Capsid inhibitor GS-6207 (lenacapavir): potential for 6 monthly dosing for MDR HIV
13 December 2019. Related: Conference reports, Antiretrovirals, EACS 17 Basel 2019.
Simon Collins, HIV i-Base
Two studies at EACS 2019 included new information about the capsid inhibitor GS-6207 (lenacapavir).
This pipeline compound in early stages of development is important for having activity against HIV that is resistant to existing HIV drugs, high potency (with picomolar activity), being active at multiple stages of the viral lifecycle and having the potential for long-acting formulations for both treatment and prevention.
Rebecca Begley from Gilead Sciences reported the unblinded data from the first phase 1 PK and safety study in HIV negative participants. 
Although the virological results from this study were first presented at CROI 2019, the new analysis included additional safety data and modelled pharmacokinetics to predict likely dosing. [2, 3]
The most common side effects were injections site reactions (ISRs), reported in 19 (59%) participants receiving GS-6207 compared to in 2/8 (25%) of participants receiving placebo. These were all mild and mainly erythema (47%) or pain (38%) and resolved within a few days.
PK results showed that at the 100 mg, 300 mg and 450 mg doses, drug levels remained above the protein adjusted EC90 (3.89 ng/mL) at week 12, and was sustained out to week 24 in the two highest doses.
The second poster was from a similar randomised, placebo-controlled, dose-ranging phase 1b study in HIV positive participants. 
All participants receiving GS-6207 had at least 1 log copies/mL reduction (range: 1.16 to 2.86). Mean viral load reductions after 10 days monotherapy of –1.75, –1.76 and –2.20 in the 50 mg, 150 mg and 450 mg groups. At day 10 all participants started ART using bictegravir/FTC/TAF.
Although safety results from this study are still blinded, tolerability was good, with mild ISR’s reported by 63% (15/24) of participants. There were no serious grade 3/4 laboratory abnormalities. Some of these results were previously presented as a late-breaker poster at IAS 2019. [5, 6]
The PK results have led to a phase 2 study in treatment-experienced participants that will use a modified formulation to enable 6-monthly injections. 
- Begley R et al. Safety and PK of subcutaneous GS-6207, a novel HIV‑1 capsid inhibitor. Oral abstract PS13/1.
- Collins S. Capsid inhibitor GS-6207 shows potential for 3-monthly injections, HTB: 29 March 2019.
- Sage JE et al. Safety and PK of subcutaneous GS-6207, a novel HIV-1 capsid inhibitor. Conference on Retroviruses and Opportunistic Infections (CROI), 4-7 March 2019, Seattle. Oral abstract 141.
- Daar E et al. Single doses of long-acting capsid inhibitor GS-6207 administered by subcutaneous injection are safe and efficacious in people living with HIV. EACS 2019. Poster abstract PE3/17.
- Collins S. First viral load results for capsid inhibitor GS-6207: mean –2.2 log reduction at day 10. HTB 24 July 2019.
- Daar ES et al. Safety and antiviral activity over 10 days following a single dose of subcutaneous GS-6207, a first-in-class, long-acting HIV capsid inhibitor in people living with HIV. 10th IAS Conference on HIV Science (IAS 2019), 21-24 July 2019, Mexico City. Late breaker poster abstract. LBPEB13.
- ClinicalTrials.gov. Study to evaluate the safety and efficacy of GS-6207 combination with an optimized background regimen in heavily treatment experienced participants living with HIV-1 infection with multidrug resistance.