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Sourced From Drugbank

Lenacapavir Once-Yearly

Developer(s)

Gilead Sciences, Inc.

Originator
https://www.gilead.com/

United States

Gilead Sciences, Inc. is a multinational biopharmaceutical company that develops and manufactures innovative medicines for life-threatening diseases, including anti-viral therapeutics for HIV/AIDS, Hepatitis B, Hepatitis C and Covid-19. Headquartered in Foster City, California, Gilead was originally founded in 1987 and is currently listed on both the S&P 500 and the NASDAQ Biotechnology Index.

Drug structure

Lenacapavir Chemical Structure

Lenacapavir Chemical Structure

Sourced From Drugbank

Drug information

Associated long-acting platforms

Aqueous Solution

Administration route

Intramuscular

Therapeutic area(s)

HIV

Use case(s)

Pre-Exposure Prophylaxis (PrEP)
Prevention

Use of drug

Ease of administration

Administered by a community health worker
Administered by a nurse
Administered by a specialty health worker
To be determined

Frequency of administration

Yearly

User acceptance

to be determined

Dosage

Available dose and strength

3000 mg - 2x3mL intramuscular injections

Maximum dose

5000 mg - 2x5mL intramuscular injections

Recommended dosing regimen

Oral LEN 600 mg on Day 1 (with the IM injections) and Day 2 (The once‑yearly modality uses two investigational intramuscular (IM) formulations, distinct from the subcutaneous (SC) formulation used for twice‑yearly dosing)

Additional comments

Once-yearly intramuscular lenacapavir (5000 mg) provided higher Ctrough levels than the twice-yearly subcutaneous formulation. Future development suggests a lower optimal dose for the intramuscular option. A significant difference in the Phase I trial was the absence of oral loading doses for the once-yearly intramuscular formulation, which were required for the twice-yearly subcutaneous version due to its slow initial release. The intramuscular formulation also exhibited a faster initial increase in lenacapavir blood plasma concentration.

Dosage link(s)

Not provided

Drug information

Drug's link(s)

https://go.drugbank.com/drugs/DB15673

Generic name

Lenacapavir Once-Yearly

Brand name

Investigational

Compound type

Small molecule

Drug class/category

Capsid inhibitor

Summary

Once yearly lenacapavir (LEN) is an investigational intramuscular injectable formulation currently in clinical development for potential once-yearly HIV pre-exposure prophylaxis (PrEP). A phase I trial evaluating two once-yearly formulations found that a single 5000 mg intramuscular dose of lenacapavir resulted in sustained median plasma concentrations above those of the twice-yearly subcutaneous formulation (927 mg) for at least 56 weeks. Notably, the median concentrations at weeks 52 and 56 for the intramuscular formulations (50.7-65.6 ng/mL) were higher than the median concentration at week 26 (23.4 ng/mL) observed in PURPOSE 1 and 2. Once-yearly intramuscular lenacapavir may therefore further improve PrEP adherence, persistence, and scalability by offering reduced dosing frequency.

Approval status

Formulation is currently in clinical development and not yet approved in any jurisdiction. The direct progression to phase 3 for once‑yearly IM lenacapavir is justified scientifically and accepted by regulators because phase 1 data showed plasma exposures (and safety) that matched or exceeded the pivotal efficacy PK thresholds for the approved twice‑yearly SC regimen. Annual IM depot’s PK tail and implementation differences, unaddressed by PK bridging alone, will require real-world post-marketing/surveillance.

Regulatory authorities

Formulation is currently in clinical development and not yet approved in any jurisdiction. Once-yearly intramuscular LEN maintained plasma concentrations higher than those associated with efficacy for twice-yearly subcutaneous LEN for PrEP for >12 months (plasma exposures at one year exceeded levels associated with protection in PURPOSE trials). Both yearly investigational formulations were safe and tolerable. Results from phase 1 support moving to Phase 3 study for once-yearly IM LEN for HIV PrEP. WHO guideline refers to offering long‑acting injectable PrEP options as part of combination approaches, explicitly accepting PK/efficacy bridging for schedule changes and new depot products, provided safety and concentration requirements are met.

