Avexa charts course for Shire drug

Avexa (ASX:AVX) consultant James Sawyer outlined to investors this week the company's plans for its Phase IIb clinical trial of AVX754, the HIV drug it recently acquired from UK company Shire Pharmaceuticals.

Sawyer, who also consulted for Shire for three years on the initial clinical development of the drug, is a physician with substantial experience in the design and implementation of clinical development programs, through roles at pharma companies including Sanofi-Winthrop, AstraZeneca and Roche, and now at consulting company Prism Ideas.

The drug is intended initially to be a second line drug, that is, patients will begin taking AVX754 once they start to show signs of resistance to the first line 3TC treatment.

Avexa plans to complete the Phase IIb trial within 12 months, with the aim of releasing the nucleoside analogue reverse transcriptase inhibitor on the market in 2009, and is currently raising capital to support the trial. According to CEO Julian Chick, the company is still looking at options for the commercialisation of the drug -- including co-development with a partner, or the less attractive option of on-licensing the product. But for the time being, Avexa is focused on getting the drug through Phase IIb trials.

According to Julian Chick, the reason Shire divested itself of AVX754, depsite its promising outlook, was a shift in focus by the UK company to late stage drug development in its core therapeutic areas including CNS, gastrointestinal and renal diseases. But Shire has not given away the drug 100 per cent -- it is taking a AUD$2 million equity stake in the company with the option of acquiring more shares after the Phase IIb trial is completed, as well as retaining the North American marketing rights.

One aspect in their favour, according to Sawyer, is the success rate of HIV drugs that get to this stage of development -- essentially all HIV drugs that enter Phase III clinical trials get to market.

"Completion of the Phase IIb study is high predictive of success," he told Australian Biotechnology News. "There are not many [drug development] areas where you know this early on that it is likely to get to market."

Sawyer said the drug provides a good opportunity for a smaller company like Avexa to break into the lucrative HIV therapeutics market. He drew parallels with US biotech Gilead, which launched an HIV reverse transcriptase inhibitor drug in 2001 that is now bringing in hundreds of millions of dollars annually for the company.

So far, AVX754 has had a smooth ride -- its levels of efficacy are as good if not better than any other similar drug on the market or in clinical trials, it has an excellent safety profile and it can be taken with or without food, making it an easier drug to use and an attractive proposition for both prescribing physicians and patients.

While it can't be co-administered with closely related drug 3TC -- which is an unlikely proposition in any case as 3TC is typically used as a first line drug and AVX754 is intended for use as a second line drug -- there are no problems anticipated with co-administration with other classes of HIV drugs typically included in patient treatment regimes.

No signs of resistance to AVX754 have been observed in the short term patient trials performed to date. In vitro experiments have also indicated that the emergence of resistance to AVX754 is likely to be slow.

"It looks extremely good for treatment experienced patients, which is where we have the clinical need," Sawyer said.

Avexa plans to test the drug in 50-60 patients in the Phase IIb study, with around two-thirds of the participants receiving the drug in place of 3TC therapy, while the control group continues to use the standard 3TC therapy.

"We'll look to show that AVX754 reduces the viral load over a short period of time -- about three weeks," Sawyer said.

"This will provide the scientific rationale to confirm that using AVX754 is better than keeping patients on the 3TC regimen, which is the basis of the Phase III trial."

Phase III trials, which are likely to start in 2006-2007, will take two years to complete. They will look at the safety and efficacy of the drug in the target market: treatment experienced patients who have developed resistance to other nucleoside analogue reverse transcriptase inhibitors.

"Typically patients on the first line treatment eventually start to get an increased viral load and a decreased number of T cells. It's due usually to a specific mutation that makes the virus resistant to 3TC," Sawyer said. "And everyone gets to second line treatment -- it's not a question of whether but when. This drug can be used after 3TC has stopped working."