Lenacapavir
A twice-yearly HIV prevention and treatment agent — three fluorine / boron key fragments supplied as a package
Lenacapavir — project profile
- Therapeutic area
- Antiviral (HIV-1)
- Mechanism
- HIV-1 capsid inhibitor acting at multiple stages of the viral lifecycle
- Commercial status
- Marketed (US · EU · both treatment and prevention indications)
- Originator
- Gilead Sciences
- Brand name
- Sunlenca / Yeztugo
Why this project, right now
Only publicly disclosed facts: regulatory approvals, clinical data, supply-chain moves
- ✓In June 2025 the FDA approved Yeztugo (lenacapavir) for HIV pre-exposure prophylaxis — the first and only twice-yearly PrEP option. In the Phase 3 PURPOSE 1 and PURPOSE 2 trials, ≥99.9% of participants who received it remained HIV negative.
- ✓The treatment indication (Sunlenca) was approved in the US in December 2022 and in the EU in August 2022; the EU added the PrEP indication in September 2025. Two indications running in parallel mean sustained, long-term demand for starting materials.
- ✓WHO issued implementation guidelines for twice-yearly lenacapavir as PrEP in July 2025, and Gilead has signed royalty-free voluntary licences with six generic manufacturers covering 120 low- and middle-income countries — a generic supply chain is taking shape, and intermediate demand scales with it.
- ✓The molecule combines a trifluoroethyl group, a gem-difluoro plus trifluoromethyl fused ring system and an alkynyl sulfone — a textbook showcase for fluorine chemistry and chiral fragment capability.
Public regulatory and clinical milestones
| Date | Event |
|---|---|
| 2022-08 | EU authorises Sunlenca for multidrug-resistant HIV-1 in adults |
| 2022-12 | FDA approves Sunlenca (treatment indication) |
| 2024-12 | Named 2024 Breakthrough of the Year by Science |
| 2025-06-18 | FDA approves Yeztugo for HIV PrEP — twice-yearly subcutaneous injection |
| 2025-07 | WHO issues implementation guidelines for twice-yearly lenacapavir as PrEP |
| 2025-09 | EU authorises the PrEP indication |
Key intermediate list
3 key intermediates
| CAS No. | Chemical name | Fragment role | Action |
|---|---|---|---|
| 2189684-53-3 | 4-Chloro-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-(2,2,2-trifluoroethyl)-1H-indazol-3-amine | Indazole boronate fragment (4-chloro / 3-amino / N-trifluoroethyl; Suzuki coupling donor) Process note：Boronate ester: moisture-controlled, cold-chain handling; watch protodeboronation impurity and residual palladium | |
| 1620056-83-8 | 2-((3bS,4aR)-5,5-difluoro-3-(trifluoromethyl)-3b,4,4a,5-tetrahydro-1H-cyclopropa[3,4]cyclopenta[1,2-c]pyrazol-1-yl)acetic acid | Chiral pyrazole acetic-acid fragment (gem-difluoro + trifluoromethyl cyclopropa-fused cyclopentane core) Process note：Two contiguous stereocentres on a polyfluorinated core — optical purity and isomer separation are the process crux | |
| 2189684-54-4 | tert-butyl (S)-(1-(3-bromo-6-(3-methyl-3-(methylsulfonyl)but-1-yn-1-yl)pyridin-2-yl)-2-(3,5-difluorophenyl)ethyl)carbamate | Chiral alkynyl sulfone pyridine fragment (Boc-protected amine, bromopyridine, 3,5-difluorophenyl) Process note：Contains an (S)-amine stereocentre and a terminal alkynyl sulfone — requires chiral control and alkyne stability studies |
How we support this project
All three fragments can be quoted as a package or taken individually; chiral and fluorinated routes are co-developed with partner plants
Impurity profiling (protodeboronation, defluorination, isomers) plus method development for chiral ee, residual solvents and elemental impurities
Registration support for the generic supply chain: DMF feasibility assessment, starting-material justification, stability study design
Common capabilitiesThe same delivery capability backs every campaign project
- ✓Route design and process development: hands-on scale-up experience with fluorinated, chiral, boronate and heterocyclic fragments at partner plants
- ✓Scale continuity: gram-scale validation → hundred-gram → kilogram → commercial, without a route change
- ✓Analytics: chiral ee, related substances, residual solvents, elemental impurities and genotoxic-impurity assessment to ICH conventions
- ✓Registration support: DMF feasibility assessment, starting-material justification, stability study design
- ✓Confidentiality: customer projects run under NDA; no cross-disclosure between plants and end customers
Supply scope and compliance note
Most of the target drugs above are originator products still under patent. The intermediates listed here are supplied for research use, and for markets where the patent has expired or a valid licence is in place. The buyer is responsible for confirming patent status and registration requirements in the target market and for the resulting compliance obligations. Third-party brand names and trademarks belong to their respective owners and are referenced here only as a technical cross-reference.
Intermediate lists (CAS and chemical names) are taken from the Division II 2026 Key Projects source sheet. Regulatory and clinical information comes from originator press releases and public FDA material. Fragment roles are neutral descriptions derived from the chemical structure and do not represent the originator patent route. Chinese drug names are common industry transliterations, not official registered names.
Data version 2026-09