lenacapavir + teropavimab + zinlirvimab

Drug information

Delivery device(s)

Not provided

Scale-up prospects

LEN is commercially manufactured. Production scale up and manufacturing requirements for therapeutic mAbs are primarily related to formulation stability, pharmacokinetic suitability and maintenance of quality attributes. The industrial manufacture of high-concentration broadly neutralising antibody (bNAb) formulations for parenteral administration can introduce production challenges regarding aggregation propensity and formulation viscosity. Exploratory process optimisations such as bNAb co-formulation and multi-specific Ab composition have the potential to reduce overall manufacturing costs

Tentative equipment list for manufacturing

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. Industrial bioreactor vessel with a production volume capacity of between 5-25kL. Continuous disc stack centrifuges for bioreactor harvesting with subsequent membrane and depth filtration for supernatant clarification.

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. Biological activity of bNAbs is highly dependant on their chemical, conformational and structural stability. Reduced glycosylation of bNAbs during manufacture and chemical degradation processes such as deamidation can result in increased aggregation, loss of activity and diminished solubility. Degradation may occur at any stage throughout the manufacturing process.

Specific analytical instrument required for characterization of formulation

Proton nuclear magnetic resonance (1H NMR), High-performance liquid chromatography (HPLC), Ultra-Performance Liquid Chromatography (UPLC). Formulation characterisation for single-entity bNAb production include capillary isoelectric focusing and ion-exchange chromatography for identification of post-translational modifications, subvisible particle quantitation, thermal DSC, size-exclusion chromatography for measurement of concentration dependent aggregation rates and capillary electrophoresis for antibody fragmentation and clipping.

GS-US-536-5939

Identifier

NCT05729568

Link

https://clinicaltrials.gov/study/NCT05729568

Phase

Phase II

Status

Active, not recruiting

Sponsor

Gilead Sciences

More details

The goal of this study is to test the effectiveness, safety, and tolerability of the combination of broadly neutralizing antibodies (bNAbs) (teropavimab (TAB; GS-5423) and zinlirvimab (ZAB; GS-2872)) with lenacapavir (LEN) in virologically suppressed adults with HIV-1 infection. The purpose of this study is to evaluate the efficacy of switching to a regimen of LEN, TAB and ZAB, versus continuing on baseline oral antiretroviral therapy (ART) as determined by the proportion of participants with human immunodeficiency virus-1 (HIV-1) ribonucleic acid (RNA) ≥ 50 copies/mL at Week 26.

Purpose

A Study of Teropavimab and Zinlirvimab in Combination With Capsid Inhibitor Lenacapavir in Virologically Suppressed Adults With HIV-1 Infection

Interventions

Intervention 1

Intervention 2

Intervention 3

Intervention 4

Intervention 5

Countries

Sites / Institutions

Not provided

Trials dates

Anticipated Start Date
Not provided

Actual Start Date
2023-05-15

Anticipated Date of Last Follow-up
2025-06-26

Estimated Primary Completion Date
Not provided

Estimated Completion Date
2029-12-01

Actual Primary Completion Date
2024-07-02

Actual Completion Date
Not provided

Studied populations

Age Cohort

• Adults
• Older Adults

Genders

• All

Accepts pregnant individuals
Unspecified

Accepts lactating individuals
Unspecified

Accepts healthy individuals
No

Comments about the studied populations

Key Inclusion Criteria: * On stable oral antiretroviral therapy (ART) consisting of no more than 2 drug classes (with the exception of pharmacologic boosters cobicistat or ritonavir) for ≥ 1 year prior to screening visit 2. A change in ART regimen ≥ 28 days prior to screening visit 2 for reasons other than virologic failure (VF) (eg, tolerability, simplification, drug-drug interaction profile) is allowed. * No clinically significant documented historical resistance to the current ART regimen with the exception of isolated nucleoside reverse transcriptase inhibitor mutations including M184V or ≤ 2 thymidine analog mutations (TAMs: M41L, D67N, K70R, L210W, T215Y, and/or K219Q). * Plasma human immunodeficiency virus-1 (HIV-1) ribonucleic acid (RNA) \< 50 copies/mL at screening visit 2. * Doc

Health status

Study type

Interventional (clinical trial)

Enrollment

83

Allocation

Randomized

Intervention model

Parallel Assignment

Intervention model description

Not provided

Masking

Open label

Masking description

Not provided

Frequency of administration

Studied LA-formulation(s)

Studied route(s) of administration

Use case

Treatment

Key resources

GS-US-536-5816

Identifier

NCT04811040

Link

https://clinicaltrials.gov/study/NCT04811040

Phase

Phase I

Status

Completed

Sponsor

Gilead Sciences

More details

The primary objective of this study is to evaluate the safety and tolerability of a combination of the broadly neutralizing antibodies (bNAbs) teropavimab (formerly GS-5423) and zinlirvimab (formerly GS-2872) in combination with the HIV capsid inhibitor lenacapavir (LEN).