Delivery device(s)

No delivery device

Scale-up and manufacturing prospects

Scale-up prospects

LEN is already being manufactured at scale by Gilead for the twice-yearly SC product. For yearly IM, similar industrial processes will form the basis but with adaptations to the higher concentration and altered vehicle (ethanol content for IM depot). Equipment for injectable: Stainless steel pharmaceutical reactors, glass-lined reactors, rotary evaporator (rotovap), flash chromatography columns, stainless steel autoclave, cooling bath, silica gel chromatography columns, vacuum distillation apparatus, simulated moving bed chromatography system, Chiralpak columns.

Tentative equipment list for manufacturing

Storage of injectable lenacapavir in borosilicate vials is contraindicated due to issues with chemical compatibility. Instead, it is recommended that vials are made from aluminosilicate glass. High-precision mixing tanks with capability for viscous, ethanol-containing solutions. Aseptic filling/isolation units compatible with ethanol/PEG vehicles.Sterile filtration units for low-volume injectables.Standard lyophilisation (if relevant to final formulation.

Manufacturing

Vehicles with ethanol (often 5% or 10%) require specialised mixing times and solvent management to control viscosity and precipitation, which impact overall plant throughput and quality assurance. PEG and ethanol vehicles restrict direct steam sterilisation due to oxidation risk; sterile filtration is therefore preferred for terminal sterilisation—requiring high-quality, compatible filter assemblies with low extractable profiles.

Specific analytical instrument required for characterization of formulation

Proton nuclear magnetic resonance (1H NMR), High-performance liquid chromatography (HPLC), Ultra-Performance Liquid Chromatography (UPLC). Container closure integrity testers (for glass vials or prefilled syringes). Stability chambers for long-term and accelerated conditions.

Clinical trials

Pharmacokinetics and safety of once-yearly lenacapavir: a phase 1, open-label study

Identifier

Not provided

Link

https://doi.org/10.1016/S0140-6736(25)00405-2

Phase

Phase I

Status

Completed

Sponsor

Gilead Sciences Inc.

More details

Not provided

Purpose

Not provided

Interventions

Intervention 1

Once-yearly intramuscular lenacapavir formulation 1
Dosage: 5000 mg

Intervention 2

Once-yearly intramuscular lenacapavir formulation 2
Dosage: 5000 mg

Countries

Not provided

Sites / Institutions

Not provided

Trials dates

Anticipated Start Date
Not provided

Actual Start Date
Not provided

Anticipated Date of Last Follow-up
Not provided

Estimated Primary Completion Date
Not provided

Estimated Completion Date
Not provided

Actual Primary Completion Date
Not provided

Actual Completion Date
Not provided

Studied populations

Age Cohort

Genders

Accepts pregnant individuals
Unspecified

Accepts lactating individuals
Unspecified

Accepts healthy individuals
Yes

Comments about the studied populations

Not provided

Health status

Not provided

Study type

Interventional (clinical trial)

Enrollment

40

Allocation

Not provided

Intervention model

Parallel Assignment

Intervention model description

Not provided

Masking

Not provided

Masking description

Not provided

Frequency of administration

Yearly

Studied LA-formulation(s)

Injectable

Studied route(s) of administration

Intramuscular

Use case

PrEP

Key resources

Type Title Content Link
Link Pharmacokinetics and safety of once-yearly lenacapavir: a phase 1, open-label study https://doi.org/10.1016/S0140-6736(25)00405-2

PURPOSE 365

Identifier

NCT07047716

Link

https://clinicaltrials.gov/study/NCT07047716

Phase

Phase III

Status

Recruiting

Sponsor

Gilead Sciences

More details

The goal of this clinical study is to learn more about the study drug lenacapavir (LEN), safety, tolerability, and pharmacokinetics (how LEN is absorbed, modified, distributed, and removed from the body of the participants) of once-yearly intramuscular for HIV pre-exposure prophylaxis (PrEP) in people with an indication for PrEP. The primary objective of this study is to evaluate the pharmacokinetics (PK) and the safety and tolerability of intramuscular (IM) every 12 months (Q12M) LEN for PrEP among people with an indication for PrEP.

