ViiV Healthcare announces positive CHMP opinion for Rukobia (fostemsavir), a first-in-class attachment inhibitor for the treatment of adults with multidrug-resistant HIV with few treatment options available

• Findings from pivotal phase III BRIGHTE study demonstrated that the majority (60%) of heavily treatment-experienced adults randomised to receive fostemsavir with an optimised background therapy achieved and maintained viral suppression at 96 weeks
• Fostemsavir addresses a critical unmet need in HIV care for those with little to no treatment options left

London, 11  December, 2020 – 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. [i]

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.[ii]^,[iii]

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,[iv] 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. 

About BRIGHTE

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%). 

[i] 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.

[ii] Kozal, M., et al. 2020. Fostemsavir in Adults with Multidrug-Resistant HIV-1 Infection. New England Journal of Medicine, 382(13), pp.1232-1243.

[iii] 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.

 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 www.gsk.com/about-us.