Drug name
Last update: Aug 2026Lotivibart (N6LS) (VH3810109) (mAb)
Developer(s)
Drug information
Not provided
N6LS
Not provided
Biotherapeutic
bNAb targeting gp120 on HIV-1 virus envelope
N6LS (GSK3810109A; VH3810109) is a long-acting version of the broadly neutralising antibody (bNAb) N6 currently in clinical development for the treatment of HIV-1 infection. The crystallisable fragment domain of N6LS contains two site-directed mutagenesis substitutions at amino acid residues N434S and M428L to extend bNAb efficacy and half-life. In contrast to other bNAbs that target the HIV-1 CD4-binding site, N6LS has a unique binding method that places less importance on the highly variable gp120 V5 loop and instead concentrates on highly conserved regions of the HIV-1 envelope. This interaction process enables N6LS to avoid major resistance mutations resulting from alterations in the highly glycosylated V5 loop region, which act to reduce the efficacy of other VRC01-class antibodies.
Unknown
Unknown
Therapeutic area(s)
- HIV
- Treatment
Administration route
Intravenous, Subcutaneous
Associated long-acting platforms
Broadly Neutralising Monoclonal Antibody
Use of drug
- Administered by a nurse
- Administered by a specialty health worker
Not provided
Dosage
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Associated compounds, formulations and regimens
Not provided
Associated technologies
Not provided
Additional information
Developer(s)
ViiV Healthcare
ViiV Healthcare is a pharmaceutical company that specializes in the development of therapies for HIV infection. The company is headquartered in Brentford in the United Kingdom and was initially formed in November 2009 as a part of a joint venture between GlaxoSmithKline and Pfizer.
Drug structure
Scale-up and manufacturing prospects
Production scale up and manufacturing requirements for therapeutic monoclonal antibody products 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.
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. Protein A chromatography or other suitable affinity capture apparatus followed by two chromatographic polishing steps such as cation- and anion-exchange. Ultrafiltration membrane system to concentrate and formulate the final product.
Biological activity of bNAbs is highly dependent 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 including bioprocessing, purification, product delivery and storage. Considerations to increase formulation stability may include pH optimisation and the addition of suitable excipients (e.g. surfactants, stabilizers and buffers).
Formulation characterisation for single-entity bNAb production includes 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.
Excipients & delivery device(s)
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No delivery device
Safety, Efficacy and Evidence Summary
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N6LS combination with fostemsavir and temsavir
Relates to therapeutic methods or methods of treating, clearing, preventing or curing HIV infection. Provides a combination of at least one agent selected from the group consisting of: fostemsavir and temsavir, or a pharmaceutically acceptable salt thereof and a CD4 binding site (CD4bs) binding protein for the use in treatment of HIV and/or clearance of HIV infected cells.
WO2023114951
Combination
ViiV Healthcare
Not provided
December 16, 2042
Unknown - National phase deadline 17 June 2024
N6LS + Cabotegravir
The invention relates to a combination of cabotegravir or a pharmaceutically acceptable salt thereof and a gp120 binding protein. The invention also provides a method of treatment for HIV with the co-administration of a therapeutically effective amount of cabotegravir or a pharmaceutically acceptable salt thereof and a therapeutically effective amount of a gp120 binding protein.
WO2022125378
Combination
ViiV Healthcare
Not provided
December 3, 2041
Filed in EP
N6LS - Neutralising antibodies to GP120 and their use
Antibodies and antigen binding fragments that specifically bind to gp120 and neutralize HIV-1. Nucleic acids encoding these antibodies, vectors and host cells are also provided. Methods for detecting HIV-1 using these antibodies are disclosed. In addition, the use of these antibodies, antigen binding fragment, nucleic acids and vectors to prevent and/or treat an HIV-1 infection is disclosed.
WO2016154003
Active substance
US DHHS
Not provided
March 18, 2036
Granted in China, India, US, South Africa, Filed in Europe