A Phase 2b Multicenter, Randomized, Open-Label Study Comparing the Efficacy, Safety, PK, and Tolerability of VH3810109, Administered Either Intravenously Or As A Subcutaneous Infusion With rHuPH20, in Combination With CAB LA to Standard of Care in Virologically Suppressed Adults Living With HIV

The study aims at evaluating the efficacy of VH3810109, dosed in accordance with the dosing schedule as either intravenous (IV) infusion or subcutaneous (SC) infusion with recombinant hyaluronidase (rHuPH20), in combination with cabotegravir (CAB) intramuscular (IM) dosed in accordance with the dosing schedule in virologically suppressed, Antiretroviral therapy (ART)-experienced adult participants living with HIV.

Start Date17 Aug 2023

Sponsor / Collaborator

ViiV Healthcare Ltd.

NCT05291520

/ CompletedPhase 1

A Phase 1, Open-Label, Single-Dose Study of the Safety and Pharmacokinetics of a Human Monoclonal Antibody, GSK3810109, Administered Either Subcutaneously or Intravenously With Recombinant Human Hyaluronidase PH20 (rHuPH20) to Healthy Adults

An open-label, two part study to assess the safety, tolerability, and PK of VH3810109 in healthy adult participants. Participants will receive a single SC or IV dose of VH3810109 co-administered with rHuPH20 and will be followed up for 24 weeks.

Start Date23 Feb 2022

Sponsor / Collaborator

ViiV Healthcare Ltd.

NCT04871113

/ CompletedPhase 2

A Phase 2a Multicentre, Randomized, Open-Label, Two-Part Adaptive Design Study to Evaluate the Antiviral Effect, Safety and Tolerability of GSK3810109A, an HIV-1 Specific Broadly Neutralizing Human Monoclonal Antibody in Antiretroviral-naïve HIV-1-Infected Adults

This study is to evaluate antiviral activity, efficacy, safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of GSK3810109A in HIV-1 infected treatment naive adults. Participants will receive a single dose of GSK3810109A administered either intravenously (IV) or subcutaneously (SC). The study includes a screening phase, a randomized monotherapy phase and a standard of care follow-up phase.

Start Date22 Jun 2021

Sponsor / Collaborator

ViiV Healthcare Ltd.

100 Clinical Results associated with Iotivibart

100 Translational Medicine associated with Iotivibart

100 Patents (Medical) associated with Iotivibart

Literatures (Medical) associated with Iotivibart

31 Dec 2023·mAbs

Improved pharmacokinetics of HIV-neutralizing VRC01-class antibodies achieved by reduction of net positive charge on variable domain

Article

Author: Mascola, John R ; Shen, Chen-Hsiang ; Liu, Tracy ; Pegu, Amarendra ; Yang, Eun Sung ; Lusso, Paolo ; McKee, Krisha ; Kwong, Peter D ; Doria-Rose, Nicole A ; Rawi, Reda ; Reveiz, Mateo ; Liu, Qingbo ; Lin, Bob C ; Kwon, Young D ; Asokan, Mangaiarkarasi ; Schaub, Andrew J ; Bender, Michael F ; Louder, Mark K ; Zhang, Baoshan

The amino-acid composition of the immunoglobulin variable region has been observed to impact antibody pharmacokinetics (PK). Here, we sought to improve the PK of the broad HIV-1-neutralizing VRC01-class antibodies, VRC07-523LS and N6LS, by reducing the net positive charge in their variable domains. We used a structure-guided approach to generate a panel of antibody variants incorporating select Arg or Lys substituted to Asp, Gln, Glu, or Ser. The engineered variants exhibited reduced affinity to heparin, reduced polyreactivity, and improved PK in human FcRn-transgenic mice. One variant, VRC07-523LS.v34, with three charge substitutions, had an observed in vivo half-life and an estimated human half-life of 10.8 and 60 days, respectively (versus 5.4 and 38 days for VRC07-523LS) and retained functionality, neutralizing 92% of a 208-strain panel at a geometric mean IC₈₀ <1 µg/mL. Another variant, N6LS.C49, with two charge substitutions, had an observed in vivo half-life and an estimated human half-life of 14.5 and 80 days (versus 9.0 and 44 days for N6LS) and neutralized ~80% of 208 strains at a geometric mean IC₈₀ <1 µg/mL. Since Arg and Lys residues are prevalent in human antibodies, we propose substitution of select Arg or Lys with Asp, Gln, Glu, or Ser in the framework region as a general means to improve PK of therapeutic antibodies.

