BioWorld International Correspondent

PARIS - Less than three weeks after asking for the full data file from a Phase II trial of AZD3582 in acute and chronic nociceptive pain, NicOx SA clarified the results after conducting its own preliminary review of the data.

AZD3582 is a COX-inhibiting nitric oxide-donating drug (CINOD) being co-developed with AstraZeneca plc, of London. The companies issued a joint statement Feb. 18 reporting that the trial "did not reach its primary endpoint with respect to gastrointestinal ulcers," although the manager of corporate relations at NicOx, Sylvain Goyon, subsequently told BioWorld International that not only had all the secondary endpoints been met but also that the drug had been active against ulcers as well, albeit not to a statistically significant extent.

Sophia-Antipolis-based NicOx, following its review, confirmed the statistical shortcomings of the trial.

"NicOx and its independent experts have concluded that, because of a lower incidence of gastrointestinal ulcers in the group treated with the reference product than that planned by the protocol (14 percent instead of 20 percent to 25 percent), the trial did not have the statistical power necessary for detecting a significant difference on the trial's principal evaluation criterion, namely the incidence of patients with at least one gastrointestinal ulcer of at least 3 mm," the company said in a prepared release. "As a result, although the incidence of gastrointestinal ulcers in the group treated with AZD3582 was lower than that observed in the group treated with the reference product, the difference did not attain the threshold of statistical significance (p=0.07)."

Regarding secondary endpoints, NicOx said the majority of them were effectively attained and that AZD3582 was generally well tolerated. In particular, there was a statistically significant reduction in the number of gastroduodenal ulcers and erosions, as well as a reduction of gastric ulcers and erosions in relation to the reference product. There also was a reduction of the score expressing the severity of gastroduodenal lesions. NicOx added that the product demonstrated equivalent analgesic efficacy to the reference product in soothing pain due to arthrosis.

NicOx CEO Michele Garufi was upbeat on the assessment.

"On the basis of this preliminary review, the results of this Phase II clinical trial clearly show that the release of nitric oxide improves gastric protection while preserving the analgesic efficacy of the reference treatment," he said. "NicOx remains firmly convinced of the potential of this new class of CINOD compounds." He added, "To ensure a proper interpretation of the results of this clinical trial, NicOx is asking for a more in-depth analysis of the data to be carried out by a panel of independent experts."

However, the clarification of data did not have an immediate impact on NicOx's share price, which has not recovered from the dive it took following the original disclosure of the Phase II results. After tumbling from €9.80 on Feb. 17 to €1.70 on Feb. 20, it was down to €1.54 by March 10 and little changed March 11.

AstraZeneca is co-developing AZD3582 under agreements signed in 1998 and 2002 that give it exclusive worldwide rights to develop, manufacture and sell certain CINODs developed by NicOx. AZD3582 is the most advanced of those products, and AstraZeneca says it remains committed to completing the Phase II development program for the drug.