Purpose

Study of Lenacapavir as a Once-Yearly Injection for HIV Pre-exposure Prophylaxis (PrEP)

Interventions

Intervention 1

LEN 3000 mg injection once on Day 1 Oral LEN 600 mg on Day 1 and Day 2

Countries

United States of America

Sites / Institutions

Not provided

Trials dates

Anticipated Start Date
2025-07-01

Actual Start Date
2025-07-22

Anticipated Date of Last Follow-up
2026-03-02

Estimated Primary Completion Date
2028-09-01

Estimated Completion Date
2028-09-01

Actual Primary Completion Date
Not provided

Actual Completion Date
Not provided

Studied populations

Age Cohort

Genders

Accepts pregnant individuals
Yes

Accepts lactating individuals
Yes

Accepts healthy individuals
Yes

Comments about the studied populations

Key Inclusion Criteria: * At least 16 years of age at screening. * Receptive anal or vaginal sex in the past 6 months and at least 1 of the following: 1. Condomless receptive sex (vaginal or anal) with 1 or more sex partners of unknown HIV status during the past 6 months 2. For a person who has engaged in anal sex in the past 6 months: diagnosis of syphilis, gonorrhea, or chlamydia in the past 6 months 3. For a person who has engaged in vaginal sex in the past 6 months: diagnosis of syphilis or gonorrhea in the past 6 months 4. Sex with partner known to be living with HIV with an unknown or detectable viral load in the past 6 months * Negative local rapid fourth generation HIV-1/2 antibody (Ab)/antigen (Ag) test, central fourth generation HIV-1/2 Ab/Ag, and HIV-1 RNA quantitative

Health status

Negative to : HBV, HCV, HIV

Study type

Interventional (clinical trial)

Enrollment

350

Allocation

Not provided

Intervention model

Single group assignment

Intervention model description

Not provided

Masking

Open label

Masking description

Not provided

Frequency of administration

Yearly

Studied LA-formulation(s)

Injectable
Tablet

Studied route(s) of administration

Intramuscular

Use case

PrEP

Key resources

Type Title Content Link
Link First Clinical Data for Gilead’s Investigational Once-Yearly Lenacapavir for HIV Prevention Presented at CROI 2025 and Published in The Lancet https://www.gilead.com/news/news-details/2025/first-clinical-data-for-gileads-investigational-once-yearly-lenacapavir-for-hiv-prevention-presented-at-croi-2025-and-published-in-the-lancet
Publication Pharmacokinetics and safety of once-yearly lenacapavir: a phase 1, open-label study. Jogiraju, Vamshi et al. The Lancet, Volume 405, Issue 10485, 1147 - 1154 BackgroundLong-acting antiretrovirals can address barriers to HIV pre-exposure prophylaxis (PrEP), such as stigma and adherence. In two phase 3 trials, twice-yearly subcutaneous lenacapavir was safe and highly efficacious for PrEP in diverse populations. Furthering long-acting PrEP efforts, this study assessed the pharmacokinetics and safety of two once-yearly intramuscular lenacapavir formulations.MethodsThis phase 1, open-label study in participants aged 18–55 years without HIV evaluated the pharmacokinetics, safety, and tolerability of two lenacapavir free acid formulations administered by ventrogluteal intramuscular injection as a single 5000 mg dose (formulation 1 with 5% w/w ethanol, formulation 2 with 10% w/w ethanol). Pharmacokinetic samples were collected at prespecified timepoints up to 56 weeks. Lenacapavir plasma concentrations were measured with a validated liquid chromatography–tandem mass spectrometry method and summarised with non-compartmental analysis. Pharmacokinetic parameters evaluated included the area under the concentration–time curve for the once-yearly dosing interval calculated from days 1 to 365 (AUCdays 1–365), peak plasma concentration, time to reach peak plasma concentration, and trough concentration (Ctrough). Plasma concentration data from phase 3 studies of twice-yearly subcutaneous lenacapavir (PURPOSE 1 and PURPOSE 2) were pooled for comparison with once-yearly intramuscular lenacapavir formulations. Safety and tolerability, including participant-reported pain scores, were assessed.Findings20 participants received lenacapavir formulation 1 and 20 received lenacapavir formulation 2. For estimation of pharmacokinetic parameters, sample size varied over time with at least 13 participants (formulation 1) and at least 19 participants (formulation 2) due to early discontinuations for reasons unrelated to the study drug. Following administration of intramuscular lenacapavir, concentrations increased rapidly, and median time to maximum concentration was 84·1 days (IQR 56·1–112·0) for formulation 1 and 69·9 days (55·3–105·5) for formulation 2. The highest median concentration of once-yearly intramuscular lenacapavir (247·0 ng/mL [IQR 184·0–346·0] for formulation 1, 336·0 ng/mL [233·5–474·3] for formulation 2) remained above the highest median twice-yearly subcutaneous lenacapavir concentration (67·3 ng/mL [46·8–91·4]). Median Ctrough at the end of 52 weeks for formulation 1 was 57·0 ng/mL (IQR 49·9–72·4) and for formulation 2 was 65·6 ng/mL (41·8–87·1), exceeding the median twice-yearly subcutaneous lenacapavir Ctrough of 23·4 ng/mL (15·7–34·3) at the end of 26 weeks. Median AUCdays 1–365 for formulation 1 was 1011·1 h*μg/mL (IQR 881·0–1490·2) and for formulation 2 was 1274·0 h*μg/mL (1177·3–1704·8). Adverse events were mostly grade 1 or 2. The most common was injection-site pain (16 [80%] participants given formulation 1, 15 [75%] given formulation 2), which was generally mild, resolved within 1 week, and was substantially reduced by pretreatment with ice.InterpretationFollowing administration of once-yearly intramuscular lenacapavir, median plasma concentrations exceeded those associated with efficacy in phase 3 studies of twice-yearly subcutaneous lenacapavir for PrEP for at least 56 weeks. Both formulations were safe and well tolerated. These data show the potential for biomedical HIV prevention with a once-yearly dosing interval.
Link Pharmacokinetics and Safety of Once-Yearly Lenacapavir - CROI2025 https://www.askgileadmedical.com/docs/conference/Jogiraju_CROI2025_oral_LEN%20Q12M@pdf
Link Pharmacokinetics and safety of once-yearly lenacapavir: a phase 1, open-label study https://doi.org/10.1016/S0140-6736(25)00405-2