15 Aug 2017·Journal of VirologyQ2 · MEDICINE

Virological Control by the CD4-Binding Site Antibody N6 in Simian-Human Immunodeficiency Virus-Infected Rhesus Monkeys

Q2 · MEDICINE

Article

Author: Callow, Katherine ; Barouch, Dan H. ; Wang, Keyun ; Connors, Mark ; Chen, Xuejun ; Liu, Jinyan ; Chandrashekar, Abishek ; Huang, Jinghe ; Koup, Richard A. ; Mojta, Shanell ; Pegu, Amarendra ; Julg, Boris ; Abbink, Peter ; Mascola, John R. ; Molloy, Katherine ; Schmidt, Stephen D. ; Keele, Brandon F. ; Seaman, Michael S. ; Brinkman, Amanda

ABSTRACT Passive immunotherapy against HIV-1 will most likely require broadly neutralizing antibodies (bnAbs) with maximum breadth and potency to ensure therapeutic efficacy. Recently, the novel CD4 binding site antibody N6 demonstrated extraordinary neutralization breadth and potency against large panels of cross-clade pseudoviruses. We evaluated the in vivo antiviral activity of N6-LS, alone or in combination with the established V3-glycan antibody PGT121, in chronically simian-human immunodeficiency virus (SHIV)-SF162P3-infected macaques. A single dose of N6-LS suppressed plasma viral loads in 4 out of 5 animals at day 7, while the combination of both antibodies suppressed all animals. The combination of both antibodies had no additive antiviral effect compared to a single dose of PGT121, potentially reflecting the nearly 10-fold-higher potency of PGT121 against this SHIV. Viral rebound occurred in the majority of suppressed animals and was linked to declining plasma bnAb levels over time. In addition to the effect on plasma viremia, bnAb administration resulted in significantly reduced proviral DNA levels in PBMCs after 2 weeks and in lymph nodes after 10 weeks. Autologous neutralizing antibody (nAb) responses and CD8 + T-cell responses were not significantly enhanced in the bnAb-treated animals compared to control animals, arguing against their contribution to the viral effects observed. These results confirm the robust antiviral activity of N6-LS in vivo , supporting the further clinical development of this antibody. IMPORTANCE Monocloncal antibodies (MAbs) are being considered for passive immunotherapy of HIV-1 infection. A critical requirement for such strategies is the identification of MAbs that recognize the diversity of variants within circulating but also reservoir viruses, and MAb combinations might be needed to achieve this goal. This study evaluates the novel bnAb N6-LS alone or in combination with the bnAb PGT121, in rhesus macaques that were chronically infected with SHIV. The results demonstrate that N6-LS potently suppressed plasma viral loads in the majority of animals but that the combination with PGT121 was not superior to PGT121 alone in delaying time to viral rebound or reducing peripheral blood mononuclear cell (PBMC) or lymph node proviral DNA levels. The occurrence of viral escape variants in an N6-LS-monotreated animal, however, argues for the need to maximize breadth and antiviral efficacy by combining bnAbs for therapeutic indications.

PLOS PathogensQ1 · MEDICINE

TLR7 agonist, N6-LS and PGT121 delayed viral rebound in SHIV-infected macaques after antiretroviral therapy interruption

Q1 · MEDICINE

ArticleOA

Author: Robb, Merlin L ; Visudhiphan, Pornsuk ; Michael, Nelson L ; Koup, Richard A ; Vasan, Sandhya ; Silsorn, Decha ; Inthawong, Dutsadee ; Mascola, John R ; Imerbsin, Rawiwan ; Shi, Wei ; Chuenarom, Weerawan ; Barouch, Dan H ; Geleziunas, Romas ; Schuetz, Alexandra ; Sopanaporn, Jumpol ; Keawboon, Boot ; Pegu, Amarendra ; Hsu, Denise C

Toll-like receptor 7 (TLR7) agonist and PGT121 (broadly neutralizing antibody, bnAb) administration previously delayed viral rebound and induced SHIV remission. We evaluated the impact of GS-986 (TLR7 agonist) and dual bnAbs on viral rebound after antiretroviral therapy (ART) interruption. Rhesus macaques inoculated with SHIV-1157ipd3N4 were initiated on daily suppressive ART from Day 14 post SHIV inoculation. Active arm animals (n = 8) received GS-986, N6-LS and PGT121 after plasma viral suppression, starting from week 14. GS-986 induced immune activation and SHIV-specific T cell responses but not viral expression in all the active arm animals. After ART interruption, median time to viral rebound was 6 weeks in the active and 3 weeks in the control arm (p = 0.024). In this animal model, the administration of the combination of GS-986 and dual bnAbs was associated with a modest delay in viral rebound. This strategy should be further evaluated to better understand the underlying mechanisms for the induction of virus-specific immune responses and delay in viral rebound.

