ViiV Healthcare receives Marketing Authorisation for Rukobia (fostemsavir), a first-in-class attachment inhibitor in combination with other antiretrovirals for the treatment of adults with multidrug-resistant HIV

London, 08 February 2021 – ViiV Healthcare, the global specialist HIV company majority owned by GlaxoSmithKline plc (“GSK”), with Pfizer Inc. and Shionogi Limited as shareholders, announced the European Marketing Authorisation of Rukobia (fostemsavir) 600mg extended-release tablets, for use in combination with other antiretroviral (ARV) therapies for the treatment of adults with multidrug-resistant HIV-1 infection, for whom it is otherwise not possible to construct a suppressive anti-viral regimen.¹ Fostemsavir is a first-in-class HIV attachment inhibitor; it works by targeting the first step of the HIV lifecycle and shows no cross-resistance to other currently licensed antiretroviral classes, offering a new option to this group of people who are multidrug-resistant and at risk of disease progression and death.

Prof Carlo Federico Perno, Director, Microbiology and Diagnostic Immunology, Pediatric Hospital Bambino Gesu', Rome said: “We’ve seen significantly improved HIV treatments becoming available over the past few decades, making HIV a manageable life-long condition. However, for some people who are living with multidrug-resistant HIV, there is an urgent need for new treatment options. In clinical trials, fostemsavir, in combination with other antiretroviral therapies, demonstrated sustained rates of virologic suppression and clinically meaningful CD4+ T-cell recovery offering us a long-awaited new option for this specific HIV community.”

The Marketing Authorisation Application (MAA) for fostemsavir is supported by data from the pivotal phase III BRIGHTE study, which evaluated the safety and efficacy of fostemsavir in combination with an optimised background therapy (OBT) in heavily treatment experienced (HTE) adults living with multidrug-resistant HIV, many of whom had advanced HIV disease at study entry. In the randomised cohort, 60% (n=163/272) of individuals who received fostemsavir in addition to an investigator-selected OBT achieved undetectable HIV viral load and clinically significant improvements to CD4+ T-cell count through Week 96.²

Deborah Waterhouse, CEO of ViiV Healthcare, said: “There have been great strides in the HIV treatment landscape over the last few decades, however, there still remains a small subset of people living with multi-drug resistant HIV who are at risk of having their disease progress. The Marketing Authorisation for fostemsavir marks a significant milestone, as it addresses a critical unmet need in HIV care for those with little or no treatment options left. At ViiV Healthcare, through our pioneering research and development, we aim to meet the diverse needs of the HIV community. We won’t stop until our research offers more ways to treat, and hopefully one day, cure HIV.”

The most commonly seen treatment emergent adverse reactions were diarrhoea (24%), headache (17%), nausea (15%), rash (12%), abdominal pain (12%), and vomiting (11%). The most common adverse events leading to discontinuation were related to infections (3%). The most serious adverse reaction was immune reconstitution inflammatory syndrome.¹

Fostemsavir, under the brand name Rukobia, was licensed by the US Food and Drug Administration on 2 July 2020, and further regulatory applications have been submitted worldwide.

As the only pharmaceutical company solely focused on HIV and AIDS, ViiV Healthcare is working to deliver a broad range of treatments that meet the needs of a wide variety of people living with HIV (PLHIV). The company continues to invest in R&D programmes that push the boundaries to provide a portfolio of innovative treatment options that will help make a difference to the lives of PLHIV.

About Rukobia (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 ARV therapy to target this step of the viral cycle, there is no demonstrated resistance to other classes of ARVs, which may help patients whose HIV infection has become resistant to most other medicines.

About BRIGHTE

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 600 mg 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 600 mg 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 600 mg 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).

In the randomised cohort, HIV-1 RNA <40 copies/mL was achieved in 53% and 60% of subjects at Weeks 24 and 96, respectively (ITT-E, Snapshot algorithm). Mean changes in CD4+ cell count from baseline continued to increase over time (i.e., 90 cells/mm³ at Week 24 and 205 cells/mm³ at Week 96). In the non-randomised cohort, HIV-1 RNA <40 copies/mL was achieved in 37% of subjects at Weeks 24 and 96. At these time points, the proportion of subjects with HIV-1 RNA <200 copies/mL was 42% and 39%, respectively (ITT-E, Snapshot algorithm). Mean changes in CD4+ cell count from baseline increased over time: 41 cells/mm³ at Week 24 and 119 cells/mm³ at Week 96. The most common drug-related adverse events reported in non-randomised subjects were fatigue (5%), nausea (6%), and diarrhoea (6%). The most common drug-related adverse events reported in the randomised subjects were nausea (10%), diarrhoea (4%), headache (4%) and immune reconstitution inflammatory syndrome (2%).

Important Safety Information (ISI) in EU

THERAPEUTIC INDICATIONS

Rukobia, in combination with other antiretrovirals, is indicated for the treatment of adults with multidrug resistant HIV-1 infection for whom it is otherwise not possible to construct a suppressive anti-viral regimen.

POSOLOGY AND METHOD OF ADMINISTRATION

Recommended dose is 600mg Fostemsavir twice daily.

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.

SPECIAL WARNINGS AND PRECAUTIONS FOR USE

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 QT interval prolongation, when co-administered with a medicine with a known risk of Torsade de Pointes, or in patients with relevant pre-existing cardiac disease. Elderly patients may be more susceptible to drug-induced QT interval prolongation.

Patients with Hepatitis B and C co-infection:

Elevations in hepatic transaminases may occur 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.

Restricted range of antiviral activity:

It is recommended that Rukobia is not used to treat infections due to HIV-1 Group M subtype AE strains.

Risk of Adverse Reactions or Loss of Virologic Response Due to Drug Interactions:

• ADVERSE REACTIONS
  The most commonly seen treatment adverse reactions were diarrhoea, headache, and nausea.

• INTERACTIONS WITH OTHER MEDICINAL PRODUCTS.
  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.
  Doses of oral contraceptives should not contain more than 30 mcg of ethinyl estradiol per day.

• USE IN SPECIFIC POPULATIONS:
  Safety and efficacy of Rukobia has not been established in children and adolescents less than 18 years old. There is limited data on the use of Rukobia during pregnancy and as a precaution Rukobia should be avoided in pregnancy.

About ViiV Healthcare

ViiV Healthcare is a global specialist HIV company established in November 2009 by GlaxoSmithKline (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 joined in October 2012. The company’s aim is to take a deeper and broader interest in HIV/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 science-led global healthcare company with a special purpose: to help people do more, feel better, live longer. For further information please visit https://www.gsk.com/en-gb/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 under Item 3.D "Risk Factors" in the company's Annual Report on Form 20-F for 2019 and as set out in GSK’s “Principal risks and uncertainties” section of the Q4 Results and any impacts of the COVID-19 pandemic.

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