Excipients

Proprietary excipients used

Not provided

Novel excipients or existing excipients at a concentration above Inactive Ingredients Database (IID) for the specified route of administration

Not provided

Residual solvents used

Not provided

Patent info

Formulation patent families

Patent informations
Patent description Representative patent Categories Patent holder Licence with MPP Patent source
Dosing regimen of lenacapavir for treatment/prevention of HIV (oral or SC) Q26 weeks
Expiry date: 2044-04-18
The present disclosure relates to dosing regimens of an HIV capsid inhibitor and methods for the treatment or prevention of a human immunodeficiency virus (HIV) infection in a patient. 		WO2024220624 Dose/Regimen Gilead Sciences, Inc No
Patent status
Patent status/countries Low, Low- middle and upper-middle High income
Granted
Filed Argentina Taiwan, Province of China, United States of America, Australia
Not in force World Intellectual Property Organization (WIPO) World Intellectual Property Organization (WIPO)
Patent informations
Patent description Representative patent Categories Patent holder Licence with MPP Patent source
Dosing regimen of lenacapavir for treatment/prevention of HIV (oral or SC) Q26 weeks including bridging dosage
Expiry date: 2043-08-23
The present disclosure relates to dosing regimens of an HIV capsid inhibitor and methods for the treatment or prevention of a human immunodeficiency virus (HIV) infection in a patient. 		WO2025042394 Dose/Regimen Gilead Sciences, Inc No
Patent status
Patent status/countries Low, Low- middle and upper-middle High income
Granted
Filed World Intellectual Property Organization (WIPO) World Intellectual Property Organization (WIPO)
Not in force
Patent informations
Patent description Representative patent Categories Patent holder Licence with MPP Patent source
Lenacapavir use in HIV pre-exposure prophylaxis (PrEP)
Expiry date: 2040-11-25
The present disclosure provides methods of preventing HIV in a subject, comprising administering to the subject a therapeutically effective amount of compounds of Formula (la) or (lb) or a pharmaceutically acceptable salt thereof, optionally in combination with one or more additional therapeutic agents. Methods of reducing the risk of acquiring HIV (e.g, HIV-1 and/or HIV-2) are also provided. 		WO2021108544 Use Gilead Sciences, Inc No
Patent status
Patent status/countries Low, Low- middle and upper-middle High income
Granted Australia, United States of America
Filed China, Albania, Serbia, Türkiye, North Macedonia, India Australia, Canada, Liechtenstein, Italy, Norway, Malta, Denmark, Belgium, United Kingdom, Greece, Netherlands, Hungary, Croatia, Switzerland, Spain, San Marino, Slovenia, Austria, Romania, Iceland, Cyprus, Finland, France, Bulgaria, Slovakia, Poland, Latvia, Ireland, Estonia, Germany, Luxembourg, Portugal, Czechia, Lithuania, Monaco, Sweden, Taiwan, Province of China, United States of America, Hong Kong
Not in force World Intellectual Property Organization (WIPO), Morocco, Tunisia, Bosnia and Herzegovina, Cambodia, Montenegro, Moldova, Republic of World Intellectual Property Organization (WIPO), Japan, Korea, Republic of, United States of America
Patent informations
Patent description Representative patent Categories Patent holder Licence with MPP Patent source
Lenacapavir use to treat multidrug resistant HIV infection in heavily treatment-experienced
Expiry date: 2039-07-15
