Inhibitor looks promising for drug-resistant HIV

Melbourne biotech Avexa has announced successful results from its Phase IIb trial for apricitabine (ATC), a novel nucleoside reverse transcriptase inhibitor (NRTI) it is developing for the treatment of HIV infection in patients with drug-resistant HIV.

The Phase IIb trial compared the effectiveness of ATC in reducing the viral load of patients with drug-resistant HIV with the effectiveness of lamivudine (3TC), a leading NRTI in widespread use.

A total of 47 patients completed 21-day dosing. Of these 17 patients received 600 mg doses of ATC, 16 received 800 mg doses of ATC and the control group of 14 patients were treated with 3TC.

The results for patients in both ATC cohorts exceeded the Phase IIb trial primary endpoint by a substantial margin, according to a company statement. Patients who received ATC achieved on average a reduction of greater than 0.8 log10 (85%) in the level of HIV in the blood after 21 days treatment compared to a reduction of less than 0.03 log10 in patients treated with 3TC.

Nine patients achieved a greater than 1.5 log10 (97%) reduction after 21 days, with 3 patients achieving a reduction of over 2.0 log10 (99%). One patient achieved a decrease in the amount of virus of more than 2.5 log10 (99.7%) after 21 days on ATC.

Patients with the highest degree of drug resistance still achieved a significant benefit from treatment with ATC. The demonstration of superior activity in this study indicates that ATC will be an effective antiviral drug for the treatment of many drug-resistant patients, including even those most highly resistant, CEO Dr Julian Chick said.

"This is a fantastic result for Avexa," Chick said. "The positive result allows us to continue to progress ATC into Phase III trials and towards commercialisation."

"These outstanding results clearly position ATC to become the most effective and well tolerated NRTI for treatment of drug-resistant HIV," Dr Jonathan Coates, Avexa's CSO, and co-inventor of 3TC, a NRTI marketed by GSK, said.

The emergence of resistance to antiviral drugs is one of the most important reasons for treatment failure. No evidence of mutation in the virus resulting in resistance to ATC was detected over the course of the treatment. This indicates that antiviral resistance to ATC does not occur quickly and gives ATC a significant competitive advantage over several other drugs which can rapidly select for resistance.

"Overall the results of Avexa's Phase IIb clinical trial demonstrate that ATC is a clinically effective antiviral drug that can significantly reduce the replication of the virus in patients infected with drug-resistant HIV," Chick said.

"Moreover, these results demonstrate that ATC is a safe drug not associated with undesirable side effects. There was no evidence of ATC resistant virus emerging over the trial period. These results indicate that ATC has the properties required to position it as the NRTI of choice for the treatment of patients failing their first line or subsequent anti-HIV drug regimens."

Source: Avexa