Washington Editor

Inspire Pharmaceuticals Inc. said a second Phase III study of its product for dry eye has ended with highly statistically significant results, resulting in a 102.7 percent jump in the company's stock.

Inspire's shares (NASDAQ:ISPH) closed Tuesday at $4.50, up $2.28.

The product, INS365, is an eye drop for patients who suffer from chronic dry eye, a painful, burning and irritating condition involving abnormalities and deficiencies in the tear film due to a number of reasons, Inspire, of Durham, N.C., said. There are no pharmacologically active treatments for the condition, commonly found in post-menopausal women.

Data released on Tuesday from Phase III Study 105 indicated that INS365 Ophthalmic 2 percent demonstrated a highly statistically significant improvement (p<0.001) over placebo for the primary objective endpoint of corneal staining.

"We feel we have largely achieved getting this program back on track and we believe that we are continuing to gather evidence to suggest that the product is not only safe, but that it has clear evidence of efficacy, at least on corneal staining," Christy Shaffer, Inspire's CEO, told BioWorld Today. "We feel like we have gained additional information that helps us in terms that we have identified the dose now [2 percent], we understand the time course, we understand the time point in which we can see clear activity and we have a much better understanding of how the product works, when it works and how to differentiate it from placebo such that we should be in a good position to file next year."

In addition to achieving statistically significant results at the primary six-week endpoint, statistical significance was achieved as early as two weeks and was consistently observed throughout the 24-week study, Inspire said. That result is strongly supported by statistically significant results in other secondary objective endpoints such as conjunctival staining. The results are consistent with the results observed in a Phase II trial, 03-103, the company said.

Positive results from Study 105, which looked at 527 patients at 34 U.S. sites, are particularly important for Inspire given that the company has faced some difficulties this year with INS365. The eye drop works by activating the P2Y receptor, a specific receptor on the surface of the eye that is believed to be a physiological regulator of a number of processes in the eye, including natural cleansing.

In January, Inspire's stock tumbled 73 percent to close at $4.13 when the company said the first Phase III for INS365 Ophthalmic, called Study 104, failed to meet its primary efficacy objective. (See BioWorld Today, Jan. 17, 2002.)

Nevertheless, Shaffer said Study 104 produced positive safety data that Inspire intends to use as part of its new drug application scheduled to be filed in the second quarter of 2003. The application also will include data from a third Phase III trial (Study 108) being conducted in a "controlled adverse environment." (See BioWorld Today, April 4, 2002.)

Inspire has enrolled one-third of the patients needed in Study 108, a 200-patient trial designed to compare placebo to INS365 Ophthalmic 2 percent. What makes that trial unique is the controlled adverse environment, meaning factors like humidity are controlled and precise measurements of signs and symptoms of dry eye will be documented. Results are expected in the first quarter of 2003, Shaffer said.

Studies 104 and 105 were similar in their endpoints, patient populations and enrollment (about 500 people each). But Study 104 was a 12-week trial with a nine-month extension for safety. "The primary efficacy outcome in Study 104 failed on the 12-week time point in which the placebo and active [agent] couldn't be differentiated clearly, even though they could at earlier points in time, for example the six-week time point," she said.

After reviewing Study 104 data and trying to learn where it had failed, Shaffer said Inspire and the FDA discussed modifications and developed a final analysis plan for Study 105. "Because 105 had not been unmasked, we had the opportunity to go back to the FDA and clarify exactly how we would analyze the data and what would be acceptable to them as a pivotal study," she said.

One of the key factors in Study 105 involved analyzing data at six weeks. "In this trial we hit the six-week time point with a very good p value, but we also showed statistical significance across a variety of time points, including the final time point at 24 weeks, which is great because this is a chronic drug," she said. "The most important thing, from my perspective, is that if you take those patients who have been on the drug for six months and you remove them from the drug for one week, the corneal staining scores went back to our baseline in the drug-treated group such that you lose the statistical significance between placebo and active."

While that's not the endpoint, Shaffer said it is important because "it tells you that you have clear activity in a receptor-based approach, which is what one would expect."

INS365 is partnered with Irvine, Calif.-based Allergan Inc. in the U.S. and the remainder of the world outside of Asia, where Santen Pharmaceutical Co. Ltd. has the rights. (See BioWorld Today, June 28, 2001.)