Inspire Pharmaceuticals Inc. may have hit the end of the road for a Phase II product designed for use in cardiopulmonary bypass procedures.

The company terminated its clinical trial of INS50589 Antiplatelet after an independent Data Monitoring Committee recommended stopping the study due to a range of bleeding complications seen among the initial patients enrolled and treated.

"The DMC did a very thorough analysis of the data, and then made their recommendation in terms of ending the study, and we decided to accept that recommendation," said Jenny Kobin, Inspire's vice president of investor relations and corporate communications. "We expect to be able to review the unblinded data sometime shortly and have more information in terms of really understanding what the observations were."

The company's stock (NASDAQ:ISPH) dipped 28 cents Tuesday, closing at $4.54.

The trial began in April, and results were expected within the first half of 2007. At that point, Inspire "had been hoping to partner this program," Kobin told BioWorld Today. While there is still a possibility that through discussions with the FDA and further analysis of the data, a partner might want to take over development, Inspire most likely will not invest any more of its own time or money in the endeavor.

Internally discovered, INS50589 is a selective and reversible inhibitor of the platelet P2Y12 adenosine diphosphate receptor. Platelets are responsible for starting and maintaining blood clots, but once they are activated during cardiovascular interventions, such as cardiopulmonary bypass, they do not function properly, resulting in postoperative blood loss. INS50589 was designed to reduce the risk of bleeding complications by inhibiting P2Y12 receptors. Phase I data in healthy volunteers showed the compound was well tolerated and demonstrated dose-dependent inhibition of platelet aggregation during infusion, and preclinical data showed it preserved platelet function, reduced postoperative blood loss and reduced the need for transfusions. Kobin said there was no indication of bleeding complications in previous data.

The Phase II proof-of-concept trial - a randomized, double-blind study - was evaluating three doses of INS50589 (0.2, 0.5 and 1 mg/kg/hour) compared to placebo in about 160 patients undergoing CABG surgery at 20 U.S. clinical centers. The DMC's recommendation to terminate the trial at all dose levels was made based on the first 27 patients enrolled. No deaths were reported in the trial, and it is unclear as to whether there were more bleeding complications seen with the higher doses.

The next step for Durham, N.C.-based Inspire is to gain access to the data and conduct an internal analysis to understand the DMC's findings. The company indicated, however, that it would probably not move forward with development of INS50589, but instead "reallocate time and capital to key programs" in the areas of ophthalmology and respiratory/allergy.

"All along we had been hoping to partner this program," Kobin said.

The company is developing Prolacria (diquafosol tetrasodium) for dry-eye syndrome, which has completed four Phase III trials and has received two approvable letters, in December 2003 and December 2005. (See BioWorld Today, Dec. 23, 2003, and Dec. 5, 2005.)

The first approvable letter "suggested running additional trials," which the company did, Kobin said, but the Phase III study "was not successful in hitting the primary endpoint." Inspire took the data and combined it with data from another trial and formally submitted an analysis that company officials thought would support a final approval, but the second approvable letter arrived last December. Kobin said the letter made no mention of additional trials, and Inspire met with the FDA in March, at which time it agreed to provide further information. The company has not specified the kind of information that the FDA is seeking.

Another product in development at Inspire is denufosol tetrasodium (INS37217 respiratory) for cystic fibrosis, which is designed to enhance the lung's innate mucosal hydration and mucociliary clearance through stimulation of the P2Y2 receptor. The company started the first of two pivotal Phase III trials in cystic fibrosis patients in July. Known as TIGER-1, the study includes a 24-week efficacy treatment period, followed by a 24-week safety extension period, and will compare 60 mg of denufosol to placebo by inhalation three times a day in about 350 patients at 70 U.S. sites. The drug has fast-track and orphan drug designations in the U.S., and orphan drug status in Europe.

At the earlier stage, Inspire is developing intranasal epinastine, which it in-licensed from Boehringer Ingelheim International GmbH, of Ingelheim, Germany, in February. It has exclusive rights to develop and market the product in the U.S. and Canada for the treatment or prevention of allergic rhinitis. After filing an investigational new drug application in the coming months, Inspire expects to "start Phase II testing" by the end of the year, Kobin said.

Inspire has plenty of cash to take its programs forward. Second-quarter results released Tuesday showed the company had $99.2 million in cash, cash equivalents and investments as of June 30, and a burn rate of about $4 million a month.

The company also posted $13.4 million in co-promotion revenues for the quarter from Elestat (epinastine HCl ophthalmic solution) for allergic conjunctivitis and Restasis (cyclosporine ophthalmic emulsion) for dry eye. The products were developed by Irvine, Calif.-based Allergan Inc., which partnered with Inspire on Restasis in June 2001, and on Elestat in December 2003. (See BioWorld Today, June 28, 2001.)

Inspire's net loss for the quarter was $5.4 million, or 13 cents per share, compared with $4.7 million, 11 cents per share, for the same period last year.