Week 240 data from the BRIGHTE-study of first-in-class fostemsavir continue to show improvement in immunologic response and favourable virologic outcomes

ViiV Healthcare, the global specialist HIV company majority owned by GSK, with Pfizer and Shionogi as shareholders, today announced week 240 results from the phase III BRIGHTE study of fostemsavir in heavily treatment-experienced (HTE) adults with multidrug-resistant HIV-1 infection who have very few treatment options left available to them due to resistance, intolerance, or other safety concerns.

The BRIGHTE study is an international, two-cohort (randomised and non-randomised), phase III clinical trial evaluating the safety and efficacy of fostemsavir, a first-in-class attachment inhibitor, used in combination with optimised background treatment (OBT) in 371 patients from 113 sites across 22 countries. Study findings showed that people living with multidrug-resistant HIV-1 treated for approximately five years with fostemsavir-based regimens experienced durable virologic responses and continued clinically meaningful improvements in CD4+ cell count and CD4+/CD8+ ratio.¹ These findings were shared today during the 24^th International AIDS Conference (AIDS 2022) in Montreal, Canada.

Kimberly Smith, M.D., Head of Research & Development at ViiV Healthcare, said: “These results are so significant because fostemsavir is the only treatment available for this specific population, with such long-term, thorough data. With such a clinically meaningful improvement in CD4+ count in the study population, these extensive and robust study findings demonstrate the durability of fostemsavir and its suitability as a treatment for these people living with HIV. Given these findings fostemsavir remains a good representation of our commitment to developing innovative medicines for all people living with HIV, regardless of where they are in their treatment journey.”

In the randomised cohort, rates of virologic response generally remained consistent over time through week 240, with 45% (120/272) of patients receiving fostemsavir plus OBT in the randomised cohort achieving virologic suppression (HIV-1 RNA <40 copies per millilitre [c/mL]).¹ Reduced virologic response rates by Snapshot analysis beyond week 192 were partially confounded by missing data because of COVID-19 pandemic as well as changes in OBT.¹ CD4+ cell counts increased steadily from baseline (n = 272) over time and increased by 296 cells/mm³ by week 240. In the randomised cohort, 78% (73/94) of participants had a change in CD4+ cell count from <200 cells/mm³ to ≥200 cells/mm³, and 67% (22/33) had a change from <20 cells/mm³ to ≥200 cells/mm³.¹ CD4+/CD8+ ratio also increased steadily from baseline, reaching a mean of 0.6 in the randomised cohort by week 240.¹

At week 240, the safety profile was consistent with earlier findings across both cohorts, and no new trends in the safety data were identified.¹ In the randomised cohort, 95% (259/272) of patients experienced at least one adverse event (AE), with the most common drug-related AEs across both groups being nausea (35/371, 9%) and diarrhoea (18/371, 5%). At least one serious adverse event (SAE) was experienced by 45% (122/272) of patients in the randomised cohort, the most common of which were due to infections and not related to the study medication (fostemsavir + OBT). In total, 4% (10/272) of SAEs in the randomised cohort were related to the study medication, with 4 participants discontinuing because of an AE between week 96 and week 240. Of 35 deaths, 12 were AIDS-related (5 new since week 96), 12 were acute infections (1 new since week 96), 6 were non-AIDS-related malignancies, and the remaining 5 were related to other conditions. During the study, 25/371 participants were diagnosed with 28 COVID-19 and COVID-19 related events. All cases resolved without reported sequelae, and there were no COVID-19 related deaths or reports of post-COVID-19 syndrome.

About fostemsavir

Fostemsavir is a first-in-class HIV-1 attachment inhibitor. After oral administration, fostemsavir is converted to temsavir, which is then absorbed and exerts antiviral activity by attaching directly to the glycoprotein 120 (gp120) subunit on the surface of the virus, thereby blocking HIV from attaching to host immune system CD4+ T-cells and preventing the virus from infecting those cells and multiplying. As fostemsavir is the first antiretroviral (ARV) therapy to target this step of the viral cycle, there is no demonstrated resistance to other classes of ARVs, which may help people living with HVI whose HIV has become resistant to most other medicines.

