Elvucitabine (ACH-126)

Elvucitabine (formerly, ACH-126) is a cytosine analogue similar to 3TC (Epivir) and FTC (Emtriva). It is being developed by Achillion Pharmaceuticals. Interim 48-week data from a phase II trial in treatment-naive patients show elvucitabine (ELV) and 3TC having comparable viral suppression and CD4 cell responses, with a similar safety profile and little difference in side-effects.

Because of its 90-hour half-life, elvucitabine is a good prospect for co-formulation with other antiretrovirals as a once-daily product. A similar phase II trial in treatment-experienced patients is underway. Elvucitabine is also active against hepatitis B virus (HBV).1

Clinical trials

ACH-015 is a 96-week prospective, randomised clinical trial comparing elvucitabine at 10mg once daily to lamivudine (3TC) 300mg once daily (normal dose). Treatment-naive patients from multiple sites in India and US were enrolled. Elvucitabine or 3TC was given in combination with efavirenz (Sustiva) and tenofovir (Viread). In late 2008, results from an interim 48-week analysis were presented.2 

In an intent-to-treat analysis, 65% of patients on the elvucitabine-containing arm had undetectable viral load as compared to 78% on the 3TC arm. This was not a statistically significant difference in the 77 participants.

In the on-treatment analysis of 55 patients who completed 48 weeks, undetectable viral load was reached by 96 and 97% in the elvucitabine and 3TC arms respectively. Increases in CD4 cell percentage were comparable between the two treatment arms (10% increase with elvucitabine versus a 9% increase with 3TC).

There was no significant difference in the incidence, frequency, type, or severity of side-effects (adverse effects, or AEs) between the two drugs: grade 3 or 4 AEs were reported in 9/39 on elvucitabine and 11/37 on 3TC. Serious AEs occurred in 10/39 on elvucitabine and 8/37 on 3TC.

An earlier phase II double-blind study randomly assigned 24 HIV-positive participants to therapy with placebo or 10mg once-daily elvucitabine or placebo. After seven days on elvucitabine monotherapy, patients were given Kaletra for an additional 21 days to reduce the risk of drug resistance. Overall, elvucitabine demonstrated potent activity, was well tolerated, and no major safety issues were identified. Emergence of virus with resistance to elvucitabine or to Kaletra was not observed.3 

In 2005, a small study reported that various doses of elvucitabine plus lopinavir/ritonavir (Kaletra) suppressed HIV RNA by as much 2 log10 copies/ml over 21 days. The short-term safety of elvucitabine was demonstrated, but it was unclear how much of the observed antiviral effect was attributable to the new drug and how much to Kaletra. Accordingly, researchers then carried out a study of elvucitabine used as monotherapy.

Elvucitabine is active against hepatitis B virus and phase II studies are currently evaluating elvucitabine in patients chronically infected with HBV, patients chronically infected with HBV resistant to 3TC (lamivudine, Epivir), and HIV-infected patients with resistance to 3TC.

If elvucitabine proves to be safe and effective, it offers the prospect of an antiviral medication that can be dosed less than once daily.

References

  1. DeJesus E et al. Elvucitabine phase II interim results show safety and efficacy profiles similar to lamivudine in naive HIV-infected patients. Seventeenth International AIDS Conference, Mexico City, abstract TUPE0010, 2008
  2. De Jesus E et al. Elvucitabine phase II 48 week interim results show safety and efficacy profiles similar to lamivudine in treatment naïve HIV-1 infected patients with a unique pharmacokinetic profile. 48th Interscience Conference on Antimicrobial Agents and Chemotherapy, Washington, abstract H-892, 2008
  3. Colucci P et al. Efficacy and novel pharmacology of elvucitabine in a 7 day placebo controlled monotherapy study. 46th Interscience Conference on Antimicrobial Agents and Chemotherapy, ICAAC, San Francisco, abstract H-1670d, 2006
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