.insmed.com to learn more.
Forward-Looking Statements
This press release contains forward-looking statements that
involve substantial risks and uncertainties. "Forward-looking
statements," as that term is defined in the Private Securities
Litigation Reform Act of 1995, are statements that are not
historical facts and involve a number of risks and uncertainties.
Words herein such as "may," "will," "should," "could," "would,"
"expects," "plans," "anticipates," "believes," "estimates,"
"projects," "predicts," "intends," "potential," "continues," and
similar expressions (as well as other words or expressions
referencing future events, conditions or circumstances) may
identify forward-looking statements.
The forward-looking statements in this press release are based
upon the Company's current expectations and beliefs, and involve
known and unknown risks, uncertainties and other factors, which may
cause the Company's actual results, performance and achievements
and the timing of certain events to differ materially from the
results, performance, achievements or timings discussed, projected,
anticipated or indicated in any forward-looking statements. Such
risks, uncertainties and other factors include, among others, the
following: the risk that the full data set from the ASPEN study or data generated in further
clinical trials of brensocatib will not be consistent with the
topline results of the ASPEN
study; failure to obtain, or delays in obtaining, regulatory
approvals for brensocatib in the U.S., Europe or Japan; failure to successfully commercialize
brensocatib, if approved by applicable regulatory authorities, in
the U.S., Europe or Japan, or to maintain U.S., European or
Japanese approval for brensocatib once approved; uncertainties in
the degree of market acceptance of brensocatib by physicians,
patients, third-party payors and others in the healthcare
community; inaccuracies in the Company's estimates of the size of
the potential markets for brensocatib or in data the Company has
used to identify physicians; expected rates of patient uptake,
duration of expected treatment, or expected patient adherence or
discontinuation rates; inability of the Company, Esteve
Pharmaceuticals, S.A., Thermo Fisher Scientific, Inc. or the
Company's other third-party manufacturers to comply with regulatory
requirements related to brensocatib; the Company's inability to
obtain adequate reimbursement from government or third-party payors
for brensocatib or acceptable prices for brensocatib; development
of unexpected safety or efficacy concerns related to brensocatib;
failure to obtain regulatory approval for potential future
brensocatib indications; restrictions or other obligations imposed
on us by agreements related to brensocatib, including our license
agreement with AstraZeneca AB, and failure to comply with our
obligations under such agreements; failure to successfully conduct
future clinical trials for brensocatib, including due to the
Company's potential inability to enroll or retain sufficient
patients to conduct and complete the trials or generate data
necessary for regulatory approval, among other things; risks that
the Company's clinical studies will be delayed or that serious side
effects will be identified during drug development; failure of
third parties on which the Company is dependent to manufacture
sufficient quantities of brensocatib for commercial or clinical
needs, to conduct the Company's clinical trials, or to comply with
the Company's agreements or laws and regulations that impact the
Company's business or agreements with the Company; the strength and
enforceability of the Company's intellectual property rights or the
rights of third parties; the cost and potential reputational damage
resulting from litigation to which the Company may become a party,
including product liability claims; changes in laws and regulations
applicable to the Company's business and failure to comply with
such laws and regulations; business or economic disruptions due to
catastrophes or other events, including natural disasters or public
health crises; and inability to repay the Company's existing
indebtedness and uncertainties with respect to the Company's need
and ability to access future capital.
The Company may not actually achieve the results, plans,
intentions or expectations indicated by the Company's
forward-looking statements because, by their nature,
forward-looking statements involve risks and uncertainties because
they relate to events and depend on circumstances that may or may
not occur in the future. For additional information about the risks
and uncertainties that may affect the Company's business, please
see the factors discussed in Item 1A, "Risk Factors," in the
Company's Annual Report on Form 10-K for the year ended
December 31, 2023 and any subsequent
Company filings with the Securities and Exchange Commission
(SEC).
The Company cautions readers not to place undue reliance on any
such forward-looking statements, which speak only as of the date of
this press release. The Company disclaims any obligation, except as
specifically required by law and the rules of the SEC, to publicly
update or revise any such statements to reflect any change in
expectations or in events, conditions or circumstances on which any
such statements may be based, or that may affect the likelihood
that actual results will differ from those set forth in the
forward-looking statements.
Contact:
Investors:
Bryan Dunn
Executive Director, Investor Relations
Insmed
(646) 812-4030
bryan.dunn@insmed.com
Eleanor Barisser
Associate Director, Investor Relations
Insmed
(718) 594-5332
eleanor.barisser@insmed.com
Media:
Mandy Fahey
Executive Director, Corporate Communications
Insmed
(732) 718-3621
amanda.fahey@insmed.com
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