BRIDGEWATER, N.J., June 24, 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 (formerly INS1007) in patients with non-cystic fibrosis
bronchiectasis (NCFBE) were presented during a virtual American
Thoracic Society (ATS) session titled Breaking News: Clinical
Trial Results in Pulmonary Medicine. Brensocatib is a novel,
oral, reversible inhibitor of dipeptidyl peptidase 1 (DPP1) being
developed by Insmed for the treatment of bronchiectasis and other
inflammatory diseases.
The WILLOW study met its primary endpoint, with brensocatib
significantly prolonging time to first pulmonary exacerbation over
the 24-week treatment period versus placebo (p=0.027 for the 10 mg
group; p=0.044 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=0.029) and by 38% for the 25 mg group
versus placebo (HR 0.62, p=0.046).
Treatment with brensocatib 10 mg also resulted in a significant
reduction in the rate of pulmonary exacerbations, a key secondary
endpoint, versus placebo. Patients treated with brensocatib
experienced a 36% reduction in the 10 mg arm (p=0.041) and a 25%
reduction in the 25 mg arm (p=0.167) versus placebo. Change from
baseline to the end of the treatment period in concentration of
active neutrophil elastase (NE) in sputum demonstrated a
significantly larger reduction with both brensocatib doses versus
placebo (p=0.034 for 10 mg, p=0.021 for 25 mg).
"I am very encouraged by the results from the Phase 2 WILLOW
study, which underscore the potential for brensocatib to reduce the
risk of pulmonary exacerbation in patients with NCFBE," said
presenter and lead study investigator James
Chalmers, MBChB, Ph.D., Professor and Consultant Respiratory
Physician at the School of Medicine, University of Dundee, UK. "These findings are
critically important given the vicious cycle of inflammation, lung
damage, and infection that patients with NCFBE face and the current
lack of approved pharmaceutical therapies."
In addition to the previously reported primary and secondary
endpoint data, Professor Chalmers presented new data today from a
pooled analysis of patients treated with either dosage of
brensocatib in the WILLOW study. This analysis showed that patients
treated with brensocatib who achieved sputum NE below the limit of
quantification post-baseline had a lower incidence of pulmonary
exacerbations compared to patients who had a quantifiable level of
sputum NE post-baseline. Importantly, the risk of having an
exacerbation was 72% lower in these patients.
"We are thrilled to share positive final results from the Phase
2 WILLOW study today, confirming the top-line results presented
earlier this year. These findings are very meaningful for patients
with NCFBE, who currently suffer from severe outcomes in the
absence of an approved therapy," said Martina Flammer, M.D., MBA, Chief Medical
Officer of Insmed. "Importantly, the new data presented today
demonstrate the relationship between NE reduction and risk of
exacerbation and serve as further proof of concept of the potential
of brensocatib and its unique mechanism of action. We look forward
to initiating our Phase 3 program in bronchiectasis while also
exploring the potential of brensocatib in other neutrophil-driven
inflammatory conditions."
Brensocatib was generally well-tolerated in the study. Rates of
adverse events (AEs) leading to discontinuation in patients treated
with placebo, brensocatib 10 mg, and brensocatib 25 mg were 10.6%,
7.4%, and 6.7%, respectively. The most common AEs in patients
treated with brensocatib were cough, headache, sputum increase,
dyspnea, infective exacerbation of bronchiectasis, diarrhea,
fatigue, and upper respiratory tract infection.
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 11.8%, 14.8%, and 23.6%; rates of dental
events were 3.5%, 16.0%, and 10.1%; and rates of infections
considered AESIs were 17.6%, 13.6%, and 16.9%. 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 11.6%,
11.3%, and 12.3% for placebo, brensocatib 10 mg, and brensocatib 25
mg, respectively.
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 in the second half 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 (Formerly INS1007)
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's earlier-stage clinical pipeline includes
brensocatib, a novel oral reversible inhibitor of dipeptidyl
peptidase 1 with therapeutic potential in non-cystic fibrosis
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 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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