The present disclosure relates to compounds of Formula (Ia) and (Ib) or a pharmaceutically acceptable salt thereof, which are useful in the treatment of an HIV infection in heavily treatment-experienced patients with multidrug resistant HIV infection. 		WO2020018459 Use Gilead Sciences, Inc No
Patent status
Patent status/countries Low, Low- middle and upper-middle High income
Granted Australia, United States of America
Filed China, Albania, Serbia, Türkiye, North Macedonia Australia, Canada, Liechtenstein, Italy, Norway, Malta, Denmark, Belgium, United Kingdom, Greece, Netherlands, Hungary, Croatia, Switzerland, Spain, San Marino, Slovenia, Austria, Romania, Iceland, Cyprus, Finland, France, Bulgaria, Slovakia, Poland, Latvia, Ireland, Estonia, Germany, Luxembourg, Portugal, Czechia, Lithuania, Monaco, Sweden, Korea, Republic of, Taiwan, Province of China
Not in force World Intellectual Property Organization (WIPO), Morocco, Tunisia, Bosnia and Herzegovina, Cambodia, Montenegro, Moldova, Republic of World Intellectual Property Organization (WIPO), Australia, Canada, Japan, Korea, Republic of
Patent informations
Patent description Representative patent Categories Patent holder Licence with MPP Patent source
Lenacapavir manufacturing processess and intermediates
Expiry date: 2039-02-15
The present disclosure relates to methods and intermediates useful for preparing a compound of formula (I): (I) or a co-crystal, solvate, salt or combination thereof. 		WO2019161280 Intermediate(s), Process Gilead Sciences, Inc No
Patent status
Patent status/countries Low, Low- middle and upper-middle High income
Granted China, Türkiye, India Australia, Liechtenstein, Italy, Norway, Malta, Denmark, Belgium, United Kingdom, Greece, Netherlands, Switzerland, Spain, Slovenia, Austria, Finland, France, Bulgaria, Slovakia, Poland, Latvia, Ireland, Estonia, Germany, Luxembourg, Portugal, Czechia, Sweden, Japan, Korea, Republic of, Taiwan, Province of China, United States of America, Hong Kong
Filed China, Albania, Serbia, Türkiye, North Macedonia, India Australia, Canada, Liechtenstein, Italy, Norway, Malta, Denmark, Belgium, United Kingdom, Greece, Netherlands, Hungary, Croatia, Switzerland, Spain, San Marino, Slovenia, Austria, Romania, Iceland, Cyprus, Finland, France, Bulgaria, Slovakia, Poland, Latvia, Ireland, Estonia, Germany, Luxembourg, Portugal, Czechia, Lithuania, Monaco, Sweden, Japan, Korea, Republic of, Taiwan, Province of China, United States of America
Not in force World Intellectual Property Organization (WIPO), Argentina, Morocco, Tunisia, Albania, Serbia, Bosnia and Herzegovina, Cambodia, Montenegro, Moldova, Republic of, North Macedonia World Intellectual Property Organization (WIPO), Hungary, Croatia, San Marino, Romania, Iceland, Cyprus, Lithuania, Monaco, Bahamas
Patent informations
Patent description Representative patent Categories Patent holder Licence with MPP Patent source
Crystalline forms of Lenacapavir sodium salt
Expiry date: 2038-08-16
Lenacapavir solid forms, including pharmaceutically acceptable salts and cocrystals of the inhibitor, as well as crystalline forms of the salts and cocrystals, for use in the treatment of a Retroviridae viral infection including an infection caused by the HIV virus. The present disclosure also relates to pharmaceutical compositions containing the novel salts, cocrystals, and crystalline forms thereof, and methods of treating or preventing a Retroviridae viral infection. 		WO2019035904 Polymorphs Gilead Sciences, Inc No
Patent status
Patent status/countries Low, Low- middle and upper-middle High income
