ViiV Healthcare submits New Drug Application to the FDA for fostemsavir, an investigational, first-in-class attachment inhibitor for the treatment of HIV in adults with few treatment options available
Antiretroviral medicines that can effectively suppress HIV have been instrumental in decreasing disease progression, HIV transmission, and AIDS-related deaths, but because of HIV’s ability to constantly change, some individuals can develop viral resistance to antiretroviral medicines, causing their treatment regimens to fail. Challenges with tolerability, safety, and drug-to-drug interactions may further decrease the number of acceptable antiretroviral therapies available to design effective treatment regimens. There remains an unmet need for these individuals who are considered heavily treatment-experienced and who are unable to successfully suppress their HIV.
This submission is supported by the data from the pivotal phase III BRIGHTE study in heavily treatment-experienced people living with multidrug-resistant HIV. The 96-week results from the BRIGHTE study were most recently presented in July at the 10th
Fostemsavir has been granted FDA Fast Track and Breakthrough Therapy Designations. These programmes are intended to facilitate and expedite the development and review of new drugs to address unmet medical need in the treatment of a serious or life-threatening condition. Eligibility for Breakthrough Therapy Designation requires that preliminary clinical evidence indicate that the drug may demonstrate substantial improvement on clinically significant endpoint(s) over available therapies.
The efficacy of fostemsavir in heavily treatment-experienced adults with HIV-1 infection is based on 96-week data from the phase III, partially-randomised, international, double-blind, placebo-controlled BRIGHTE study (NCT02362503).
The BRIGHTE trial was conducted in 371 heavily treatment-experienced 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 antiretroviral medications remaining at baseline due to resistance, intolerability, contraindication, or other safety concerns. 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 antiretroviral 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.
- Within the nonrandomised cohort (n = 99), participants had no fully active and approved antiretroviral 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%, 54%, and 60% of subjects at Weeks 24, 48, 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, 139 cells/mm3 at Week 48, and 205 cells/mm3 at Week 96). The most common adverse reactions (incidence ≥5%, all grades) were nausea and diarrhoea. The proportion of participants who discontinued treatment with fostemsavir due to an adverse event was 7% at Week 96 (randomised: 5% and nonrandomised: 12%).
Fostemsavir, an investigational prodrug of temsavir, is a first-in-class HIV-1 attachment inhibitor that works by binding directly to the glycoprotein 120 (gp120) subunit on the surface of the virus. By binding to this location on the virus, fostemsavir blocks HIV from attaching to host immune system CD4+ T-cells and other immune cells, thereby preventing HIV from infecting those cells and multiplying. Because of this unique mechanism of action, there is no demonstrated resistance to other classes of antiretrovirals, which may help patients who have become resistant to most other medicines. Fostemsavir is not yet approved by regulatory authorities anywhere in the world and is being developed by
About ViiV Healthcare
ViiV Healthcare is a global specialist HIV company established in
For more information on the company, its management, portfolio, pipeline and commitment, please visit www.viivhealthcare.com.
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