Full Press Release Details
Insmed Announces Positive Top-Line Results from Phase
2 WILLOW Study of INS1007 in Patients with Non-Cystic Fibrosis Bronchiectasis
Achieves Primary Endpoint with Statistically Significant Improvement in Time to First Exacerbation for Both Dosage Strengths
of INS1007 Versus Placebo -
- Treatment with INS1007 also Achieves Key Secondary Endpoint of Reduction of Frequency of Pulmonary Exacerbation -
- INS1007 Was Generally Well-Tolerated at Both Dosage Strengths -
- Company Plans to Advance INS1007 to Phase 3 Development -
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
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.
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
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.
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