Granted Türkiye Belgium, Germany, France, Luxembourg, Netherlands, Switzerland, United Kingdom, Sweden, Italy, Austria, Liechtenstein, Greece, Spain, Denmark, Portugal, Ireland, Finland, Cyprus, Bulgaria, Czechia, Estonia, Slovakia, Poland, Malta, Norway, Romania, Latvia, Lithuania, Slovenia, Australia, Canada, Japan, Korea, Republic of, Taiwan, Province of China, United States of America, Hong Kong
Filed Türkiye, North Macedonia, Albania, Serbia, China, India Belgium, Germany, France, Luxembourg, Netherlands, Switzerland, United Kingdom, Sweden, Italy, Austria, Liechtenstein, Greece, Spain, Denmark, Monaco, Portugal, Ireland, Finland, Cyprus, Bulgaria, Czechia, Estonia, Slovakia, Hungary, Poland, Iceland, Malta, Norway, San Marino, Croatia, Romania, Latvia, Lithuania, Slovenia, Canada, Hong Kong
Not in force World Intellectual Property Organization (WIPO), North Macedonia, Albania, Bosnia and Herzegovina, Montenegro, Serbia, Moldova, Republic of, Morocco, Tunisia, Cambodia, Argentina, Bangladesh World Intellectual Property Organization (WIPO), Luxembourg, Denmark, Monaco, Finland, Cyprus, Bulgaria, Estonia, Hungary, Iceland, Malta, San Marino, Croatia, Romania, Latvia, Lithuania, Japan, Taiwan, Province of China
Patent informations
Patent description Representative patent Categories Patent holder Licence with MPP Patent source
Lenacapavir compound and its use in HIV (oral and parenteral)
Expiry date: 2037-08-17
The present disclosure relates to novel compounds for use in the treatment of a Retroviridae viral infection including an infection caused by the HIV virus. The present disclosure also relates to intermediates for its preparation and to pharmaceutical compositions containing said novel compound. 		WO2018035359 Compound Gilead Sciences, Inc No
Patent status
Patent status/countries Low, Low- middle and upper-middle High income
Granted Türkiye, Morocco, Brazil, China, Colombia, Dominican Republic, Turkmenistan, Belarus, Tajikistan, Kazakhstan, Azerbaijan, Kyrgyzstan, Armenia, Mexico, Peru, Philippines, Botswana, Gambia (the), Ghana, Kenya, Lesotho, Malawi, Mozambique, Namibia, Sierra Leone, Liberia, Sao Tome and Principe, Sudan, Eswatini, Tanzania, United Republic of, Zambia, Zimbabwe, Indonesia, Malaysia, Ukraine, South Africa, Uzbekistan Belgium, Germany, France, Luxembourg, Netherlands, Switzerland, United Kingdom, Sweden, Italy, Austria, Liechtenstein, Greece, Spain, Denmark, Portugal, Ireland, Finland, Cyprus, Bulgaria, Czechia, Estonia, Slovakia, Hungary, Poland, Iceland, Malta, Norway, Croatia, Romania, Latvia, Lithuania, Slovenia, Australia, Canada, Costa Rica, Russian Federation, Hong Kong, Israel, Japan, Korea, Republic of, New Zealand, Singapore, Taiwan, Province of China, United States of America, Bahamas, Bahrain, Kuwait, Qatar, Saudi Arabia, Oman, United Arab Emirates, Macao, Panama
Filed Türkiye, North Macedonia, Albania, Serbia, Morocco, Argentina, China, Jordan, Philippines, India, Uganda, Egypt, Guatemala, Indonesia, Nigeria, Thailand, Ukraine, Viet Nam Belgium, Germany, France, Luxembourg, Netherlands, Switzerland, United Kingdom, Sweden, Italy, Austria, Liechtenstein, Greece, Spain, Denmark, Monaco, Portugal, Ireland, Finland, Cyprus, Bulgaria, Czechia, Estonia, Slovakia, Hungary, Poland, Iceland, Malta, Norway, San Marino, Croatia, Romania, Latvia, Lithuania, Slovenia, Australia, Hong Kong, Korea, Republic of, Singapore, Taiwan, Province of China, United States of America, Saudi Arabia, Panama
