BRIDGEWATER, N.J., Sept. 7, 2020 /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 that final results from the Phase 2 WILLOW study of
brensocatib in patients with non-cystic fibrosis bronchiectasis
(NCFBE) were published online in the New England Journal of
Medicine (NEJM). New data from subgroup analyses of the WILLOW
study also were presented today during a late-breaking clinical
trials session at the virtual European Respiratory Society (ERS)
International Congress 2020. Brensocatib is a novel,
first-in-class, oral, reversible inhibitor of dipeptidyl peptidase
1 (DPP1) being developed by Insmed for the treatment of
bronchiectasis and other inflammatory diseases.
"We are very pleased that NEJM has recognized the significance
of the Phase 2 WILLOW data for patients with NCFBE. These results
demonstrate the potential clinical benefits of directly reducing
neutrophil-mediated inflammation in bronchiectasis—a critical
finding for patients who currently suffer from severe outcomes in
the absence of an approved therapy," said Martina Flammer, M.D., MBA, Chief Medical
Officer of Insmed. "We eagerly anticipate initiating our Phase 3
program for brensocatib in bronchiectasis later this year as we
work to bring this urgently needed solution to patients."
The results published today showed that brensocatib
significantly prolonged time to first pulmonary exacerbation, the
primary endpoint, over the 24-week treatment period for both
treatment doses versus placebo (p=0.03 for the 10 mg group; p=0.04
for the 25 mg group). The risk of exacerbation at any time during
the trial was reduced by 42% for the 10 mg group versus placebo (HR
0.58, p=0.03) and by 38% for the 25 mg group versus placebo (HR
0.62, p=0.046).
Treatment with brensocatib also reduced the rate of pulmonary
exacerbations, a key secondary endpoint. Patients treated with
brensocatib experienced a 36% reduction in the 10 mg arm (p=0.04)
and a 25% reduction in the 25 mg arm (p=0.17), compared with the
placebo arm. In addition, mean concentrations of active neutrophil
elastase (NE) in sputum showed dose-dependent reductions compared
with placebo over the 24-week treatment period.
Importantly, study results were consistent among subgroups based
on age, baseline NE concentrations, prior exacerbation history,
bronchiectasis severity index, and lung function.
"The WILLOW study demonstrated that among patients with NCFBE
who have a history of frequent exacerbations, treatment with
brensocatib significantly prolonged the time to first exacerbation
and reduced the risk of exacerbation over the treatment period.
Annualized rates of exacerbation were also lower compared to
placebo," said lead author James
Chalmers, MBChB, Ph.D., Professor and Consultant Respiratory
Physician at the School of Medicine, University of Dundee, UK. "These results are
critically important given the lack of approved pharmaceutical
therapies to reduce the risk of exacerbation—the major driver of
morbidity and mortality in patients with bronchiectasis. The
results also validate the novel mechanism of action of brensocatib
and highlight the potential benefits of reducing neutrophil serine
protease activity."
In addition to the results published in NEJM, new data from the
WILLOW study were presented today at the ERS International
Congress. Subgroup analyses showed that brensocatib consistently
prolonged time to first exacerbation and reduced rates of
exacerbation among patient subgroups analyzed by baseline disease
severity, P. aeruginosa infection, and sputum NE
concentration. Further, brensocatib reduced the sputum
concentrations of all three neutrophil serine proteases (NSPs)
assessed (NE, proteinase 3, and cathepsin G).
Brensocatib was generally well-tolerated in the WILLOW study.
Rates of adverse events (AEs) leading to drug discontinuation in
patients treated with placebo, brensocatib 10 mg, and brensocatib
25 mg were 11%, 7%, and 7%, respectively. The most common AEs in
patients treated with brensocatib were cough, headache, sputum
increase, dyspnea, infective exacerbation of bronchiectasis, and
diarrhea.
Rates of adverse events of special interest (AESIs) in patients
treated with placebo, brensocatib 10 mg, and brensocatib 25 mg,
respectively, were as follows: rates of skin events (including
hyperkeratosis) were 12%, 15%, and 24%; rates of dental events were
4%, 16%, and 10%; and rates of infections considered AESIs were
18%, 14%, and 17%. Hyperkeratosis was reported in 1/85, 3/81, and
1/89 patients treated with placebo, brensocatib 10 mg, and
brensocatib 25 mg, respectively. The study included extensive
dental evaluations to closely monitor progression of periodontal
disease. The results did not raise a signal about dental
safety. The percentage of patients with change in periodontal
pocket depth ≥2 mm and absolute value of ≥5 mm (the threshold of
concern for periodontal disease) were 12%, 11%, and 12% for
placebo, brensocatib 10 mg, and brensocatib 25 mg, respectively. No
skin or dental adverse events were considered serious.
Brensocatib received breakthrough therapy designation from the
U.S. Food and Drug Administration in June
2020 for the treatment of adult patients with NCFBE for
reducing exacerbations. Insmed plans to initiate a Phase 3 program
for brensocatib in bronchiectasis by the end of 2020.
About WILLOW
WILLOW was a randomized, double-blind, placebo-controlled,
parallel-group, multi-center, multi-national, Phase 2 study to
assess the efficacy, safety and tolerability, and pharmacokinetics
of brensocatib administered once daily for 24 weeks in patients
with non-cystic fibrosis bronchiectasis (NCFBE). WILLOW was
conducted at 116 sites and enrolled 256 adult patients diagnosed
with NCFBE who had at least two documented pulmonary exacerbations
in the 12 months prior to screening. Patients were randomized 1:1:1
to receive either 10 mg or 25 mg of brensocatib or matching
placebo. The primary efficacy endpoint was the time to first
pulmonary exacerbation over the 24-week treatment period in the
brensocatib arms compared to the placebo arm.