News (Medical) associated with Iotivibart

12 Mar 2025

·pipelinereview.com

ViiV Healthcare’s investigational broadly neutralising antibody - N6LS - successfully maintains viral suppression in long-acting treatment of HIV

LONDON, UK I March 12, 2025 I ViiV Healthcare, the global specialist HIV company majority owned by GSK, with Pfizer and Shionogi as shareholders, today announced positive findings from the company’s EMBRACE phase IIb study. 1 The study found that N6LS (VH3810109 or VH109), given every four months in combination with monthly cabotegravir long-acting (CAB LA), successfully kept viral levels suppressed in adults living with HIV who were already stable on treatment. It was also well tolerated by participants. These results were presented today at the Conference on Retroviruses and Opportunistic Infections (CROI 2025) in San Francisco, U.S. Kimberly Smith, M.D., MPH, Head of Research & Development at ViiV Healthcare, said :”As leaders in long-acting injectable innovation, we are building on the positive patient and physician experience we have with Cabenuva and pioneering the next generation of long-acting treatment options. The EMBRACE study demonstrated that VH109, a CD4-binding broadly neutralising antibody, administered every four months with cabotegravir, achieved high efficacy and was well tolerated through six months. We’re looking forward to continuing the development of VH109 as a component of our future ultra long-acting regimens.” Results from the EMBRACE study at the six-month primary endpoint showed that 96% of participants receiving VH109 60mg/kg intravenously (IV) and 88% receiving VH109 3000mg subcutaneously (SC) with rHuPH20 maintained HIV-1 RNA levels below 50 copies/mL, compared to 96% in the standard-of-care group. VH109 was administered in both arms every four months, combined with monthly CAB LA. Confirmed virologic failure was observed in two participants from each VH109 group. Overall, 4% of the IV group and 6% of the SC group had HIV-1 RNA levels of 50 copies/mL or higher, compared to none in the standard-of-care group when measured at month six. VH109 was generally well tolerated, though infusion site reactions were more frequent with SC administration, occurring in 14% compared to none with IV administration. Adverse events specific to the use of study medication were reported in 64% of the IV group and 65% of the SC group, with 16% of participants in the SC group experiencing grade 3-4 adverse events (erythema). No participants in the IV group experienced a grade 3-4 adverse event. Based on the favourable results seen in the trial, ViiV Healthcare will be progressing a six-month IV formulation of VH109 in combination with CAB LA for further evaluation in an EMBRACE part two trial. About Cabenuva (cabotegravir + rilpivirine) Cabenuva is indicated as a complete regimen for the treatment of HIV-1 infection in adults and adolescents 12 years and older and weighing at least 35kg to replace the current antiretroviral regimen in those who are virologically suppressed (HIV-1 RNA <50 c/ml) on a stable antiretroviral regimen with no history of treatment failure and with no known or suspected resistance to either cabotegravir or rilpivirine. The complete regimen combines the integrase strand transfer inhibitor (INSTI) cabotegravir, developed by ViiV Healthcare, with rilpivirine, a non-nucleoside reverse transcriptase inhibitor (NNRTI) developed by Janssen Sciences Ireland Unlimited Company. Rilpivirine tablets are approved in the U.S. and when used with cabotegravir is indicated for short-term treatment of HIV-1 infection in adults and adolescents 12 years and older and weighing at least 35kg who are virologically suppressed (HIV-1 RNA less than 50 copies/mL) on a stable regimen with no history of treatment failure and with no known or suspected resistance to either cabotegravir or rilpivirine. INSTIs inhibit HIV replication by preventing the viral DNA from integrating into the genetic material of human immune cells (T-cells). This step is essential in the HIV replication cycle and is also responsible for establishing chronic disease. Rilpivirine is an NNRTI that works by interfering with an enzyme called reverse transcriptase, which stops the virus from multiplying. Please consult the full Prescribing Information . Trademarks are owned by or licensed to the ViiV Healthcare group of companies. About ViiV Healthcare ViiV Healthcare is a global specialist HIV company established in November 2009 by GSK (LSE: GSK) and Pfizer (NYSE: PFE) dedicated to delivering advances in treatment and care for people living with HIV and for people who could benefit from HIV prevention. Shionogi became a ViiV shareholder in October 2012. The company’s aims are to take a deeper and broader interest in HIV and AIDS than any company has done before and take a new approach to deliver effective and innovative medicines for HIV treatment and prevention, as well as support communities affected by HIV. For more information on the company, its management, portfolio, pipeline, and commitment, please visit viivhealthcare.com. About GSK GSK is a global biopharma company with a purpose to unite science, technology, and talent to get ahead of disease together. Find out more at gsk.com. References 1 Taiwo, B et al. VH3810109 (N6LS) Efficacy and Safety in Adults Who Are Virologically Suppressed: The EMBRACE Study. Presented at the Conference on Retroviruses and Opportunistic Infections (CROI 2025), 9-12 March, San Francisco, CA SOURCE: ViiH Healthcare

