Metabolic hits back at drug trial criticism

Metabolic (ASX:MBP) today did its best to salvage its reputation and share price, hitting back at analyst criticism of its Phase II clinical trial results of its obesity drug AOD9604.

The exuberance which greeted its initial announcement to the market on Monday saw shares hit a high of $2.50 before strong selling amid scepticism about the results pushed shares down to $1.21. Today they had regained some ground, up 21 per cent to $1.47 at time of writing. Metabolic also said today it had received requests for meetings and further data from several major international pharmaceutical companies with whom it had already been discussing the project.

In analyses of the results, Dianne Glenn, of investment bank EG Capital, and independent analysts Bioshares queried the statistical significance of the results.

"The results are not as strong as we have anticipated, but the issue is more of whether the results of this trial will satisfy the requirements for the FDA to grant an IND approval for Metabolic to commence the pivotal Phase III trials for AOD9604," Glenn said in her report.

But Metabolic said that its FDA consultant confirmed there was enough efficacy data to satisfy the FDA, if the company performed a lead-in study to confirm the optimal dose prior to commencing Phase III studies. Traditionally Phase II studies are used to determine optimal dose, while Phase III studies are used to generate the efficacy data required for market approval.

The controversy over Metabolic's results has centred around two points. Firstly, the dose-response data in Metabolic's results is puzzling: although the 1mg dose showed the greatest mean weight change of 2.8kg, the second best mean weight change was produced by the highest 30mg dose, with the effect more pronounced men.

"It's a mystery," said Glenn of the dose-response data.

Metabolic did not fully address that conundrum in its statement to the market today, but the company speculated that "it may well be that a dose lower than 1mg will work better." CEO Chris Belyea noted that the 1 mg dose was similar to physiological concentrations of growth hormone.

More importantly, a primary statistical analysis revealed that even for the 1mg group, the weight loss achieved over the placebo group was not enough to reach the minimum acceptable confidence level of 0.05. Instead, the p value for the 1mg dosage group was 0.1 -- too high to be statistically significant.

Metabolic today clarified that the p value of the primary analysis was not statistically significant, saying that "on the results of the primary analysis, there is a 90 per cent chance that the 1mg dose of AOD9604 induces weight loss. If the chance is greater than an industry standard of 95 per cent the result is considered to be 'statistically significant'."

However, the company argued that a secondary statistical analysis -- measured as a rate of weight change -- was statistically significant. "There is greater than a 99 per cent chance that the 1mg dose of AOD9604 induces weight loss," the company said.

Glenn said she stood by her criticism of the results. "The p value compared to placebo suggests that there is a low level of confidence that the weight loss is due to the drug," she said. "I have made a conscious decision not to address [Metabolic's] secondary analysis," she said.

The trial did show that there were no side-effects associated with AOD9604, a problem with other current obesity drugs. It also indicated that fewer subjects receiving the 1mg dose of AOD9604 progressed to type II diabetes. "This result suggests that AOD9604 may have a separate role in glucose management toprevent diabetes onset," said Glenn.

Glenn expressed concern that a further dose-response study required to establish the best dose for the Phase III trial would delay the commencement of the Phase III trial, and consequently the launch of the drug, by at least six months.

Metabolic was at pains to point out that a further dosage trial to be conducted as a lead-in to Phase III trials would "add no more than a few months to the development path".