About BRIGHTE (NCT02362503)

The BRIGHTE trial is an international, phase III, partially-randomised, double-blind, placebo-controlled study conducted in 371 heavily treatment-experienced (HTE) adults living with HIV-1 infection with multidrug resistance. All trial participants were required to have a viral load ≥400 copies/mL and ≤2 classes of ARV medications remaining at baseline due to resistance, intolerability, contraindication, or other safety considerations. Trial participants were enrolled in either a randomised or non-randomised cohort defined as follows:

• Within the randomised cohort (n = 272), participants had 1, but no more than 2, fully active and available ARV agent(s) at screening, which could be combined as part of an efficacious background regimen. Randomised participants received either blinded fostemsavir 600mg twice daily (n = 203) or placebo (n = 69) in addition to their current failing regimen for 8 days of functional monotherapy. Beyond Day 8, randomised participants received open-label fostemsavir 600mg twice daily plus an investigator-selected optimised background therapy (OBT). The randomised cohort provides primary evidence of efficacy of fostemsavir.
• Within the non-randomised cohort (n = 99), participants had no fully active and licensed ARV agent(s) available at screening. Non-randomised participants were treated with open label fostemsavir 600mg twice daily plus OBT from Day 1 onward. The use of an investigational drug(s) as a component of the optimised background therapy was permitted in the non-randomised cohort.

The primary endpoint analysis, based on the adjusted mean decline in HIV-1 RNA from Day 1 at Day 8 in the randomised cohort, demonstrated superiority of fostemsavir to placebo (0.79 vs 0.17 log₁₀ copies/mL decline, respectively; P<0.0001, Intent-to-Treat-Exposed [ITT-E] population).

About the patient population

ARV medicines have significantly decreased mortality over the past 30 years; however, treatment failure and antiviral resistance remain a concern for heavily treatment-experienced patients and their healthcare providers. Failure of HIV medicines to control the virus can result in selected mutations resistant to one or more ARV medicines. Patient co-morbidities, tolerability and safety issues may further decrease the number of ARV therapies available to design effective treatment regimens for these heavily treatment-experienced patients. As a result, treatment options that address the complex needs of heavily treatment-experienced people living with HIV remain a significant unmet need.

Important Safety Information (ISI)

The following ISI is based on the Highlights section of the Prescribing Information for RUKOBIA. Please consult the full Prescribing Information for all the labelled safety information for RUKOBIA.

INDICATIONS AND USAGE

• RUKOBIA, a human immunodeficiency virus type 1 (HIV-1) gp120-directed attachment inhibitor, in combination with other antiretroviral(s), is indicated for the treatment of HIV-1 infection in heavily treatment-experienced adults with multidrug-resistant HIV-1 infection failing their current antiretroviral regimen due to resistance, intolerance, or safety considerations.

DOSAGE AND ADMINISTRATION

• One tablet taken twice daily with or without food.

DOSAGE FORMS AND STRENGTHS

• Extended release tablets: 600 mg

CONTRAINDICATIONS

• Hypersensitivity to fostemsavir or any of the components of the formulation.
• Coadministration with strong cytochrome P450 (CYP)3A inducers as significant decreases in temsavir plasma concentrations may occur, which may result in loss of virologic response.

WARNINGS AND PRECAUTIONS

• Immune reconstitution syndrome has been reported in patients treated with combination antiretroviral therapies.
• QTc prolongation: Use RUKOBIA with caution in patients with a history of QTc prolongation or with relevant pre-existing cardiac disease or who are taking drugs with a known risk of Torsade de Pointes.
• Elevations in hepatic transaminases in patients with hepatitis B or C virus co-infection: Elevations in hepatic transaminases were observed in a greater proportion of subjects with HBV and/or HCV co-infection compared with those with HIV mono-infection.
• Risk of Adverse Reactions or Loss of Virologic Response Due to Drug Interactions: The concomitant use of RUKOBIA and certain other drugs may result in known or potentially significant drug interactions, some of which may lead to 1) Loss of therapeutic effect of RUKOBIA and possible development of resistance due to reduced exposure of temsavir 2) Possible prolongation of QTc interval from increased exposure to temsavir.

ADVERSE REACTIONS

• The most common adverse reactions (all grades) observed in ≥5% of randomized and non-randomized participants were nausea, fatigue and diarrhea.

DRUG INTERACTIONS

• See full prescribing information for complete list of significant drug interactions.
• Doses of oral contraceptives should not contain more than 30 mcg of ethinyl estradiol per day.

USE IN SPECIFIC POPULATIONS

• Lactation: Breastfeeding is not recommended due to the potential for HIV-1 transmission.

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 are at risk of becoming infected with HIV. Shionogi B.V. joined as shareholders 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 www.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/company.

Cautionary statement regarding forward-looking statements

GSK cautions investors that any forward-looking statements or projections made by GSK, including those made in this announcement, are subject to risks and uncertainties that may cause actual results to differ materially from those projected. Such factors include, but are not limited to, those described in the Company's Annual Report on Form 20-F for 2021, GSK’s Q1 Results for 2022 and any impacts of the COVID-19 pandemic.

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References:

¹ Aberg J et al. Safety and Efficacy of Fostemsavir Plus Optimized Background Therapy in Heavily Treatment-Experienced Adults With HIV-1: Week 240 Results of the Phase 3 BRIGHTE Study. Presented at AIDS 2022.

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