ViiV Healthcare, the global specialist HIV company majority owned by GlaxoSmithKline plc (“GSK”), with Pfizer Inc. and Shionogi Limited as shareholders, today announced that the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) issued a positive opinion recommending approval of Rukobia (fostemsavir) 600 mg extended-release tablets, a novel attachment inhibitor for the treatment of HIV-1 infection. Fostemsavir, 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.1
Deborah Waterhouse, CEO of ViiV Healthcare, said: “While incredible strides have been made in treating HIV over the past few decades, a select population of adults with multidrug resistant HIV-1 infections are not able to maintain viral suppression with currently available medication. Without effective new options, this group of people are at risk of progressing to AIDS, so a positive opinion from the CHMP for fostemsavir is extremely welcome news and is an important step towards ensuring no one is left behind at any stage of living with HIV. We are committed to pursuing innovative research to meet the diverse needs of the HIV community, and this positive CHMP opinion comes from the culmination of complex research, development and manufacturing. We won’t stop until we have more ways to treat, and hopefully one day cure, HIV.”
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 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 meaningful improvements to CD4+ T-cell count at Week 96.2,3
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
Final Marketing Authorisation from the European Commission is anticipated in the coming months. Fostemsavir, under the brand name Rukobia, was recently approved by the US Food and Drug Administration on 2 July 2020, and further regulatory applications have been submitted worldwide.
ViiV Healthcare’s mission is to ensure that no one living with HIV is left behind. 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 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 who have become resistant to most other medicines.
The BRIGHTE trial is an international, phase III, partially-randomised, double-blind, placebo-controlled study conducted in 371 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 nonrandomised 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 optimized background therapy (OBT).
- Within the nonrandomised cohort (n = 99), participants had no fully active and approved ARV agent(s) available at screening. Nonrandomised 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 nonrandomised 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 nonrandomised cohort, HIV-1 RNA <40 copies/mL was achieved in 37% of subjects at Weeks 24 and 96. At these timepoints, 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 adverse reactions reported in nonrandomised subjects were fatigue (7%), nausea (6%), and diarrhoea (6%).
Important Safety Information (ISI) in EU
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.
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.
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:
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.
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 www.gsk.com/about-us.
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 Q3 Results and any impacts of the COVID-19 pandemic.
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1 EMA SmPC – European Medicines Agency. Rukobia Summary of Opinion. Available at https://www.ema.europa.eu/en/medicines/human/summaries-opinion/rukobia. Accessed December 2020.
2 Kozal, M., et al. 2020. Fostemsavir in Adults with Multidrug-Resistant HIV-1 Infection. New England Journal of Medicine, 382(13), pp.1232-1243.
3 Lataillade, M., et al. 2020. Safety and efficacy of the HIV-1 attachment inhibitor prodrug fostemsavir in heavily treatment-experienced individuals: week 96 results of the phase 3 BRIGHTE study. The Lancet, Vol 7 Nov 2020 pp.740-751.
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