Current status of the Gilead LA/ER Pipeline
Speaker: Martin Rhee, Executive Director in Clinical Development, Gilead
Gilead’s Capsid Inhibitor project has been ongoing for more than 15 years.
- LEN is the foundation of the LA portfolio
- high potency (EC50=100pM), multi-modal mechanism, no overlapping resistance with existing agents, excellent PK with long half-life, flexible dosing profile (oral or SC).
- Used in combination for HIV Treatment and as monotherapy for HIV Prevention.
- Weekly oral (300 mg t1/2= 12d) and Q6M SC dosing (927mg t1/2= 7 to 11 weeks) are feasible.
Early clinical data show LEN is potent and highly efficacious in people with multi-drug resistant HIV.
- Phase 2/3 studies.
- Significant antiviral activity during the 14-day functional monotherapy period.
- 2 log10 decline in viral load (oral LEN + failing regimen).
- High rate of virologic suppression (VL<50c/mL) achieved and maintained during maintenance.
- 81% at 6 months and 78% at one year (LEN SC Q6M + OBR).
We are leveraging the efficacy and flexible LA profile of LEN to build a person-centric LA portfolio for HIV treatment.
- Studies of 2-drug regimens using oral and SC LEN (QD up to Q6M) in combination with diverse partner agents.
- Phase 2 study of oral LEN+ISL QW vs B/F/TAF QD in virologically suppressed PLWH.
- Restarted screening using a lower 2mg ISL dose per US FDA.
- Proof of concept study evaluating the first complete Q6M HIV treatment regimen – single-dose SC LEN + 2bNAbs (GS-5423 + GS-2872) in virologically suppressed PLWH.
- Data presented at CROI 2023.
- P2/3 study of oral LEN + BIC QD in PLWH with a history of treatment failure, known resistance to ≥ 1 class of drugs, and virologically suppressed on a complex regimen – potential as a simple, effective regimen in this population.
- Enrollment complete.
Phase 3 studies evaluating LA LEN for HIV PrEP.
- PURPOSE 1 actively screening in South Africa and Uganda (sites with sufficient background HIV [bHIV]).
- 5000 cis-gender adolescent girls and young women randomized 2:2:1 to LEN SC Q6M, oral F/TAF QD, and oral F/TDF QD (internal control)
- Primary endpoint is LEN vs bHIV and F/TAF vs bHIV at 52 weeks.
- PURPOSE 2 actively recruiting in the US, Peru, Brazil, and South Africa (sites with sufficient bHIV).
- 3000 cis-gender men, TGW, TGM, and gender non-binary individuals who have sex with men randomized 2:1 to LEN SC Q6M and oral F/TDF QD (internal control).
- Primary endpoint is LEN vs bHIV at 52 weeks.
Presentations at CROI 2023
- Eron J et al. Lenacapavir plus broadly neutralizing antibodies GS-5423 and GS-2872 for 6 monthly HIV-1 treatment
- Hagins D et al. CALIBRATE LA LEN as comb treatment in treatment-naïve PWH, week 80 results
- Obguabu O et al. CAPELLA LEN efficacy in heavily treatment experienced PWH at week 52.