About Brensocatib
Brensocatib is a small molecule, oral, reversible inhibitor of
dipeptidyl peptidase I (DPP1) being developed by Insmed for the
treatment of patients with bronchiectasis. 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.
About Non-Cystic Fibrosis Bronchiectasis
Non-cystic fibrosis bronchiectasis (NCFBE) is a severe, chronic
pulmonary disorder 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. NCFBE affects approximately 340,000 to
520,000 patients in the U.S. Today, there are no approved therapies
specifically targeting NCFBE in the U.S., Europe, or Japan.
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, ARIKAYCE®
(amikacin liposome inhalation suspension), is the first and only
therapy approved in the United
States for the treatment of refractory Mycobacterium
avium complex (MAC) lung disease as part of a combination
antibacterial drug regimen for adult patients with limited or no
alternative treatment options. MAC lung disease is a chronic,
debilitating condition that can cause severe and permanent lung
damage. Insmed is also advancing brensocatib, a novel oral
reversible inhibitor of dipeptidyl peptidase 1 with therapeutic
potential in bronchiectasis and other inflammatory diseases, and
treprostinil palmitil, an inhaled formulation of a treprostinil
prodrug that may offer a differentiated product profile for rare
pulmonary disorders, including pulmonary arterial hypertension. For
more information, visit www.insmed.com.
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 timing discussed, projected,
anticipated or indicated in any forward-looking statements. Such
risks, uncertainties and other factors include, among others, the
following: the risk that brensocatib does not prove effective or
safe for patients in future clinical studies, including the
STOP-COVID19 study; business or economic disruptions due to
catastrophes or other events, including natural disasters or public
health crises; impact of the novel coronavirus (COVID-19) pandemic
and efforts to reduce its spread on our business, employees,
including key personnel, patients, partners and suppliers; failure
to successfully commercialize or maintain U.S. approval for
ARIKAYCE, the Company's only approved product; uncertainties in the
degree of market acceptance of ARIKAYCE by physicians, patients,
third-party payors and others in the healthcare community; the
Company's inability to obtain full approval of ARIKAYCE from the
FDA, including the risk that the Company will not timely and
successfully complete the study to validate a PRO tool and complete
the confirmatory post-marketing study required for full approval of
ARIKAYCE; inability of the Company, PARI or the Company's other
third party manufacturers to comply with regulatory requirements
related to ARIKAYCE or the Lamira® Nebulizer System; the
Company's inability to obtain adequate reimbursement from
government or third-party payors for ARIKAYCE or acceptable prices
for ARIKAYCE; development of unexpected safety or efficacy concerns
related to ARIKAYCE or brensocatib; inaccuracies in the Company's
estimates of the size of the potential markets for ARIKAYCE or
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; the
Company's inability to create an effective direct sales and
marketing infrastructure or to partner with third parties that
offer such an infrastructure for distribution of ARIKAYCE; failure
to obtain regulatory approval to expand ARIKAYCE's indication to a
broader patient population; failure to successfully conduct future
clinical trials for ARIKAYCE, brensocatib and the Company's other
product candidates, including due to the Company's limited
experience in conducting preclinical development activities and
clinical trials necessary for regulatory approval and the Company's
inability to enroll or retain sufficient patients to conduct and
complete the trials or generate data necessary for regulatory
approval; risks that the Company's clinical studies will be delayed
or that serious side effects will be identified during drug
development; failure to obtain, or delays in obtaining, regulatory
approvals for ARIKAYCE outside the U.S. or for the Company's
product candidates in the U.S., Europe, Japan
or other markets, including the United
Kingdom as a result of its recent exit from the European
Union; failure of third parties on which the Company is dependent
to manufacture sufficient quantities of ARIKAYCE or the Company's
product candidates for commercial or clinical needs, to conduct the
Company's clinical trials, or to comply with laws and regulations
that impact the Company's business or agreements with the Company;
the Company's inability to attract and retain key personnel or to
effectively manage the Company's growth; the Company's inability to
adapt to its highly competitive and changing environment; the
Company's inability to adequately protect its intellectual property
rights or prevent disclosure of its trade secrets and other
proprietary information and costs associated with litigation or
other proceedings related to such matters; restrictions or other
obligations imposed on the Company by its agreements related to
ARIKAYCE or the Company's product candidates, including its license
agreements with PARI and AstraZeneca AB, and failure of the Company
to comply with its obligations under such agreements; the cost and
potential reputational damage resulting from litigation to which
the Company is or may become a party, including product liability
claims; the Company's limited experience operating internationally;
changes in laws and regulations applicable to the Company's
business, including any pricing reform, and failure to comply with
such laws and regulations; inability to repay the Company's
existing indebtedness and uncertainties with respect to the
Company's ability to access future capital; and delays in the
execution of plans to build out an additional FDA-approved
third-party manufacturing facility and unexpected expenses
associated with those plans.
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, 2019, our Quarterly
Report on Form 10-Q for the quarter ended March 31, 2020 and any subsequent Company filings
with the 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:
Argot Partners
Laura Perry or Heather Savelle
(212) 600-1902
Insmed@argotpartners.com
Media:
Mandy Fahey
Senior Director, Corporate Communications
Insmed
(732) 718-3621
amanda.fahey@insmed.com
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