New long-acting fusion inhibitor albuvirtide plus boosted protease inibitor matches standard triple-drug therapy

A new fusion inhibitor, albuvirtide, under development in China, combined with a boosted protease inhibitor, proved just as effective as a triple regimen of lopinavir/ritonavir plus two nucleoside reverse transcriptase inhibitors (NRTIs) in treatment-experienced people, the International Congress on Drug Therapy in HIV Infection (HIV Glasgow) heard on Wednesday.

Albuvirtide, a synthetic peptide being developed by Frontier Biotechnologies, is chemically related to enfuvirtide (Fuzeon), and also works by binding to the HIV gp41 envelope protein. Enfuvirtide is now little prescribed, partly due to lack of demand but also because the drug requires an onerous schedule of daily injections and drug preparation that make it unattractive to anyone with other treatment options.

Albuvirtide binds strongly to the human blood protein albumin, which greatly extends the half-life of the drug, so that it can be dosed once-weekly by intravenous infusion. A phase 1 study found that a single infusion of the drug resulted in viral load reduction lasting six to ten days.

Although a weekly infusion may still be problematic for patients, Frontier Biotechnologies is exploring the development of a subcutaneous injectable formulation and would ultimately like to test albuvirtide with one of the long-acting injectable formulations being developed by other companies, as a long-acting combination injectable treatment.

Albuvirtide meets a need for an affordable second- or third-line therapy for China, where the national treatment programme is already treating 400,000 people and expects to treat 770,000 people when treatment is extended to all people with diagnosed infection. With very limited options for second-line treatment, China needs new affordable products.

Albuvirtide was tested in the `Test ALbuvurtide in treatment-Experienced patienTs (TALENT)` study, the first phase III licensing study of a new antiretroviral drug conducted in China.

The study randomised 389 treatment-experienced individuals who had experienced virological failure of a first-line regimen to receive either a weekly infusion of albuvirtide (dose unspecified) plus twice-daily dosing of the boosted protease inhibitor lopinavir/ritonavir, or a regimen of lopinavir/ritonavir twice daily plus two NRTIs: lamivudine and either tenofovir, abacavir or zidovudine, depending on previous treatment history (72% received tenofovir, 26% zidovudine, 1% abacavir and 1% tenofovir and zidovudine).

The protocol-specified interim analysis took place when half of the target recruitment had completed 48 weeks of treatment. The interim analysis reported on 175 people (83 in the albuvirtide arm and 92 in the triple-drug arm). The median age of participants was 40 years, 73% were male, 16% had CD4 cell counts below 100 cells/mm³ and 12% had baseline viral load above 100,000 copies/ml. Baseline resistance to at least one agent was present in 80% of the albuvirtide group and 83% of the NRTI group, most commonly lamivudine resistance. Genotypic resistance to tenofovir was present in 49% of the NRTI group. Protease inhibitor resistance mutations were detected in 3.8% of the albuvirtide group and 2.3% of the NRTI group.

At 48 weeks 80.4% of the albuvirtide group had viral load below 50 copies/ml by intent-to-treat analysis, compared to 66% in the triple-drug group. The albuvirtide arm was non-inferior to the standard triple-drug regimen in second-line treatment.

No resistance to albuvirtide was detected in the five individuals who had viral load above 500 copies/ml at weeks 24 or 48. One participant in each study arm developed resistance to lopinavir.

Albuvirtide was well tolerated. The most frequent adverse event in the albuvirtide arm was diarrhoea (grade 1 or 2 in 7.5% of individuals, compared to 14.1% in the triple-drug arm). Two cases of headache and two of dizziness were observed in the albuvirtide arm.

Elevated cholesterol was observed more frequently in the albuvirtide aim (11.8% vs 0%) but all elevations were grade 1 or 2. Triglycerides were mildly elevated in around a quarter of participants in each arm.

Dr Dong Xie of Frontier Biotechnologies said that whereas participants taking albuvirtide visited the clinic once a week, those in the triple-drug arm visited the clinic only once every three months, suggesting that those in the albuvirtide arm may have received more reinforcement for good adherence and explaining the trend towards superior virological suppression in this group.