Not in force World Intellectual Property Organization (WIPO), North Macedonia, Albania, Bosnia and Herzegovina, Montenegro, Serbia, Moldova, Republic of, Morocco, Argentina, Colombia, Dominican Republic, Ecuador, Peru, Rwanda, Uganda, Bangladesh, Bolivia (Plurinational State of), Cuba, Egypt, Benin, Cameroon, Burkina Faso, Chad, Guinea-Bissau, Comoros, Mali, Senegal, Congo, Guinea, Gabon, Niger, Equatorial Guinea, Mauritania, Togo, Côte d'Ivoire, Central African Republic, Pakistan, Paraguay, El Salvador, Venezuela (Bolivarian Republic of) World Intellectual Property Organization (WIPO), Monaco, Malta, San Marino, Chile, Japan, Korea, Republic of, Uruguay, Trinidad and Tobago
Patent informations
Patent description Representative patent Categories Patent holder Licence with MPP Patent source
Lenacapavir and analogues (Markush formula) and their use in HIV
Expiry date: 2034-02-28
Compounds of formula (I) or salts thereof are disclosed. Also disclosed are pharmaceutical compositions comprising a compound of formula I, processes for preparing compounds of formula I, intermediates useful for preparing compounds of formula I and therapeutic methods for treating a Retroviridae viral infection including an infection caused by the HIV virus. 		WO2014134566 Compound Gilead Sciences, Inc No
Patent status
Patent status/countries Low, Low- middle and upper-middle High income
Granted Türkiye, North Macedonia, Albania, Bosnia and Herzegovina, Montenegro, Serbia, Brazil, China, Cuba, Turkmenistan, Belarus, Tajikistan, Kazakhstan, Azerbaijan, Kyrgyzstan, Armenia, Mexico, Peru, Philippines, Ukraine, Botswana, Gambia (the), Ghana, Kenya, Lesotho, Malawi, Mozambique, Namibia, Sierra Leone, Liberia, Rwanda, Sudan, Eswatini, Tanzania, United Republic of, Zambia, Zimbabwe, Benin, Cameroon, Burkina Faso, Chad, Guinea-Bissau, Comoros, Mali, Senegal, Congo, Guinea, Gabon, Niger, Equatorial Guinea, Mauritania, Togo, Côte d'Ivoire, Central African Republic, Colombia, Indonesia, Malaysia, Viet Nam, South Africa Belgium, Germany, France, Luxembourg, Netherlands, Switzerland, United Kingdom, Sweden, Italy, Austria, Liechtenstein, Greece, Spain, Denmark, Monaco, Portugal, Ireland, Finland, Cyprus, Bulgaria, Czechia, Estonia, Slovakia, Hungary, Poland, Iceland, Malta, Norway, San Marino, Croatia, Romania, Latvia, Lithuania, Slovenia, Australia, Canada, Chile, Costa Rica, Russian Federation, Hong Kong, Israel, Japan, Korea, Republic of, New Zealand, Singapore, Taiwan, Province of China, United States of America, Bahrain, Kuwait, Qatar, Saudi Arabia, Oman, United Arab Emirates, Macao, Panama
Filed Türkiye, North Macedonia, Albania, Serbia, Argentina, Ukraine, India, Egypt, Thailand Belgium, Germany, France, Luxembourg, Netherlands, Switzerland, United Kingdom, Sweden, Italy, Austria, Liechtenstein, Greece, Spain, Denmark, Monaco, Portugal, Ireland, Finland, Cyprus, Bulgaria, Czechia, Estonia, Slovakia, Hungary, Poland, Iceland, Malta, Norway, San Marino, Croatia, Romania, Latvia, Lithuania, Slovenia, United States of America
Not in force World Intellectual Property Organization (WIPO), North Macedonia, Albania, Bosnia and Herzegovina, Montenegro, Serbia, Argentina, Brazil, China, Moldova, Republic of, Peru, Uganda, Bolivia (Plurinational State of), Colombia, Ecuador, Malaysia, Paraguay, Pakistan, El Salvador, Venezuela (Bolivarian Republic of), Viet Nam, South Africa World Intellectual Property Organization (WIPO), Luxembourg, Denmark, Monaco, Finland, Cyprus, Bulgaria, Estonia, Malta, San Marino, Croatia, Romania, Latvia, Lithuania, Australia, Canada, Costa Rica, Hong Kong, Japan, New Zealand, Singapore, United States of America, Uruguay, Bahamas

