The FINANCIAL — ViiV Healthcare, the global specialist HIV company majority owned by GSK, with Pfizer Inc. and Shionogi Limited as shareholders, on February 24 presented positive results from the 41 week phase IIa ECLAIR study, which evaluated the safety, tolerability, dosing and satisfaction with the investigational, long-acting, injectable cabotegravir as monotherapy for pre-exposure prophylaxis (PrEP) in HIV-uninfected healthy adult males not at high risk of acquiring HIV.1 Results were presented at the Conference on Retroviruses and Opportunistic Infections (CROI) in Boston.
Data from the study support the advancement of cabotegravir, an integrase strand transfer inhibitor, to the next stage of development as a potential drug for HIV prevention. Adverse events (AEs) during the injection phase occurred in 98% and 90% of cabotegravir and placebo group participants, respectively. Injection site pain was the most frequently reported Grade 2-4 AE for those receiving cabotegravir (59%, compared to 5% for placebo), according to GSK.
The ECLAIR study randomised 127 HIV-uninfected participants to cabotegravir or placebo (5:1) beginning with a safety assessment on oral cabotegravir (30mg) or matching placebo tablet for four weeks, followed by intramuscular injections of 800mg cabotegravir or placebo (sterile saline solution) dosed once every 12 weeks for three cycles.
A majority of participants in the study reported satisfaction with cabotegravir injections. Following repeat injections, 67/91 (74%) of participants favoured cabotegravir long-acting injections compared to oral cabotegravir.
“There are more than 36 million people worldwide living with HIV today and, despite considerable progress made in the fight against HIV, infections are still increasing in parts of the world. Preventative measures like PrEP could play an important role in reducing the number of new infections and help contribute to the goal of ending the global AIDS epidemic,” said John C Pottage, Jr, MD, Chief Scientific and Medical Officer, ViiV Healthcare. “We are encouraged by these first results from the ECLAIR study and look forward to understanding the potential efficacy and broader safety profile of cabotegravir in the PrEP setting as we move into phase III development later this year.”
The ECLAIR study also collected cabotegravir exposure data throughout each 12-week dosing interval. Results showed drug concentrations were lower than anticipated at the end of the dosing interval in approximately two-thirds of participants.1 As a result, an alternative dosing strategy of 600mg intramuscular injections every eight weeks is now under investigation as a means to optimise cabotegravir dosing prior to future safety and efficacy studies.
Adverse events in ECLAIR
Adverse events (AEs) leading to withdrawal during the oral phase (7/105) included three events of neutropenia, three events of increasing blood creatine phosphokinase (CPK) and one event of fatigue.1 For participants who entered the injection phase, a similar proportion (93% [87/94] for cabotegravir and 95% [20/21] for placebo) completed all three injection cycles.1 Self- reported injection intolerability led to withdrawal in 4% (4/94) of cabotegravir participants.1 One participant in the placebo group withdrew during the injection phase due to HIV seroconversion.
The number of Grade 2-4 AEs on the cabotegravir arm was higher compared to placebo during the injection phase (80% [75/94] for cabotegravir vs 48% [10/21] for placebo).1Grade 2 AEs in the injection phase not related to injection site pain included pyrexia (fever) (7% [7/94] for cabotegravir subjects and 0% for placebo subjects), injection site pruritus (itching) (6% [6/94] for cabotegravir subjects and 0% for placebo subjects) and injection site swelling (6% [6/94] for cabotegravir subjects and 0% for placebo subjects).1
Additional supporting data from the ECLAIR study on the satisfaction and acceptability of long-acting cabotegravir will be presented at CROI later today.