Cabotegravir – the first and only long-acting injectable pre-exposure prophylaxis (PrEP) option proven superior to daily oral emtricitabine/tenofovir disoproxil fumarate in reducing HIV acquisition – has received a positive opinion from the EMA’s Committee for Medicinal Products for Human Use (CHMP).
Suitable for use in high-risk adults and adolescents weighing at least 35 kg to reduce the risk of sexually acquired HIV-1 in combination with safer sex practices, cabotegravir is an integrase strand transfer inhibitor, which prevents the HIV virus from integrating into the genetic material of human immune cells.
Developed by ViiV Healthcare, the CHMP positive opinion relates to the oral 30 mg tablet, which may be administered for approximately one month before initiating the first injection to assess the tolerability of the medicine, as well as the 600 mg prolonged-release injectable suspension.
The injection is administered six times per year by a healthcare professional and is initiated with a single 600 mg (3 ml) injection given one month apart for two consecutive months. After the second initiation injection, the recommended continuation injection dose is a single 600 mg (3 ml) injection every two months.
This represents an important step in the prevention of HIV, especially given the failure of a HIV vaccine earlier in 2023. Cabotegravir, which is sold under the brand name Apretude, has already been approved for use in the US, Australia, Zimbabwe, South Africa, Malawi, Botswana, and Brazil.
Kimberly Smith, head of research and development at ViiV Healthcare, said: ‘The expansion of prevention options is critical if we are to end the HIV epidemic. Long-acting options have the potential to play an important role in reducing challenges such as inconsistent adherence to taking daily pills, and stigma associated with oral PrEP use that can be faced by people who could benefit from PrEP.‘
She added: ‘With the CHMP positive opinion, we are hopeful that people in Europe will soon be able to benefit from greater choice.‘
The human immunodeficiency virus (HIV) remains one of the most important communicable diseases in Europe, with approximately 100,000 new diagnoses across the continent each year. Infection is associated with serious disease, persistently high treatment and care costs. Despite progress being made in the delivery of HIV treatment and prevention services, plus a continuous decline in the incidence of new cases, HIV still leads to a significant number of deaths and shortened life expectancy.
Cabotegravir clinical efficacy
The positive opinion for cabotegravir in Europe was based on the results of two randomised, double-blind, placebo-controlled trials. The first, HPTN 083, compared the long-acting injectable cabotegravir, given intramuscularly every eight weeks, with daily oral tenofovir disoproxil fumarate-emtricitabine for the prevention of HIV infection in at-risk cisgender men.
The primary end point was incident HIV infection, which was reduced by 76% in participants given cabotegravir (Hazard ratio, HR = 0.34, 95% CI 0.18 – 0.62).
The second trial, HPTN 084, compared the efficacy of injectable cabotegravir with daily oral tenofovir diphosphate plus emtricitabine for HIV prevention in uninfected women. This time, there was an even greater reduction in the risk of HIV infection in the cabotegravir group (HR = 0·12, 95% CI 0.05 – 0.31, p < 0.0001).