Purpose

Study to Evaluate the Safety and Efficacy of Teropavimab and Zinlirvimab in Combination With Lenacapavir in Virologically Suppressed Adults With HIV-1 Infection

Interventions

Not provided

Countries

Not provided

Sites / Institutions

Not provided

Trials dates

Anticipated Start Date
Not provided

Actual Start Date
2021-04-08

Anticipated Date of Last Follow-up
2024-12-19

Estimated Primary Completion Date
Not provided

Estimated Completion Date
Not provided

Actual Primary Completion Date
2022-06-09

Actual Completion Date
2023-10-26

Studied populations

Age Cohort

• Adults
• Older Adults

Genders

• All

Accepts pregnant individuals
Unspecified

Accepts lactating individuals
Unspecified

Accepts healthy individuals
No

Comments about the studied populations

Key Inclusion Criteria: * On first-line antiretroviral therapy (ART) for ≥ 2 years prior to screening. A change in ART regimen ≥ 28 days prior to screening for reasons other than virologic failure (VF) (eg, tolerability, simplification, drug-drug interaction profile) is allowed * No documented historical resistance to the current ART regimen * Plasma HIV-1 RNA \< 50 copies/mL at screening * Documented plasma HIV-1 RNA \< 50 copies/mL for ≥ 18 months preceding the screening visit (or undetectable HIV-1 RNA level according to the local assay being used if the limit of detection is ≥ 50 copies/mL). Unconfirmed virologic elevations of ≥ 50 copies/mL (transient detectable viremia, or "blip") prior to screening are acceptable. * Proviral phenotypic sensitivity to both teropavimab and zinlirvima

Health status

Not provided

Study type

Interventional (clinical trial)

Enrollment

32

Allocation

Randomized

Intervention model

Parallel Assignment

Intervention model description

Not provided

Masking

Double-blind masking

Masking description

Not provided

Frequency of administration

Not provided

Studied LA-formulation(s)

Not provided

Studied route(s) of administration

Not provided

Use case

Not provided

Key resources

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

Description

Lenacapavir, zinlirvimab and teropavimab combination and dosage form for treatment of HIV

Brief description

Provided are methods for administering long-acting anti-HIV broadly neutralizing antibodies twice annually, e.g., Q6M, Q24W, Q25W or Q26W.

Representative patent

WO2024044477

Category

Combination, Dosing Regimen, Method of Treatment

Patent holder

Gilead Sciences

Exclusivity

Not provided

Expiration date

August 11, 2043

Status

Granted: TW Pending: AU, CA, CN, EP, JP, LR, US

Publications

There are no publication

Additional documents

No documents were uploaded

Useful links

• Positive Proof-of-Concept Data for Investigational Combination Regimen of Lenacapavir with Broadly Neutralizing Antibodies as a Potential Twice-Yearly Approach for the Treatment of HIV

• Gilead Presents New HIV Treatment and Cure Research Data at CROI 2025, Including an Investigational Long-Acting, Twice-Yearly Therapy Option

	Collaborate for development Consider on a case by case basis, collaborating on developing long acting products with potential significant public health impact, especially for low- and middle-income countries (LMICs), utilising the referred to long-acting technology Not provided
	Share technical information for match-making assessment Provide necessary technical information to a potential partner, under confidentiality agreement, to enable preliminary assessment of whether specific medicines of public health importance in LMICs might be compatible with the referred to long-acting technology to achieve a public health benefit Not provided
	Work with MPP to expand access in LMICs In the event that a product using the referred to long-acting technology is successfully developed, the technology IP holder(s) will work with the Medicines Patent Pool towards putting in place the most appropriate strategy for timely and affordable access in low and middle-income countries, including through licensing Not provided

Not provided