Avexa, an Australian biotechnology company, has announced encouraging Phase II study results involving its experimental antiretroviral apricitabine (AVX754). According to a press release generated by the company on March 19, initial three-week results from the study suggest that the nucleoside reverse transcriptase inhibitor (NRTI) has activity against HIV harboring the M184V mutation, known to cause high-level resistance to Epivir® (lamivudine) and Emtriva® (emtricitabine).

AVX-201 is a randomized study of two doses of apricitabine (600 mg or 800 mg twice daily) compared to Epivir (150 mg twice daily) in treatment-experienced HIV-infected patients. Upon entering the clinical trial, all volunteers were on a drug combination containing Epivir and, according to pre-study viral load measurements, were no longer responding to their treatment regimen.  To be enrolled in the study, all patients were required to have evidence of the HIV reverse transcriptase M184V mutation, documented using drug-resistance testing. 

In the first part of the study, patients remained on their failing treatment regimen (including Epivir) or switched their Epivir for apricitabine for a total of 21 days.  After day 21, patients continue to receive either Epivir or apricitabine for up to 24 weeks, but are permitted to change their other antiretrovirals.  After week 24, all patients will be switched off of Epivir and given apricitabine to use in its place.  And after 48 weeks in the clinical trial, patients may elect to enter an extension study (AVX-201E) in which they continue to receive apricitabine in addition to their other antiretrovirals. 

The initial 21-day results were reported by Avexa.  It is important to note that these data have only been made public in the form of a press release generated by the company; data have not yet been presented at a scientific conference or published in a peer-reviewed medical journal. 

Sixty patients were enrolled in the study and 47 patients were analyzed after 21 days of treatment.  Of these, 17 patients were in the 600mg apricitabine group, 16 were in the 800mg group, and 14 patients were in the Epivir group. Approximately one third were female, and approximately half had the highest levels of drug resistance. The majority of the patients were recruited in Argentina, with their ages ranging from 22 to 59.

Patients who received apricitabine achieved, on average, a viral load reduction of greater than 0.8 log after 21 days treatment compared to a reduction of less than 0.03 log in patients maintained on Epivir treatment. Nine patients achieved a greater than 1.5 log reduction, with three patients achieving a reduction of over 2.0 log.  One patient achieved a decrease in the amount of virus of more than 2.5 log after 21 days on apricitabine.

According to the Avexa press release, patients with the highest degree of drug resistance still achieved a significant benefit from treatment with apricitabine.

During the study there were no serious side effects related to the study drug, and no patients stopped treatment during the initial 21-day period due to apricitabine-related side effects. The Avexa press release noted that, thus far, there haven’t been any significant cases of increased amylase levels (an indicator of pancreatitis) or elevated liver enzymes (suggestive of liver toxicity) related to apricitabine treatment. These data, Avexa suggests, demonstrate the good safety profile for apricitabine in the clinical setting.

Full scientific data from the Phase IIb trial will be presented at an upcoming international scientific conference. Until then, Avexa says “the demonstration of superior activity in this study indicates that [apricitabine] will be an effective antiviral drug for the treatment of many drug-resistant patients, including even those most highly resistant.”

According to Avexa CEO Julian Chick, MD, “This is a fantastic result for Avexa.  The positive result allows us to continue to progress ATC into Phase III trials and towards commercialization. The team at Avexa has done a great job and these excellent results show that their hard work has paid off.”