ViiV Healthcare, the global specialist HIV company majority owned by GSK, with Pfizer and Shionogi Limited as shareholders, announced the submission of a marketing authorisation application (MAA) to the European Medicines Agency (EMA) for the investigational, once-monthly, injectable cabotegravir, which will be used in combination with Janssen’s once-monthly, injectable rilpivirine to treat HIV-1 infection in adults whose viral load is suppressed and who are not resistant to cabotegravir or rilpivirine.
The application also includes data for cabotegravir oral tablets, intended for use as oral lead-in therapy prior to the commencement of injectable therapy.
Deborah Waterhouse, CEO of ViiV Healthcare, said: “ViiV Healthcare is proud to be sending a regulatory submission to the EMA for what will be a first-of-its-kind treatment. If approved, this long-acting, injectable regimen of cabotegravir and rilpivirine has the potential to give people living with HIV one month between doses with similar safety and efficacy as today’s standard of care – an oral, 3-drug regimen taken every day. We are excited to be one step closer to delivering this long-acting therapy to patients in Europe.”
The submission is based on the global ATLAS (Antiretroviral Therapy as Long-Acting Suppression) and FLAIR (First Long-Acting Injectable Regimen) pivotal phase III studies that included more than 1,100 patients from 16 countries and demonstrated the combination of cabotegravir and rilpivirine, injected monthly, was as effective as a daily, oral, 3-drug regimen in maintaining viral suppression throughout the 48-week study period. The ATLAS and FLAIR studies are part of ViiV Healthcare’s innovative clinical trial programme for 2-drug regimens (2DRs).
Kimberly Smith, M.D., Head of Global Medical Research and Strategy at ViiV Healthcare, said: “This regulatory submission supports ViiV Healthcare’s commitment to developing new and innovative options for people living with HIV to manage their virus. We are proud to be at the forefront of this innovation for patients by potentially changing the frequency of therapy from 365 days per year to just 12.”
This application to the EMA follows the recent submission of a New Drug Application (NDA) for the 2DR of cabotegravir and rilpivirine, as well as cabotegravir oral tablets, to the US Food and Drug Administration (FDA) in April 2019.
In June, this submission was granted a Priority Review Designation by the FDA with an expected action date of December 29, 2019. ViiV Healthcare and Janssen also plan to submit additional regulatory applications for cabotegravir and rilpivirine to other regulatory agencies in the coming months.
ATLAS (NCT02951052) is a phase III, open-label, active-controlled, multicentre, parallel-group, non-inferiority study designed to assess the antiviral activity and safety of a 2-drug regimen of long-acting, injectable cabotegravir and rilpivirine, dosed every four weeks, compared to continuation of current oral anti-retroviral therapy (ART) of two nucleoside reverse transcriptase inhibitors (NRTIs) plus an integrase strand transfer inhibitor (INI), non-nucleoside reverse transcriptase inhibitor (NNRTI), or protease inhibitor (PI) among virally suppressed individuals. The primary endpoint for ATLAS is the proportion of participants with plasma HIV-1 RNA ≥50 c/mL per the FDA Snapshot algorithm at Week 48 (Missing, Switch, or Discontinuation = Failure, Intent-to-Treat Exposed [ITT-E] population). Subjects were required to be virally suppressed for six months or greater, on first or second regimen, with no prior failure.
FLAIR (NCT02938520) is a phase III, randomised, open-label, multicentre, parallel-group, non-inferiority study designed to assess the antiviral activity and safety of a 2-drug regimen of intramuscular, long-acting, injectable cabotegravir and rilpivirine in virologically suppressed adults living with HIV, following 20 weeks of induction therapy with Triumeq (abacavir, dolutegravir and lamivudine tablets). The primary endpoint for FLAIR is the proportion of participants with plasma HIV-1 RNA ≥50 c/mL per the FDA Snapshot algorithm at Week 48 (Missing, Switch, or Discontinuation = Failure, Intent-to-Treat Exposed [ITT-E] population).
Cabotegravir is an investigational integrase inhibitor (INI) 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. It is being evaluated as a long-acting formulation for intramuscular injection and also as a once-daily oral tablet for use as a lead-in, to establish the tolerability of cabotegravir prior to long-acting injection.
EDURANT (rilpivirine) is a once-daily non-nucleoside reverse transcriptase inhibitor (NNRTI) used for the treatment of HIV-1 infection in combination with other antiretroviral agents in antiretroviral treatment-naïve patients 12 years of age and older and weighing at least 35-kg with a viral load ≤ 100,000 HIV RNA copies/mL. Long-acting, injectable rilpivirine is not approved by regulatory authorities anywhere in the world.
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 most common side effects of EDURANT include: depression, headache, trouble sleeping (insomnia) and rash.
Source: Company Press Release