--ALIS currently under FDA Priority Review; PDUFA action date set for September 28, 2018--
BRIDGEWATER, N.J., Aug. 07, 2018 (GLOBE NEWSWIRE) -- Insmed Incorporated (Nasdaq:INSM), a global biopharmaceutical company focused on the unmet needs of patients with rare diseases, today announced that the U.S. Food and Drug Administration's (FDA) Antimicrobial Drugs Advisory Committee voted 12 to 2 in favor of the safety and effectiveness of ALIS (amikacin liposome inhalation suspension) for adults with nontuberculous mycobacterial (NTM) lung disease caused by Mycobacterium avium complex (MAC) who have limited or no treatment options. The committee also voted in favor of the surrogate endpoint of sputum culture conversion used in the Phase 3 CONVERT study being reasonably likely to predict clinical benefit. If approved, ALIS will be the first and only therapy in the U.S. specifically indicated for the treatment of patients with NTM lung disease caused by MAC.
"We are very pleased by the outcome of today's advisory committee meeting, which recognized the role ALIS may be able to play in addressing the significant unmet medical need among patients suffering from NTM lung disease caused by MAC, a chronic, debilitating and potentially fatal infection," said Will Lewis, President and Chief Executive Officer of Insmed.
The advisory committee's recommendation was based on briefing materials developed from Insmed's new drug application (NDA) for ALIS, which was submitted under accelerated approval provisions and includes data from the Phase 3 CONVERT study. The study met its primary endpoint of culture conversion by Month 6 with statistical significance for once-daily ALIS when added to guideline-based therapy (GBT) compared with GBT alone in patients with refractory NTM lung disease due to MAC.
"The patients included in our Phase 3 clinical trial represent the most difficult-to-treat segment of the NTM lung disease population, having already failed treatment with current guideline-based therapy. The committee's favorable recommendation brings us one step closer to providing the first and only FDA-approved treatment for these patients. We look forward to working closely with the FDA as it completes its review of our application," said Paul Streck, M.D., Chief Medical Officer of Insmed.
In a separate vote, the committee voted against the safety and effectiveness of ALIS in the broadest population of adult patients with NTM lung disease caused by MAC.
The FDA is not bound by the committee's recommendation but takes its input into consideration when evaluating whether to approve Insmed's NDA for ALIS, which is currently under Priority Review by the FDA with an action date of September 28, 2018 under the Prescription Drug User Fee Act (PDUFA). The FDA has previously designated ALIS an orphan drug, a breakthrough therapy, and a Qualified Infectious Disease Product (QIDP) under the Generating Antibiotic Incentives Now (GAIN) Act.
About NTM Lung Disease
NTM lung disease is a rare and serious disorder associated with increased rates of morbidity and mortality. There is an increasing prevalence of lung disease caused by NTM and Insmed believes it is an emerging public health concern worldwide. Patients with NTM lung disease may experience a multitude of symptoms such as fever, weight loss, cough, lack of appetite, night sweats, blood in the sputum, and fatigue. Patients with NTM lung disease frequently require lengthy hospital stays to manage their condition. Insmed is not aware of any approved inhaled therapies specifically indicated for refractory NTM lung disease caused by MAC in North America, Japan or Europe. Current guideline-based approaches involve use of multi-drug regimens not approved for the treatment of NTM lung disease, and treatment can be as long as two years or more.
The prevalence of human disease attributable to NTM has increased over the past two decades. In a decade long study (1997 to 2007), researchers found that the prevalence of NTM lung disease in the U.S. was increasing at approximately 8% per year and that NTM patients on Medicare over the age of 65 were 40% more likely to die over the period of the study than those who did not have the disease. In the U.S., Insmed estimates there will be between 75,000 and 105,000 patients with diagnosed NTM lung disease in 2018, of which the Company expects 40,000 to 50,000 will be treated for NTM lung disease caused by MAC. Insmed expects that between 10,000 and 15,000 of these patients will be refractory to treatment. In Japan, Insmed estimates there will be between 125,000 and 145,000 patients with diagnosed NTM lung disease in 2018, with approximately 60,000 to 70,000 of those patients being treated for NTM lung disease caused by MAC and 15,000 to 18,000 of these treated patients being refractory to treatment. Insmed also estimates there will be approximately 14,000 patients with diagnosed NTM lung disease in the EU5 (comprised of France, Germany, Italy, Spain and the United Kingdom) in 2018, of which the Company estimates approximately 4,400 will be treated for NTM lung disease caused by MAC and approximately 1,400 of these treated patients will be refractory to treatment.
ALIS is a novel, inhaled, once-daily formulation of amikacin that is in late-stage clinical development and under regulatory review by the FDA for adult patients with NTM lung disease caused by MAC. Amikacin solution for parenteral administration is an established drug that has activity against a variety of NTM; however, its use is limited by the need to administer it intravenously and by toxicity to hearing, balance, and kidney function. Insmed's advanced pulmonary liposome technology uses charge neutral liposomes to deliver amikacin directly to the lung where it is taken up by the lung macrophages where the NTM infection resides. This prolongs the release of amikacin in the lungs while minimizing systemic exposure, thereby offering the potential for decreased systemic toxicities. ALIS's ability to deliver high levels of amikacin directly to the lung distinguishes it from intravenous amikacin. ALIS is administered once daily using an optimized, investigational eFlow® Nebulizer System manufactured by PARI Pharma GmbH (PARI), a portable aerosol delivery system.
About CONVERT (INS-212) and INS-312
CONVERT is a randomized, open-label, global Phase 3 trial designed to confirm the culture conversion results seen in Insmed's Phase 2 clinical trial of ALIS in patients with refractory NTM lung disease caused by MAC. CONVERT is being conducted in 18 countries at more than 125 sites. The primary efficacy endpoint is the proportion of patients who achieved culture conversion at Month 6 in the ALIS plus GBT arm compared to the GBT-only arm. Patients who achieved culture conversion by Month 6 are continuing in the CONVERT study for an additional 12 months of treatment following the first monthly negative sputum culture. Patients who did not culture convert may have been eligible to enroll in our INS-312 study. INS-312 is a single-arm open-label extension study for patients who completed six months of treatment in the INS-212 study but did not demonstrate culture conversion by Month 6. Under the study protocol, non-converting patients in the ALIS plus GBT arm of the INS-212 study will receive an additional 12 months of ALIS plus GBT. Patients who crossed over from the GBT-only arm of the INS-212 study will receive 12 months of treatment of ALIS plus GBT.
Insmed Incorporated is a global biopharmaceutical company focused on the unmet needs of patients with rare diseases. The Company's lead product candidate is ALIS, which is in late-state development and under regulatory review by the FDA for adult patients with NTM lung disease caused by MAC, which is a rare and often chronic infection that is capable of causing irreversible lung damage and can be fatal. 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 nanoparticle 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.
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