ViiV Healthcare, the global specialist HIV company majority owned by GSK, with Pfizer Inc. and Shionogi Limited as shareholders, announced the start of two phase III studies designed to evaluate an investigational long-acting, injectable regimen of cabotegravir (ViiV Healthcare) and rilpivirine (Janssen Sciences Ireland UC) for the treatment of HIV-1 infection. The two studies, FLAIR (First Long-Acting Injectable Regimen) and ATLAS (Antiretroviral Therapy as Long-Acting Suppression), will examine the safety and efficacy of monthly dosing with the two-drug, injectable regimen in both treatment-naïve and treatment-experienced patients.

This investigational, long-acting, injectable regimen is being co-developed as part of a collaboration with Janssen Sciences Ireland UC.

While fixed-dose oral combination therapies have advanced HIV treatment by providing streamlined dosing through reduced pill burden, adherence to therapy continues to be essential to achieving viral suppression, and reducing the emergence of resistance mutations. Therefore, it is important that new HIV treatment modalities, such as long-acting, injectable therapies, are investigated, as they may improve adherence and patient outcomes.

John C Pottage, Jr, MD, chief scientific and medical officer, ViiV Healthcare, commented, “Currently the treatment of HIV involves life-long therapy with multiple antiretrovirals, so it is important that we continue to improve on the durability, safety, tolerability, and convenience of treatment regimens. This phase III programme with long-acting cabotegravir and rilpivirine as a potential HIV treatment regimen is part of ViiV Healthcare’s broader development programme evaluating two-drug treatment regimens and we look forward to seeing results from the ATLAS and FLAIR studies in 2018.”

In FLAIR, treatment-naïve patients will be given a 20-week daily oral dolutegravir/abacavir/lamivudine (Triumeq) regimen, and will then be randomised to switch to a regimen of long-acting, injectable cabotegravir and rilpivirine, or remain on oral therapy. In ATLAS, treatment-experienced patients with suppressed viral load will be randomised to switch from their existing antiretroviral therapy (ART) to long-acting, injectable formulations of cabotegravir and rilpivirine or remain on oral ART. Participants will be enrolled from investigative sites across Africa, the Americas, Asia and Europe.

The development of long-acting treatments for HIV forms part of a wider strategy to meet UNAIDS’ ambitious aim of ending the AIDS epidemic by 2030. As adherence to daily oral therapy varies among different populations,1 it is important to continue to evaluate additional treatment options, including regimens that require less frequent dosing, which may support adherence, and potentially improve patient outcomes.

FLAIR is phase III, randomised, open-label, multicentre, parallel-group, non-inferiority study designed to assess the antiviral activity and safety of a two-drug regimen of intramuscular, long-acting, injectable cabotegravir and rilpivirine in treatment-naïve adults living with HIV. The primary endpoint for FLAIR is the proportion of participants with a ‘virologic failure’ endpoint as per FDA Snapshot algorithm at Week 48 (Missing, Switch, or Discontinuation = Failure, Intent-to-Treat Exposed [ITT-E] population).

Approximately 600 treatment-naïve participants will be enrolled.

ATLAS is a phase III, open-label, active-controlled, multicentre, parallel-group, non-inferiority study designed to assess the antiviral activity and safety of a two-drug regimen of long-acting, injectable cabotegravir and rilpivirine dosed every four weeks compared to continuation of current ART of two nucleoside reverse transcriptase inhibitors (NRTIs) plus an integrase inhibitor (INI), non-nucleoside reverse transcriptase inhibitor (NNRTI), or protease inhibitor (PI). The primary endpoint for ATLAS is the proportion of participants with a ‘virologic failure’ endpoint as per FDA Snapshot algorithm at Week 48 (Missing, Switch, or Discontinuation = Failure, Intent-to-Treat Exposed [ITT-E] population).

Approximately 600 participants who are on a stable antiretroviral regimen will be enrolled.

Cabotegravir is an investigational integrase strand transfer inhibitor (INSTI) and is not approved by regulatory authorities anywhere in the world. Cabotegravir is being developed by ViiV Healthcare for the treatment and prevention of HIV and is currently being evaluated as a long-acting, nanosuspension formulation for intramuscular injection and also as a once-daily oral tablet for induction prior to long-acting injection.

Edurant (rilpivirine) is a once daily non-nucleoside reverse transcriptase inhibitor (NNRTI) used for the treatment of human immunodeficiency virus (HIV-1) infection in combination with other antiretroviral agents in antiretroviral treatment-naïve adult patients with a viral load = 100,000 HIV RNA copies/mL.

Rilpivirine was developed by Janssen Sciences Ireland UC, one of the Janssen Pharmaceutical Companies of Johnson & Johnson. Rilpivirine is approved in the US and EU as Edurant as a 25mg tablet taken once-a-day and is always taken with a meal. The overall safety and efficacy profile of rilpivirine is based on phase III clinical studies. The most common side effects of Edurant include: depression, headache, trouble sleeping (insomnia) and rash.

Triumeq is a once-daily dolutegravir-based regimen, containing the un-boosted integrase strand transfer inhibitor (INSTI) dolutegravir and the nucleoside reverse transcriptase inhibitors (NRTIs) abacavir and lamivudine.

Two essential steps in the HIV life cycle are transcription – when the virus turns its RNA copy into DNA – and integration – the moment when viral DNA becomes part of the host cell’s DNA. These processes require two enzymes called reverse transcriptase and integrase. NRTIs and INSTIs interfere with the action of the two enzymes to prevent the virus from replicating. This decrease in replication leads to less virus being available to cause subsequent infection of uninfected cells.

Triumeq is a registered trademark of the ViiV Healthcare group of companies.

Edurant is a registered trademark of Janssen Sciences Ireland UC.