Top-Line Efficacy Data
The global CONVERT study met its primary endpoint of culture conversion by Month 6 with statistical and clinical significance. The study demonstrated that the addition of ALIS to guideline-based therapy (GBT) eliminated evidence of NTM lung disease caused by MAC in sputum by Month 6 in 29% of patients, compared to 9% of patients on GBT alone (p < 0.0001). The trial was powered to detect a treatment effect of 15% between the two treatment groups. The CONVERT study enrolled 336 adult patients with NTM lung disease caused by MAC who were refractory to at least six months of GBT. Patients were randomized 2:1 to receive ALIS plus GBT versus GBT alone. The primary endpoint was the proportion of patients achieving culture conversion by Month 6.
"We consider these compelling top-line data to be a remarkable accomplishment in a rare disease state with no currently approved therapies," said
The Company also reported top-line data for several secondary endpoints as of the 6-month timepoint. Top-line data for the 6-minute walk test indicates no statistically significant difference between patients in the two arms. However, an analysis of these data (per a pre-specified endpoint) shows that patients who achieved culture conversion in either arm demonstrated an improvement in 6-minute walk distance when compared to patients who did not culture convert (p=0.0108). Top-line data for the secondary endpoint of time to conversion demonstrated that patients on GBT took approximately 30% longer to convert when compared to patients on ALIS plus GBT (p < 0.0001). The Company is continuing its analysis of the impact of conversion on a variety of other clinical measures.
"I am extremely pleased with and impressed by the culture conversion results that ALIS demonstrated in treatment-refractory patients with NTM lung disease caused by MAC. The eradication of MAC is the first and most important goal for treatment of patients with MAC lung disease," said
"Today marks an important advance in our quest to bring a safe and effective treatment to patients who suffer from NTM lung disease caused by MAC. This represents the first ever global Phase 3 controlled study in patients with NTM, a rare, progressive and destructive infection that is associated with irreversible lung damage and increased rates of mortality," said
Safety and Tolerability
In the study, serious treatment emergent adverse events were similar between treatment arms. There were no distinctions between treatment arms due to hearing loss or renal impairment, side effects commonly associated with intravenous use of amikacin. The overall dropout rate was 16.1%, with an 8.9% dropout rate in the GBT arm and a 19.6% rate in the ALIS plus GBT arm. Overall the rate of reported adverse events in the ALIS plus GBT arm was higher and these events were predominately mild or moderate in nature and generally declined after the second month of treatment. These findings are consistent with the Phase 2 study results and demonstrate adverse events similar to those seen in other clinical studies of inhaled antibiotics.
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About NTM Lung Disease
NTM 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 we believe 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. We are not aware of any approved inhaled therapies specifically indicated for refractory NTM lung disease caused by MAC in
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 in the US 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 US, we estimate there will be between 75,000 and 105,000 patients with diagnosed NTM lung disease in 2018, of which we expect 40,000 to 50,000 will be treated for NTM lung disease caused by MAC. We expect that between 10,000 and 15,000 of these patients will be refractory to treatment. In
ALIS is a novel, inhaled, once daily formulation of amikacin that is in late-stage clinical development for adult patients with treatment-refractory 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.
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 achieve culture conversion at Month 6 in the ALIS plus GBT arm compared to the GBT-only arm. Patients who achieve culture conversion by Month 6 will continue in the CONVERT study for an additional 12 months of treatment following the first monthly negative sputum culture. Patients who do not culture convert have the option of enrolling in our INS-312 study. INS-312 is a single-arm open-label study where patients will receive ALIS plus GBT for 12 months.
This press release contains forward looking statements. "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 factors include, among others: risks that the full six-month data from the CONVERT study or subsequent data from the remainder of the study's treatment and off-treatment phases will not be consistent with the top-line six-month results of the study; uncertainties in the research and development of our existing product candidates, including due to delays in data readouts, such as the full data from the CONVERT study, patient enrollment and retention or failure of our preclinical studies or clinical trials to satisfy pre-established endpoints, including secondary endpoints in the CONVERT study and endpoints in the INS-312 study; lack of safety and efficacy of our product candidates; failure to develop, or to license for development, additional product candidates, including a failure to attract experienced third-party collaborators; failure to obtain, or delays in obtaining, regulatory approval from the
For additional information about the risks and uncertainties that may affect our 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
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