Clinical ResultDrug ApprovalPhase 2Phase 3

12 Mar 2025

·www.fiercebiotech.com

GSK posts data on HIV assets vying for roles in 6-month combo

ViiV plans to make a regimen selection for treatment next year.\n GSK’s ViiV Healthcare has shared clinical data on three potential long-acting HIV treatments, providing a look at how its plans to create a six-month regimen are shaping up.ViiV, which is majority owned by GSK with Pfizer and Shionogi as shareholders, has identified demand for long-acting HIV treatments that are less burdensome for patients. With Gilead fighting hard for market share, ViiV is racing on multiple fronts to meet the demand. The company used the 2025 Conference on Retroviruses and Opportunistic Infections (CROI) in San Francisco to share data on three parts of its plan.Wednesday, ViiV published phase 2b data on its investigational broadly neutralizing antibody N6LS. The study randomized 134 adults living with HIV to receive the CD4-binding antibody intravenously or subcutaneously or continue on pre-baseline, standard-of-care antiretroviral therapy. Patients in the N6LS groups received the antibody every six months and long-acting cabotegravir every month.After six months, 96% of people on intravenous N6LS, also called VH109, maintained HIV-1 RNA levels below 50 copies/mL. The result in the standard of care group was identical. However, only 88% of people on subcutaneous N6LS maintained HIV-1 RNA levels below the threshold. Confirmed virologic failure was seen in two patients from each N6LS group. Tolerability was worse in the subcutaneous group, with 16% of patients having grade 3 or 4 redness of the skin. The results informed ViiV’s decision to take a six-month intravenous formulation of N6LS into part two of the trial. Halozyme provided the technology that enabled subcutaneous delivery.ViiV shared the N6LS data the day after publishing results from studies of two other molecules that could form part of its six-month treatment regimen. The N6LS trial used monthly cabotegravir long-acting as its integrase strand transfer inhibitor (INSTI), but ViiV could combine the antibody with its third-generation candidate VH184 down the line.At CROI, ViiV showed viral load dropped after 22 adults, who had not previously received antiretroviral therapy, started on VH184. The study provided early evidence that the INSTI can drive down viral load without causing drug resistance mutations or serious side effects. But more work is needed to show the asset can be the backbone of ViiV’s regimen, starting with a phase 1 trial of long-acting formulations.ViiV is considering N6LS and its investigational capsid inhibitor VH499 as potential partners for VH184 in its planned six-month treatment regimen. The company shared data on VH499 at CROI, linking the asset to falls in the viral loads of 23 adults who received the candidate in a phase 2 trial. One person on the low dose developed a single mutation associated with reduced susceptibility to capsid inhibitors. ViiV said the data support further development of VH499 as a potential long-acting antiretroviral for HIV treatment. A phase 1 trial is assessing long-acting formulations of the capsid inhibitor. Data from studies of VH499 and N6LS will inform the decision about which molecule to combine with VH184.Talking on a GSK earnings call last month, ViiV Chairman David Redfern said (PDF) “the aim is to look at that data this year and then make a regimen selection for treatment ... next year.” ViiV could potentially start running pivotal studies in 2027, Redfern said.

