Immunotherapy is the current hot topic in oncology – so much so that many companies are attempting to rebrand their older drugs to take advantage of the surge in interest. It is more surprising to see this also happening in HIV, but this is the case with Bionor Pharma’s therapeutic HIV vaccine Vacc-4x.
“I wouldn’t necessarily say we’re a vaccine company,” the group's chief executive, David Solomon, tells EP Vantage. “We’re more of an immunotherapy company focused on HIV.” A couple of years ago Bionor was developing Vacc-4x as a monotherapy, but now it is using the vaccine with Celgene’s histone deacetylase inhibitor Istodax.
Istodax is the key to the Norwegian company’s “shock and kill” strategy, Mr Solomon explains. Istodax is approved for lymphoma, but not used in HIV.
When it comes to trying to cure HIV, “the problem is that the virus hides in reservoirs – cells in the skin, brain and gut. Therefore it's not seen by the immune system, so a vaccine wouldn’t work.” These reservoirs are now thought to be a major reason that HIV persists in spite of the success of current anti-retroviral agents.
Shock and awe
Mr Solomon claims that Istodax is able to "flush out" the HIV virus from these hiding places into the patient’s bloodstream – there is some evidencefor this, although the mechanism remains unclear. Then it can be killed, and this is where Vacc-4x comes in – it is designed to generate an immune response to parts of the p24 protein in the virus.
The vaccine has shown some promise as a monotherapy, but ultimately has not been able to eradicate HIV completely. So, although Bionor is not ruling out future monotherapy trials, its current focus is the combination with Istodax.
Vacc-4x is being tested in the 20-patient phase I/IIa Reduc study, which is split into two sections. The first, where patients were administered Istodax alone, has already reported that the drug did indeed reactivate HIV.
And according to the company, interim results from Part B, in which patients also received one dose of Vacc-4x, show the first signs that its strategy could be successful. “Seven of the nine patients from the interim analysis had no viral RNA in the plasma at week 18,” Mr Solomon says.
“And two of the nine only had [detectable levels] at week 16 and 18 – in other words, they were viral RNA-free through the first 14 weeks.” Final results from part B in all 20 patients are expected by the end of the year.
Bionor is already planning the next study, Bioskill, which has a similar design but will take place in additional countries and include more patients – around 100-200, according to Mr Solomon. Slated to start in 2016, results could be available in around two years’ time.
Next up could be a triple combination, perhaps with the current flavour of the month, PD-1 inhibitors. “I think three is the magic number,” the chief executive says, comparing Bionor's approach to anti-retrovirals, which are usually given in combination.
“I would say the same is true in cure. Probably you need a latency reversing agent and an immunotherapy or a vaccine, and I would bet you also need an immunomodulatory agent. Maybe a neutralising antibody against HIV, maybe a PD-1 inhibitor.”
Even so, this “does not mean the combination of two drugs won’t be successful”, Mr Solomon adds. And positive results from the Bioskill trial might spur a partner to get involved.
Interested parties could include Gilead Sciences, Merck & Co and GlaxoSmithKline, which all have latency reversal agents that would play the same role as Istodax. Glaxo is already investigating the shock and kill approach in a joint venture with the University of North Carolina.
But although Bionor is talking to potential partners, Mr Solomon is adamant that the company wants to advance Vacc-4x on its own for a while longer. “Our strategy is to get more data, because then there’s more value for our company and shareholders.”
One compelling factor in favour of Bionor’s approach is likely to be cost. If Vacc-4x can keep patients virus-free for one to two years it could be administered annually for a few thousand dollars per course, compared with tens of thousands per year for the current gold-standard anti-retroviral therapy, HAART.
This would also make the vaccine an attractive option in the developing world – but the cost will likely need to be even lower there.
Even in wealthier nations, healthcare systems are desperate to save money, and patients also want to avoid the side effects and stigma of HIV medications. And in the US the battle against HIV/AIDS is far from being won, contended a recent NEJM article.
If these reasons do not convince big pharma to get involved, simple economics might. “Anti-retrovirals will go off patent [soon] and the big companies need something new,” Mr Solomon says. “We’re part of that feeding chain of innovation.”
|Bioskill||Not yet available|