Abivax drug could be key to ‘functional cure’ for HIV

Just one year after it was formed, French biopharma company Abivax has started dosing HIV patients in a trial of a new drug that it claims could provide long-lasting control of the infection.

The company claims its approach to treating HIV – which is based on inhibiting a process called RNA splicing in the virus – could provide long-lasting HIV viral load reduction after just a few weeks’ treatment, will not cause resistance and could be dosed less frequently than current antiretroviral drugs.

The new drug – called ABX464 – was developed in collaboration with the laboratory of Professor Jamal Tazi at the University of Montpellier in France, which focuses on the creation of small-molecule drugs that can interrupt machinery HIV exploits to reproduce itself within cells.

The retroviral life cycle requires that significant amounts of RNA remain unspliced in order to carry out functions within the cytoplasm of the cell, so inhibitors of splicing can block the way the virus exploits host cellular processes to reproduce and spread, for example by blocking the production of the viral envelope.

Unlike currently-used antiretrovirals, ABX464 has not generated resistance in animal models of HIV infection even after exposure for 24 weeks, according to Abivax.

The company has already a completed a Phase I trial in healthy volunteers and has now dosed the first HIV-infected patient in a Phase IIa trial in Mauritius that will be followed – if all goes according to plan – by a Phase IIb, multiple dosing study later this year.

“Our platform targeting viral messenger RNA is a new approach in blocking the reproduction of a viru,” said Tazi, who noted that ABX464 appears from animal studies to sustain reductions in viral load for weeks after dosing has stopped, which is not seen with current HIV treatments.

“It provides us with several very promising candidate molecules against HIV and other human pathogenic viruses,” he added.

While the proof of the concept will be in the results of clinical trials, the possible importance of the new therapeutic approach could be significant, according to International AIDS Society president Professor Mark Wainberg.

“If these unique features of ABX464 are confirmed in the clinical development programme in HIV patients that is now underway, ABX464 could become the central element of a functional cure for AIDS,” he said.

HIV therapy has already undergone seismic changes in recent years with the launch of fixed-dose, multi-drug combinations that have simplified dosing regimens and improved compliance, helping people with HIV keep viral load levels under control.

Last year, hopes that high-intensity antiretroviral therapy could provide a functional cure from the infection if started very soon after HIV exposure were dashed by a report in the journal Nature, which suggested HIV can form reservoirs in the body that are protected from antiviral drugs even before the virus is detected in the blood.

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