BRIDGEWATER, N.J., Feb. 3,
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
positive top-line results from its global, randomized, double-blind
placebo-controlled Phase 2 WILLOW study evaluating the efficacy,
safety, and pharmacokinetics of INS1007 administered once daily in
adults with non-cystic fibrosis bronchiectasis (NCFBE). INS1007 is
a novel, oral, selective, reversible inhibitor of dipeptidyl
peptidase 1 (DPP1).
The WILLOW study met its primary endpoint of time to first
pulmonary exacerbation over the 24-week treatment period for both
the 10 mg and 25 mg dosage groups of INS1007 compared to placebo
(p=0.027, p=0.044, respectively). In addition, treatment with
INS1007 resulted in a reduction in the frequency of pulmonary
exacerbations, a key secondary endpoint, versus placebo.
Specifically, patients treated with INS1007 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 in concentration of active
neutrophil elastase (NE) in sputum versus placebo from baseline to
the end of the treatment period was also statistically significant
(p=0.034 for 10 mg, p=0.021 for 25 mg).
"These results are incredibly encouraging and highlight the
potentially important role INS1007 may play in the management of
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, many bronchiectasis patients suffer from
persistent symptoms and frequent exacerbations, with no
pharmaceutical therapies available that are approved to help them
manage this disease. There is an urgent need for approved,
effective therapies that can break the vicious cycle of
inflammation, lung damage, and infection for these patients."
INS1007 was generally well-tolerated in the study. Rates of
adverse events (AEs) leading to discontinuation in patients treated
with placebo, INS1007 10 mg, and INS1007 25 mg were 10.6%, 7.4%,
and 6.7%, respectively. The most common AEs in patients treated
with INS1007 were cough, headache, sputum increase, dyspnea,
fatigue, and upper respiratory tract infection. Rates of adverse
events of special interest (AESIs) in patients treated with
placebo, INS1007 10 mg, and INS1007 25 mg, respectively, were as
follows: rates of periodontal disease were 2.4%, 7.4%, and 10.1%;
rates of hyperkeratosis were 0%, 3.7%, and 1.1%; and rates of
infections that were considered AESIs were 18.8%, 16.0%, and
16.9%.
"This molecule represents a novel, potentially first-in-class
mechanism that utilizes an anti-inflammatory approach to treat the
debilitating cycle of inflammation, infection, and lung damage
associated with NCFBE," said Martina
Flammer, M.D., MBA, Chief Medical Officer of Insmed.
"Importantly, in addition to achieving the primary and a key
secondary endpoint, we saw significant reductions in sputum
neutrophil elastase, an important biomarker that reflects the
mechanism of action of INS1007. These data provide a strong
rationale for continued development in this disease and potentially
other neutrophil-driven inflammatory conditions. We look forward to
further analyzing the data and discussing next steps with
regulatory authorities."
"The entire Insmed team is elated by the positive results
observed in this study. This is a day of incredible promise for the
hundreds of thousands of patients around the world who currently
suffer from NCFBE. We believe these results further validate both
our business and clinical development capabilities," stated
Will Lewis, Chairman and CEO of
Insmed. "With INS1007, Insmed has a unique and significant
opportunity with a potential first-in-class therapy for NCFBE.
There are currently no approved therapies specifically targeting
this severe and chronic pulmonary disease in the United States, Europe, or Japan."
Insmed plans to present detailed study results at an upcoming
medical meeting. The top-line results will be further discussed on
Insmed's upcoming fourth quarter and year-end 2019 earnings
call.
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 INS1007 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 INS1007 or matching placebo. The
primary efficacy endpoint was the time to first pulmonary
exacerbation over the 24-week treatment period in the INS1007 arms
compared to the placebo arm.
About INS1007
INS1007 is an investigational, first-in-class, oral, selective,
reversible inhibitor of dipeptidyl peptidase I (DPP1) being
developed by Insmed for the treatment of patients with non-cystic
fibrosis bronchiectasis (NCFBE). 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. INS1007 may decrease the
damaging effects of inflammatory diseases such as NCFBE by
inhibiting DPP1 and its activation of NSPs.
About 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 U.S. Today,
there are no approved therapies specifically targeting NCFBE in the
U.S., Europe, or Japan for the treatment of patients with
NCFBE.
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 INS1007,
a novel oral reversible inhibitor of dipeptidyl peptidase 1 with
therapeutic potential in non-cystic fibrosis bronchiectasis and
other inflammatory diseases, and INS1009, 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 the full data set from WILLOW or data
generated in further clinical trials of INS1007 will not be
consistent with the top-line results of WILLOW; 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 the PRO tool and 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 INS1007; inaccuracies in the Company's estimates of the
size of the potential markets for ARIKAYCE or INS1007 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, INS1007 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 the
United Kingdom's 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 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, 2018 and any subsequent
Company filings with the Securities and Exchange Commission.
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 Securities and
Exchange Commission, 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) 487-7468
amanda.fahey@insmed.com
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