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New long-acting fusion inhibitor albuvirtide plus boosted protease inibitor matches standard triple-drug therapy
Keith Alcorn, 2016-10-28 07:00:00
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 NRTIs in treatment-experienced
patients, the International Congress on Drug Therapy in HIV Infection heard on
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
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 patients (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
patients who had viral load above 500 copies/ml at weeks 24 or 48. One patient
in each study arm developed resistance to lopinavir.
Albuvirtide was well tolerated. The most frequent adverse
event in the albuvirtide arm was diarrhoea (garde 1 or 2 in 7.5% of patients, 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
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