Melbourne-based Biotron (ASX:BIT) has announced a successful outcome for a Phase 2 trial of its lead drug BIT225 in HIV-infected patients in combination with current antiretroviral drugs.
The company said data shows there are significant immunological benefits in patients receiving antiretroviral drugs with BIT225 200mg compared to antiretroviral drugs plus placebo.
"In HIV-infected people, the virus hides in long-lived cells known as macrophages. This cellular source of virus persists even in people taking antiretroviral drugs that result in no detectable virus in their blood," said the company.
"There are serious problems associated with viral persistence. These include an immune system ages more quickly, and there are other problems such as HIV-associated neurocognitive disorder (also known as AIDS-related dementia)."
According to the company, in previously reported laboratory-based studies, BIT225 attacks HIV-1 growing in macrophage cells, resulting in the production of dead virus.
The data from this latest Phase 2 trial (BIT225-009) shows the body’s immune system recognises this dead virus, which triggers a range of changes to the immune cells that fight disease.
The data from this BIT225-009 trial is consistent with the targeting and eradication of HIV-1 virus from these key reservoir cells in the BIT225-treated patients.
"The headline results indicate that BIT225 has had a profound effect on a source of virus that persists in the presence of antiretroviral drugs. Eradication of this virus, produced by long-lived reservoir cells, is central to an eventual HIV cure strategy," said the company.
“This has been a complex trial. Going into it, we knew from laboratory-based studies that BIT225 targets and kills virus that hides in long-lived reservoir cells. The challenge was how to show this in humans," said managing director Dr Michelle Miller.
“No one has done this before, and there were no guidelines to follow. We have had to use a range of techniques to show that BIT225 has done what we expected it to do i.e. clear out virus from these reservoirs. This has included the development and use of new cutting-edge assays, which has been a time-consuming process.
“When we designed this trial, we set up a range of different outcomes to look at. Some of the markers we set out to measure haven’t shown any differences, while others have shown very significant changes – and these changes clearly indicate that BIT225 is having a unique and significant effect in these subjects.
“One aspect we set out to measure was whether the addition of BIT225 could improve clearance of HIV-1 from the blood. Current antiretroviral drugs are extremely efficient at rapidly clearing this virus, and the study confirms this. It was not surprising that no additional discernable reductions in blood virus levels were seen with BIT225, but it was important to measure this. But we saw other significant differences that clearly show BIT225 is doing something new and different to these current antiretroviral drugs.
“We know that antiretroviral drugs do NOT clear cellular reservoirs. HIV-infected people have to take drugs for their lifetime to keep virus under control. This trial shows for the first time that there may be a way to clear one of the main cellular reservoirs. This is a major step to the ultimate goal of curing HIV-1 infection.”
The trial was a double-blind, placebo-controlled study undertaken at trial sites in Thailand. A total of 27 HIV-infected subjects, who had not previously taken any antiretroviral drugs, took once daily doses of BIT225 200mg or placebo for 12 weeks in combination with antiretroviral drugs. At the end of 12 weeks, all continued to take antiretroviral drugs as per standard protocols.