ICAAC 2008: Experimental NRTI Elvucitabine Suppresses HIV as well as Lamivudine at 48 Weeks

While novel classes of antiretroviral drugs such as integrase inhibitors and CCR5 antagonists have received the most attention at recent HIV conferences, new agents in older classes also continue to make their way through the pipeline. At the 48th International Conference on Antimicrobial Agents and Chemotherapy (ICAAC 2008) last week in Washington, DC, researchers presented the latest data on elvucitabine (also known as ACH123,446), a cytosine analog nucleoside reverse transcriptase inhibitor (NRTI) being developed by Achillion Pharmaceuticals. Previous laboratory studies demonstrated potent in vitro activity against wild type HIV-1.

In the prospective Phase 2 study described at the meeting, 77 treatment-naive participants in the U.S. and India were randomly assigned to received 10 mg elvucitabine or 300 mg lamivudine (3TC; Epivir), both administered once daily with 600 mg efavirenz (Sustiva) and 300 mg tenofovir (Viread).

Baseline characteristics were similar between the 2 treatment groups. Most participants (about 80%) were men, the mean age was about 37 years, about 56% were white, about 25% were Asian, and about 17% were black. The mean baseline CD4 count was about 325 cells/mm3 and viral load was about 4.8 log10 copies/mL. All but 3 randomized participants had both baseline and post-baseline HIV RNA measurements.

Results

• 55 patients completed 48 weeks of treatment.

• Treatment discontinuation was more common in the elvucitabine arm than in the efavirenz arm:

• 9 vs 3 drop-outs, respectively, at week 12;
• 5 more in each arm between weeks 12 and 48.

• Reasons for not completing 48 weeks of therapy were:

• physician decision (n = 5);
• voluntary patient withdrawal (n = 5);
• adverse events (n = 4);
• lost to follow-up (n = 4);
• sponsor decision (n = 3);
• patient death (suicide) (n = 1).

• In an intent-to-treat (ITT) analysis at week 48, 65% of patients in the elvucitabine arm and 78% in the lamivudine group had HIV RNA < 50 copies/mL, a difference that fell short of statistical significance (P = 0.07).

• In an as-treated analysis, the respective percentages were 96% vs 97%.

• In the ITT population, viral load fell by 2.8 log10 copies/mL in the elvucitabine arm and by 3.0 log10 copies/mL in the elvucitabine arm.

• At week 48, the elvucitabine arm had a mean CD4 count increase of 132 cells/mm3 compared with 203 cells/mm3 in the lamivudine arm.

• Increases in CD4 percentage were similar, 10% vs 9%, respectively.

• The incidence, frequency, type, and severity of adverse events were similar in the 2 treatment arms.

• 10 patients receiving elvucitabine and 8 taking lamivudine experienced serious adverse events (predominantly not deemed to be drug-related).

These findings led the researchers to conclude that, "Elvucitabine administered in combination with tenofovir and efavirenz demonstrates substantial anti-viral activity."
Elvucitabine provided suitable exposure in all patients, was well tolerated with a favorable safety profile, and resulted in excellent virologic and immunologic responses, they stated.
The study (ACH-015) is scheduled to continue through 96 weeks.

Orlando Immunology Ctr., Orlando, FL; Dr. Saple's Clinic, Mumbai, India; Clinical Res. Puerto Rico, San Juan, Puerto Rico; YRGCare VHS, Chennai, India; Hlth. for Life Clinic, Little Rock, AR; Private Practice, Dallas, TX; Cr. for the Prevention and Treatment of Infections, Pensacola, FL; Achillion Pharmaceuticals, Inc., New Haven, CT.

11/07/08

Reference

E DeJesus, D Saple, J Morales-Ramirez, and others. Elvucitabine Phase II 48 Week Interim Results Show Safety and Efficacy Profiles Similar to Lamivudine in Treatment Naive HIV-1 Infected Patients with a Unique Pharmacokinetic Profile. 48th International Conference on Antimicrobial Agents and Chemotherapy (ICAAC 2008). Washington, DC. October 25-28, 2008. Abstract H-892.