Supporting material

Publications

Pharmacokinetics and safety of once-yearly lenacapavir: a phase 1, open-label study. Jogiraju, Vamshi et al. The Lancet, Volume 405, Issue 10485, 1147 - 1154

Background

Long-acting antiretrovirals can address barriers to HIV pre-exposure prophylaxis (PrEP), such as stigma and adherence. In two phase 3 trials, twice-yearly subcutaneous lenacapavir was safe and highly efficacious for PrEP in diverse populations. Furthering long-acting PrEP efforts, this study assessed the pharmacokinetics and safety of two once-yearly intramuscular lenacapavir formulations.

Methods

This phase 1, open-label study in participants aged 18–55 years without HIV evaluated the pharmacokinetics, safety, and tolerability of two lenacapavir free acid formulations administered by ventrogluteal intramuscular injection as a single 5000 mg dose (formulation 1 with 5% w/w ethanol, formulation 2 with 10% w/w ethanol). Pharmacokinetic samples were collected at prespecified timepoints up to 56 weeks. Lenacapavir plasma concentrations were measured with a validated liquid chromatography–tandem mass spectrometry method and summarised with non-compartmental analysis. Pharmacokinetic parameters evaluated included the area under the concentration–time curve for the once-yearly dosing interval calculated from days 1 to 365 (AUCdays 1–365), peak plasma concentration, time to reach peak plasma concentration, and trough concentration (Ctrough). Plasma concentration data from phase 3 studies of twice-yearly subcutaneous lenacapavir (PURPOSE 1 and PURPOSE 2) were pooled for comparison with once-yearly intramuscular lenacapavir formulations. Safety and tolerability, including participant-reported pain scores, were assessed.

Findings

20 participants received lenacapavir formulation 1 and 20 received lenacapavir formulation 2. For estimation of pharmacokinetic parameters, sample size varied over time with at least 13 participants (formulation 1) and at least 19 participants (formulation 2) due to early discontinuations for reasons unrelated to the study drug. Following administration of intramuscular lenacapavir, concentrations increased rapidly, and median time to maximum concentration was 84·1 days (IQR 56·1–112·0) for formulation 1 and 69·9 days (55·3–105·5) for formulation 2. The highest median concentration of once-yearly intramuscular lenacapavir (247·0 ng/mL [IQR 184·0–346·0] for formulation 1, 336·0 ng/mL [233·5–474·3] for formulation 2) remained above the highest median twice-yearly subcutaneous lenacapavir concentration (67·3 ng/mL [46·8–91·4]). Median Ctrough at the end of 52 weeks for formulation 1 was 57·0 ng/mL (IQR 49·9–72·4) and for formulation 2 was 65·6 ng/mL (41·8–87·1), exceeding the median twice-yearly subcutaneous lenacapavir Ctrough of 23·4 ng/mL (15·7–34·3) at the end of 26 weeks. Median AUCdays 1–365 for formulation 1 was 1011·1 h*μg/mL (IQR 881·0–1490·2) and for formulation 2 was 1274·0 h*μg/mL (1177·3–1704·8). Adverse events were mostly grade 1 or 2. The most common was injection-site pain (16 [80%] participants given formulation 1, 15 [75%] given formulation 2), which was generally mild, resolved within 1 week, and was substantially reduced by pretreatment with ice.

Interpretation

Following administration of once-yearly intramuscular lenacapavir, median plasma concentrations exceeded those associated with efficacy in phase 3 studies of twice-yearly subcutaneous lenacapavir for PrEP for at least 56 weeks. Both formulations were safe and well tolerated. These data show the potential for biomedical HIV prevention with a once-yearly dosing interval.

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