22 January 2021 - - The US Food and Drug Administration has approved Cabenuva, the first and only complete long-acting regimen for the treatment of HIV-1 infection in adults, UK-based specialist HIV company ViiV Healthcare said.

ViiV Healthcare is majority owned by UK-based GlaxoSmithKline plc (NYSE: GSK), with US-based Pfizer Inc. (NYSE: PFE) and Japan-based Shionogi Ltd (OTC: SGIOF).

Cabenuva is provided as a co-pack with two injectable medicines, ViiV Healthcare's cabotegravir and Janssen's rilpivirine, dosed once monthly, as an option to replace the current antiretroviral regimen in those who are virologically suppressed (HIV-1 RNA less than 50 copies per milliliter [mL]) on a stable regimen, with no history of treatment failure, and with no known or suspected resistance to either cabotegravir or rilpivirine.

Prior to initiating treatment of Cabenuva, oral dosing of cabotegravir and rilpivirine should be administered for approximately one month to assess the tolerability of each therapy.

The approval of Cabenuva is based on the pivotal phase III ATLAS (Antiretroviral Therapy as Long-Acting Suppression) and FLAIR (First Long-Acting Injectable Regimen) studies that included more than 1,100 patients from 16 countries.

Prior to initiating treatment with Cabenuva, oral dosing of cabotegravir and rilpivirine (lead-in) was administered for approximately one month to assess the tolerability of each therapy.

In these studies, Cabenuva was as effective in maintaining viral suppression as continuing a daily oral three-drug regimen when injected intramuscularly in the buttocks once a month throughout the 48-week study period.

In both studies, the most common adverse reactions (Grades 1 to 4) observed in ≥ 2% of clinical trial participants receiving Cabenuva were injection site reactions, pyrexia, fatigue, headache, musculoskeletal pain, nausea, sleep disorders, dizziness and rash. Serious adverse events occurred in 4% (24/591) of patients taking Cabenuva, and 3% (17/591) of adverse events led to withdrawal.

Cabenuva was preferred by nine out of 10 patients over their previous daily oral therapy in these pivotal studies. Patient preference data was collected from clinical trial participants who received Cabenuva.

In a pooled exploratory analysis of this Intent-to-Treat Exposed (ITT-E) population, 532 patients completed a single-item question at Week 48 (59 patients did not) and 88% (523/591) preferred Cabenuva compared with 2% (9/591) who preferred their previous ARV treatment.

The results were descriptive in nature and are not intended to imply clinical significance.

To support the successful delivery of the once-monthly regimen to people living with HIV (PLHIV), ViiV Healthcare sponsored the CUSTOMIZE trial, the first-ever, pre-approval implementation science study to identify and evaluate approaches to integrate Cabenuva into clinical practices in the US.

Interim findings presented at AIDS2020 demonstrated that at four months, the majority of clinical staff participants continued to perceive the implementation of Cabenuva as highly acceptable, feasible and appropriate for PLHIV, and clinical staff had a substantial decrease in what they thought would be barriers to implementation of the injectable regimen.

ViiV Healthcare will begin shipping Cabenuva to wholesalers and specialty distributors in the US in February 2021.

The New Drug Application for Vocabria (cabotegravir) 30 milligram oral tablets was also approved by the FDA.

Vocabria is indicated, in combination with rilpivirine tablets, as a complete regimen for short-term treatment of HIV-1 infection in adults who are virologically stable and suppressed (HIV-1 RNA less than 50 copies/mL) on a stable ARV regimen with no history of treatment failure and with no known or suspected resistance to either cabotegravir or rilpivirine, for use as an oral lead-in to assess tolerability of cabotegravir prior to initiating Cabenuva and as an oral therapy for patients who will miss planned injection dosing of Cabenuva.

Cabenuva is indicated as a complete regimen for the treatment of HIV-1 infection in adults who are virologically suppressed (HIV-1 RNA less than 50 copies per milliliter [mL]) on a stable regimen, with no history of treatment failure, and with no known or suspected resistance to either cabotegravir or rilpivirine.

Cabenuva is administered as two intramuscular injections (cabotegravir and rilpivirine) in the buttocks during the same visit at a specialist clinic by a healthcare professional.

The complete regimen combines the integrase strand transfer inhibitor (INSTI) cabotegravir, developed by ViiV Healthcare, with rilpivirine, a non-nucleoside reverse transcriptase inhibitor (NNRTI) developed by Janssen Sciences Ireland UC, one of the Janssen Pharmaceutical Companies of Johnson and Johnson.

Rilpivirine is approved in the US as a 25mg tablet taken once-a-day for the treatment of HIV-1 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.

INSTIs, like cabotegravir, inhibit HIV replication by preventing the viral DNA from integrating into the genetic material of human immune cells (T-cells).

This step is essential in the HIV replication cycle and is also responsible for establishing chronic infection.

Rilpivirine is an NNRTI that works by interfering with an enzyme called reverse transcriptase, which in turn stops the virus from multiplying.