The Australian biotechnology company Avexa said yesterday that its experimental nucleoside analogue apricitabine contributed to viral load suppression below 400 copies/ml in over 80% of patients randomised to receive the drug along with an optimised background regimen after 24 weeks of treatment.
Apricitabine is being compared with 3TC in a phase IIb study in 52 patients who have resistance to 3TC and have failing treatment. Participants were initially randomised to continue 3TC, or take either 600mg or 800mg of ATC twice daily for 21 days, alongside their existing background regimen.
After 21 days the background regimen was changed to include the most potentially active drugs as identified by a resistance test – a so-called optimised background regimen.
Results from the 21-day lead-in phase were presented in July at the Fourth International AIDS Society Conference in Sydney, and showed that ATC treatment was associated with a 0.5 – 0.7 log reduction in viral load after 21 days.
Just under half (48%) of patients in the study have at least three thymidine analogue mutations, a sign of substantial resistance to AZT and d4T, and potentially reduced response to abacavir, ddI and tenofovir.
Twenty-one day results from the study showed no significant difference in viral load reduction between those with three or more TAMs and the average for the group as whole (approximately 0.7 log) in patients who received the higher 800mg dose of ATC. However at the lower 600mg dose the response was markedly poorer in those with three or more TAMs.
After 24 weeks 80% in the ATC arm had viral load below 400 copies/ml and more than 70% had viral load below 50
copies/ml. Viral load values in the 3TC arm were not stated in Avexa’s press release; further data and firmer numbers are due to be presented at an international conference in the near future, the company says.
Only four patients on ATC had sufficient levels of virus for resistance testing at week 24, consistent with the high level of viral suppression achieved in the study, but none of them showed additional mutations in reverse transcriptase.
Patients receiving ATC gained an average of around 150 CD4 cells by week 24, but details of the average baseline CD4 cell count have not been released yet.
ATC was well tolerated, said Avexa, with no serious adverse events linked to the drug so far, and no adverse events reported at all by six of 50 participants in the study up to week 24. Two patients were withdrawn from the study due to unplanned pregnancies.
Avexa says it is now on course to launch phase III licensing studies of ATC, and recently bought the US marketing rights to the drug from Shire, its previous developer. Avexa now owns the worldwide marketing rights to Avexa, giving the small Melbourne-based company greater leverage in its likely search for a global marketing partner.
The drug is likely to be targeted at the growing number of patients who need options beyond first-line therapy, where its apparently favourable toxicity profile and activity in patients with nucleoside analogue cross-resistance make it a potentially important new drug.