Clinical ResultPhase 2Phase 1

12 Mar 2025

·firstwordpharma.com

ViiV to pursue six-month dosing for HIV antibody after positive Phase II readout

ViiV Healthcare, GSK's HIV-focused subsidiary, is pushing forward with a new long-acting treatment for patients with HIV. After positive results from a mid-stage study, the company says it will advance development of a six-month intravenous (IV) version of its experimental antibody-based therapy, N6LS (VH109), in combination with its long-acting HIV drug cabotegravir.The Phase IIb EMBRACE trial, presented Wednesday at the Conference on Retroviruses and Opportunistic Infections (CROI), showed that N6LS, given every four months along with monthly cabotegravir injections, successfully kept the virus under control in adults already stable on treatment.Primary endpoint data showed that after six months of treatment, 96% of patients given the IV formulation of N6LS maintained HIV-1 RNA levels below 50 copies/mL — exactly matching the success rate of current standard treatments. When given as a subcutaneous (SC) injection, 88% of patients maintained HIV-1 RNA levels below 50 copies/mL. Confirmed virologic failure was observed in two participants from each N6LS group.Meanwhile, the IV option stood out as better tolerated, with no infusion site reactions — unlike the SC group, where 14% of participants reported issues."We are building on the positive patient and physician experience we have with Cabenuva (cabotegravir/rilpivirine) and pioneering the next generation of long-acting treatment options," said Kimberly Smith, head of R&D at ViiV. Cabenuva was first approved by the FDA in 2021, with the product’s label updated the following year to include dosing every two months in virologically suppressed adults."We're looking forward to continuing the development of VH109 as a component of our future ultra long-acting regimens," Smith added.The N6LS presentation was part of a broader showcase of ViiV's long-acting portfolio at CROI, where the company also presented positive findings from two Phase IIa proof-of-concept trials. These additional studies evaluated VH184, a third-generation integrase inhibitor, and VH499, a capsid inhibitor.Specifically, ViiV said VH184 led to a "marked drop" in HIV-1 viral load across all tested doses — 10 mg, 50 mg, and 300 mg taken once every three days — during a 10-day monotherapy period, with the highest average viral load decline being -2.31 log10 copies/mL in the highest dose group. Similarly, VH499 showed decreases in HIV-1 viral load ranging from -1.8 to -2.2 log10 copies/mL across its dosing arms — 25 mg, 100 mg, and 250 mg — with the highest dose producing the greatest reduction.

Clinical ResultPhase 2Drug ApprovalPhase 3

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Indication	Highest Phase	Country/Location	Organization	Date
HIV Infections	Phase 2	Argentina	ViiV Healthcare Ltd.	22 Jun 2021
HIV Infections	Phase 2	Peru	ViiV Healthcare Ltd.	22 Jun 2021
HIV Infections	Phase 2	Canada	ViiV Healthcare Ltd.	22 Jun 2021
HIV Infections	Phase 2	Mexico	ViiV Healthcare Ltd.	22 Jun 2021
HIV Infections	Phase 2	Brazil	ViiV Healthcare Ltd.	22 Jun 2021
HIV Infections	Phase 2	United States	ViiV Healthcare Ltd.	22 Jun 2021
HIV Infections	Preclinical	United States	National Institute of Allergy & Infectious Diseases	22 Jun 2021
HIV Infections	Preclinical	United States	Halozyme Therapeutics, Inc.	22 Jun 2021

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT05291520 (SPAN, CTgov)	Phase 1	HIV Infections	24	VH3810109+rHuPH20 (Part 1 Group: VH3810109 20 mg/kg + rHuPH20 [SC])	rbvgxhwttw(zbhyhnkhqw) = kpbltmbiex rczkdawodf (bhhlhoevje, ktisshenpm - hjzojshvey) View more	-	19 Sep 2024
				VH3810109+rHuPH20 (Part 3 Group: VH3810109 3000 mg + rHuPH20 [SC])	rbvgxhwttw(zbhyhnkhqw) = xkimaotzxz rczkdawodf (bhhlhoevje, bpgveuxmgb - wolkisjsae) View more
NCT04871113 (CTgov)	Phase 2	HIV Infections	62	GSK3810109A (Part 1:GSK3810109A 40milligram(mg)/Kilogram Intravenously (IV))	etjmlmmlnx(gfrscqdtoq) = yogwzvforc pvronnxswv (hxuyupjveu, trwazgeuwq - vnmphcpgaz) View more	-	18 Nov 2023
				GSK3810109A (Part 1: GSK3810109A 280 mg IV)	etjmlmmlnx(gfrscqdtoq) = kjyxuuhunj pvronnxswv (hxuyupjveu, omsohwdanh - jmbsrtpzjh) View more
NCT03538626 (VRC 609, CTgov)	Phase 1	HIV Infections	33	VRC-HIVMAB091-00-AB (Group 1: N6LS (5 mg/kg IV) Single Dose)	ckwlkuinmy(yflondepkm) = fdwhmflrkr qsasrjokpt (ioktigdwli, ltrepmasmb - ueechrixpd) View more	-	21 Sep 2023
				VRC-HIVMAB091-00-AB (Group 2: N6LS (5 mg/kg SC) Single Dose)	ckwlkuinmy(yflondepkm) = dcfkvcjsyw qsasrjokpt (ioktigdwli, gfwvlclyxl - nkvkaqfwhw) View more

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