Elpida® (VM1500) is the prodrug of Elsulfavirine (VM1500A), a new potent non-nucleoside reverse transcriptase inhibitor with unique pharmacokinetic properties (T1/2 is ~8 days). A 20 mg once daily dosing was chosen for further study based on 12-week efficacy, pharmacology and safety data.
Compare the efficacy and safety of an ART regimen including Elpida or Efavirenz (EFV) plus tenofovir/emtracitabine (TDF/FTC). Phase IIb randomized, placebo-controlled, double-blind, multicenter study in ART-naïve HIV-1-infected patients treated for 48 weeks. Patients were randomized 1:1 to receive; 1) Elpida 20 mg QD, or 2) EFV 600 mg QD. All patients were treated with TDF/FTC.
120 patients enrolled, 60 Elpida/60 EFV. Baseline plasma HIV RNA median was 4.7-4.8 log10 copies/ml; median CD4+ T lymphocyte count was 349 and 379 cells/mm3 for Elpida and EFV respectively. A total of 55/60 (91.7%) Elpida and 47/60 (78.3%) EFV (p=0.041) completed treatment. At Week 48 of therapy 45/55 (81%) of Elpida and 35/47 (73.7%) of EFV patients had HIV-1 RNA values <50 copies/ml (MITTI-analysis) and all patients in both groups who completed treatment had HIV-1 RNA value < 400 copies/ml. Patients with baseline HIV-I RNA > 100 000 copies/ml, with HIV RNA <50 copies/mL at week 48 were 14/18 (77.7%) and N15/22 (68.2%) of patients respectively after 48 weeks of therapy. No patient demonstrated virologic failure defined as two consecutive HIV RNA plasma levels of >400copies/ml. CD4+ T lymphocyte counts increased at Week 48 by 179 and 182 cells/mm3 respectively. Median CD4/CD8 ratio increased in both groups from 0.41 to 0.78 and from 0.34 to 0.63 respectively. Study drug-associated adverse events were observed in N22/60 (36.7%) of Elpida patients and 45/58 (77.6%) of EFV patients (p <0.0001). AEs of special interest (CNS disorders, skin disorders) with a frequency > 5% occurred in 31.7% and 62.1% of patients respectively (p = 0.008). The most frequent were headache (15% and 24.1%), dizziness (6.7% and 27.6%), sleep disorders (5% and 20.7%). Only EFV patients had abnormal dreams (17.2%), skin rash (17.2%), and pruritus (5.2%). Only 5 patient discontinued Elpida (2 AE [1 pregnancy], 1 lack of compliance, 1 LTFU, 1 withdrew consent), and 13 patients discontinued EFV (7 AE, 5 LTFU, 1 withdrew consent) because of drug-related AEs.
Elpida was significantly better tolerated than EFV-based therapy offering a safer alternative to EFV-based ART.