Insmed Announces Positive Top-Line Results from Phase 2 WILLOW Study of INS1007 in Patients with Non-Cystic Fibrosis Bronchiectasis
BRIDGEWATER, NJ, USA I February 3, 2020 - 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.
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.
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.