Metabolic obesity drug proven safe in trial

Melbourne biotech company Metabolic Pharmaceuticals announced the results of the Phase IIa clinical trial for its anti-obesity drug AOD9604 today, confirming the safety of the drug.

Managing director Chris Belyea said the company was excited by the results, which pave the way for a larger Phase IIb trial scheduled to begin in the middle of this year.

AOD9604 is a peptide drug based on human growth hormone amino acids 177-191, a region that appears to have an effect on fat metabolism, but not on insulin or growth. Initially developed by Assoc Prof Frank Ng at Monash University, pre-clinical and early phase clinical studies have demonstrated that the drug is safe and appears to reduce body fat.

"Our drug is based on a part of the natural human growth hormone protein so after each dose it will go into the body, send out a molecular signal, naturally enhance fat metabolism and then quickly disappear," said Belyea.

The Phase IIa safety and dose escalation study was performed on 36 obese male volunteers, who received a daily dose of the drug or placebo for a week. Previous safety trials performed on the drug looked at the effects after a single dose. The participants ranged in age from 18 to 54 and from marginally obese (body mass index of 30) to morbidly obese (BMI of 47).

The drug did not appear to have any effects on blood sugar control or growth and an average of 0.5 kg weight loss was observed. The results suggested that the optimum effective daily dose was 10 mg, although doses as high as 60 mg were administered to patients. Older participants (more than 35 years) also lost slightly more weight on average than younger participants, a trend observed in previous trials.

Belyea also said that the only side-effect noted was slight abdominal discomfort at the highest dose. "It doesn't impact the results as it is six times the effective dose [of 10 mg]. But it's the first time we've seen a side-effect," he said.

While the trial endpoint was primarily safety, Belyea said the fact that the weight loss patterns were the same as observed in previous studies suggested that the drug would be effective.

Metabolic is now planning a Phase IIb study to look at weight loss in a group of around 250 volunteers receiving the drug daily for three months. A meeting with the US Food and Drug Administration (FDA) is planned for May, and a toxicology study currently in progress will also be completed at about that time, and the company estimates that the weight loss trial will begin in the middle of the year.

The trial will involve five clinical trial sites around Australia, and will look at the minimum effective dose needed to achieve weight loss.

"The key for us is first to prove it works, and second to find the right dose before we go into Phase III," Belyea said. Although the completion of the trial will depend on the start date and the time required to enrol participants, the company hopes to have completed it by the end of this calendar year.

"If a weight loss of about 0.5 kg per week and the excellent safety profile is confirmed over longer term dosing, AOD9604 will be substantially more effective than existing obesity drugs," he said.

Belyea also said that the company would begin planning for Phase III trials, which would examine the effectiveness of the drug over a longer period of time, before the results of the Phase IIb study were in. The company was looking at options for scaling up the production of the drug, which is currently produced by a synthetic process by a US-based contract manufacturer. Ultimately Metabolic would prefer the drug to be produced in a biological system and was collaborating with Bresagen on an E. coli-based process.

The company is good shape financially, with $AUD8 million in the bank and another $12 million due on the exercise of options by July 31 this year. Belyea said that by May 2004, the company would still have several million dollars available.

While the company was in discussions with a number of pharmaceutical companies, Belyea said he was not ready to make a deal yet, and was taking the view that Metabolic would prove efficacy of the drug before it takes a partner. The potential market for anti-obesity drugs is around $US10 billion.

"We want to do one that impresses the market, not one that's a yawn," he said. The key to a successful offer, Belyea said, would be lots of money up-front, big milestones, control at least to Phase III starting, and control of manufacturing in return for marketing and distribution rights. "That sort of deal would be do-able."