? The focus of HIV drug development has shifted to convenience following efficacy gains.
? Scientists are years away from a functional cure for HIV.
? Injectable HIV medicines expand options for treatment.
With a recent batch of data in hand on experimental HIV drugs, Brian Woodfall, global head of late development for infectious diseases and vaccines for Johnson & Johnson's Janssen unit, spoke with S&P Global Market Intelligence about the changing landscape of HIV treatment.
Brian Woodfall, global head of late development for infectious diseases and vaccines at J&J
Source: Johnson & Johnson
The company presented several studies at the International AIDS Society conference in Paris, including phase 2 data for what could be the first long-acting, injectable HIV drug, and pivotal phase 3 data for a single-tablet regimen that could rival other reduced-pill regimens in development from Gilead Sciences Inc. and ViiV Healthcare, a majority-owned GlaxoSmithKline plc company.
The single tablet centers on a combination of Janssen's darunavir and Gilead's tenofovir alafenamide, or TAF, along with cobicistat and emtricitabine. Janssen already markets darunavir and cobicistat as Prezcobix in the U.S., while Gilead's TAF and emtricitabine is known as Descovy. The latest trial, known as Emerald, shows the single pill to be comparable to a regimen with these separate drugs and that the pill is as effective as older tenofovir disoproxil fumarate, or TDF, formulations.
The interview has been edited and condensed for clarity.
Do you have confidence that the Emerald study will be able to encourage uptake of the TAF-based formulations from governments and payers that have been hesitant?
Brian Woodfall: I can't speak to reimbursement, as negotiations and discussions happen after approval. But what I can say in regard to TAF is that in this study and another phase 3 pivotal trial for the darunavir single tablet regimen, called the Amber trial, we have incorporated looking at a lot of the elements that are relevant to TAF. We have looked to confirm, if you like, the data Gilead has generated when comparing TDF to TAF, and looked at the potential benefits around kidney function and around bone health.
We've done extensive investigations within the trial to make sure that we have a very good comparison of TAF versus TDF, to support the darunavir-based single tablet regimen going forward.
What are the biggest themes in HIV treatment right now?
We've moved into a period where we have really wanted to focus on convenience. Now that we have combinations that work, that are well-tolerated, we need to make sure that they are possible for long-term, potentially lifelong, use, because nonadherence or partial adherence can be one of the major drivers behind drug resistance.
Drugs like darunavir that have a really high genetic barrier to resistance help to limit the drug resistance developing. But it's really important that these drugs are taken in a continuous and constant manner. That's where single-tablet regiments have the potential, or our once-monthly injectable formulations.
The other two important pillars are developing preventative vaccines and looking towards an actual, or functional, cure. We need to be able to use whatever approaches might be successful to stimulate the immune system to develop its own defense against HIV.
How far are we from a functional cure for HIV?
It's unpredictable. There's a number of different approaches that people are interested in, but we need to start gathering data and learning from experimental research.
It's surely not in the short-term; not the next two, three, four or five years. I hope that in the next two to five years we start to understand some of the mechanisms that may be helpful.
What is the significance of an injectable HIV treatment?
There's two main elements of the innovation here — first is going to two-drug therapy. The oral program of dolutegravir [from ViiV Healthcare] and rilpivirine is the first time that we've seen the two-drug therapy perform as well as a three-drug therapy in maintenance therapy.
The same two-drug approach is being utilized with the injectable. We have rilpivirine now in a long-acting formulation with underlying nanoparticle technology. From ViiV's perspective, they use a very similar model to dolutegravir, called cabotegravir, as an integrated inhibitor in a long-acting formulation. It's a very strong collaboration that we were able to innovate on the two-drug approach for maintenance of HIV, but now in a long-acting injectable — the only long-acting formulation that is being studied, to my knowledge, in the HIV space.
It potentially improves adherence, depending on individuals, and certainly it's a more controlled delivery of the medication. We certainly know from research that we have done in Africa and so on that this may improve the delivery of medication. There's many elements we think injectable can bring to the table that is different from oral, and that expands our options for treatment, to be able to find the best approach for each individual patient depending on their circumstances.