Inspire Pharmaceuticals, Inc., a biopharmaceutical company, announced top-line results in a Phase II study of INS37217 Respiratory in patients with mild cystic fibrosis (CF) lung disease. Inspire plans to present additional data from the study at the 18th Annual North American Cystic Fibrosis Conference, which will be held in St. Louis in October.
The study was a double-blind, randomized comparison of three doses of INS37217 Respiratory to placebo in 90 patients with CF at 14 clinical centers in the United States. INS37217 Respiratory or placebo was administered three times daily for 28 days by standard jet nebulizer.
The trial was designed to determine the tolerability of three times daily administration of INS37217 Respiratory in doses up to 60mg. All three doses of INS37217 Respiratory were well-tolerated and 93 per cent of enrolled patients completed the study. The most common adverse event was cough, which occurred in 46 per cent of subjects overall and was comparable across all groups, including placebo.
The study was not powered to demonstrate statistically significant differences between INS37217 Respiratory and placebo with respect to efficacy. However, at the end of four weeks of treatment, subjects receiving INS37217 Respiratory had significantly better lung function compared to patients receiving placebo for FEV1 (p = 0.006), FEF25-75 per cent (p = 0.007) and FVC (p = 0.022). The demonstrated benefit in FEF25-75 per cent is particularly notable given that decline in small airway function, as assessed by FEF25-75 per cent, is the earliest manifestation of CF lung disease. Importantly, Inspire plans to develop INS37217 Respiratory as an early intervention therapy. Inspire has received Orphan Drug Status and Fast Track designations from the Food and Drug Administration (FDA) for INS37217 Respiratory for the CF indication.
Cystic Fibrosis Foundation Therapeutics, Inc. (CFFT), the non-profit drug discovery and development affiliate of the Cystic Fibrosis Foundation, funded the majority of the external costs for the Phase II study. Robert J. Beall, Ph.D., president and CEO of the Cystic Fibrosis Foundation and CFFT, commented, "We are delighted with these results, which far surpassed the success criteria that were set forth as part of the agreement between Inspire and CFFT. We are very pleased that Inspire will be moving forward with this exciting potential product, which addresses the basic CF defect."
The study was conducted in collaboration with the CF Therapeutics Development Network (TDN). Bonnie Ramsey, M.D., director, TDN Coordinating Center, stated, "This is a big win for the CF community and we look forward to working with Inspire on future trials to expedite the development of this early intervention approach for CF patients."
Christy L. Shaffer, Ph.D., Inspire CEO, stated, "The results of this study exceeded our expectations and have provided important scientific support for the concept of INS37217 Respiratory as early intervention therapy. We have the resources needed to advance this program in 2004 and we look forward to continuing to work with the Cystic Fibrosis Foundation and to discussing the program with the FDA in the coming months to gain input on the overall development plan and the design of the next clinical trial."
Cystic fibrosis is a fatal disease involving a genetic mutation that disrupts the cystic fibrosis regulator (CFTR) protein. This protein acts as an ion-specific channel that moves salt and water to the surface of the airways. The defect in this ion channel in CF patients leads to poorly hydrated, thick, mucous secretions in the airways and severely impaired mucociliary clearance. INS37217 Respiratory is believed to enhance the lung's mucosal hydration and mucociliary clearance mechanisms by activating an alternative ion channel that acts in the same way as the defective ion channel in moving salt and water to the surface of the airways. It is well established that mucociliary clearance is impaired early in life in CF patients, and average life expectancy for these patients is early thirties. This unique, early intervention approach is different from the approach of other approved CF products and may be important in intervening in the early clinical course of CF lung disease.