dm+d

Unassigned

New Medicines

DescovyHIV infection - pre-exposure prophylaxis

Information

Descovy
Licence extension / variation
Gilead Sciences
Gilead Sciences

Development and Regulatory status

Launched
Phase III Clinical Trials
Launched
April 2022
Apr 22MHRA approves a licence extension for Descovy 200mg/25mg tablets, for pre-exposure prophylaxis to reduce the risk of sexually acquired HIV-1 infection in at-risk men who have sex with men, including adolescents (with body weight at least 35 kg) [17].
Jan 22This is not approved in UK yet for this indication. [14,15]
Jan 20Gilead currently reviewing feedback from EC re MAA process in EU for this indication. [10]
Oct 19Approved in the US to reduce the risk of sexually acquired HIV-1 infection in adults and adolescents weighing at least 35 kg who are HIV-negative and at-risk for sexually acquired HIV, excluding individuals at-risk from receptive vaginal sex [9].
Aug 19In the US, the Antimicrobial Drugs Advisory Committee (AMDAC) of the FDA has recommended approval of Descovy for the proposed indication of pre-exposure prophylaxis (PrEP) in men and transgender women by a vote of 16 to 2. The AMDAC also evaluated pharmacokinetic data in support of the potential use of Descovy for PrEP in cis-gender women, a population that was not part of the DISCOVER study. The committee voted 10 to 8 that there were not adequate data regarding the efficacy of Descovy for PrEP in this population [8].
Apr 19sNDA submitted to FDA with priority review. Application is based on data from PIII DISCOVER study which compared Descovy vs Truvada (emtricitabine 200 mg with tenofovir disoproxil fumarate 300 mg tablets) in men and transgender women who have sex with men at high-risk for sexually acquired HIV infection [7].
Mar 19Positive PIII non-inferiority data is available and will support filing for PrEP indication [5,6].
Mar 18In PIII trial.[3]

Category

Fixed dose combination of emtricitabine and tenofovir alafenamide (F/TAF), as a single tablet formulation, containing a nucleoside transcriptase inhibitor and nucleotide reverse transcriptase inhibitor.
The eligible population is difficult to estimate and will fluctuate. The number of HIV-negative men and transgender women who have sex with men and attend sexual health clinics was 120,606 in 2016. Based on this, there could be ~120,000 people in England who may be eligble to use HIV pre-exposure prophylaxis. [13]
HIV infection - pre-exposure prophylaxis
Oral

Trial or other data

Mar 22NICE agreed that a Technology Appraisal (TA) would not be appropriate for the subject technology due to the commissioning arrangements being covered in the existing NHS England policy https://www.england.nhs.uk/wp-content/uploads/2017/03/f03-taf-policy.pdf [16].
Jul 20The PIII DISCOVERY trial n=5,857) is published; it found emtricitabine and tenofovir alafenamide was non-inferior to emtricitabine and tenofovir disoproxil fumarate for HIV prevention (incidence rate ratio 0.47; 95% CI 0.19-1.15 [upper limit below prespecified non-inferiority margin of 1.62]) [11].
Aug 19Gilead propose positioning Descovy as a safer alternative to Truvada, which is set to lose U.S. patent protection Sept 2019, suggesting it shows superior safety for bone and renal as well as rapid onset and longer duration of preventative therapy. However the FDA Panel has flagged the lack of data to demonstrate superiority of Descovy to Truvada and has stressed that the non-inferiority nature of the safety and efficacy profile between Descovy and Truvada needs to be adequately communicated in the commercial setting [8].
Mar 19Results from the PIII DISCOVER trial have been released by Gilead. Their new combination (Descovy) demonstrated non-inferiority to their established combination (Truvada) in terms of the primary efficacy endpoint of HIV infection. The company is claiming a numerical benefit of Descovy over Truvada for this outcome, but this was not statistically significant. Additionally, in pre-specified secondary endpoints, statistically significant advantages relating to bone (1% difference in BMD) and renal (2-4mL/min difference in renal function) laboratory parameters were noted, though these are likely to be considered small benefits [5,6].
Mar 18PIII DISCOVER Study (NCT02842086) still active with an estimated primary completion date of February 2019.[3]
Sep 16PIII trial to evaluate safety and efficacy of oral once-daily emtricitabine/tenofovir alafenamide and of emtricitabine/tenofovir disoproxil fumarate for pre-exposure prophylaxis of HIV-1 infection in men (MSM) and transgender women (TGW) who have sex with men starts (NCT02842086). The randomised, double-blind trial is recruiting 5,000 MSM and TGW, who are at risk of the infection, in the US, Austria, Canada, Denmark, France, Germany, Ireland, Netherlands, Spain and the UK. Primary outcome is incidence of seroconversions per 100 person-years as defined by the HIV-1 RNA by Polymerase Chain Reaction (PCR); collection of these data should complete Feb 19 [2].

DescovyHIV infection in children aged 6 to 12 years

Information

Descovy
Licence extension / variation
Gilead Sciences
Gilead Sciences

Development and Regulatory status

None
None
Launched
Jan 22Not yet approved for use in this age group. [6,7]
Sep 17Approved for use in US in combination with other antiretroviral agents other than protease inhibitors that require a CYP3A inhibitor for the treatment of HIV-1 infection in pediatric patients weighing at least 25 kg and less than 35 kg. [4,5]

Category

Fixed dose combination of emtricitabine and tenofovir alafenamide (F/TAF), as a single tablet formulation, containing a nucleoside transcriptase inhibitor and nucleotide reverse transcriptase inhibitor.
In 2017, 42 children were newly diagnosed with HIV – down from 131 in 2005. All these children were born in other countries [8].
HIV infection in children aged 6 to 12 years
Oral

Trial or other data

Jan 22PII/III study (NCT01854775) is has finished recruiting and is active with a primary completion date of May 20 and a study completion date of Dec 22 now. [8]
Jan 21PII/III study (NCT01854775) is has finished recruiting and is active with a primary completion date of May 20 and a study completion date of Dec 21. [4]
Dec 18PII/III study (NCT01854775) is recruiting [2].
May 13PII/III study (NCT01854775) starts. There will be 3 cohorts in this study, each consisting of Part A and Part B. The primary objectives of Cohort 2 are to evaluate the PK of EVG and TAF in virologically suppressed HIV-1 infected children 6 to < 12 years of age weighing ≥ 25 kg administered E/C/F/TAF STR (Part A) and to evaluate the safety and tolerability of E/C/F/TAF STR through Week 24 in virologically suppressed HIV-1 infected children 6 to < 12 years of age weighing ≥ 25 kg (Part B). Collection of primary outcome data is due to complete Jul 20 [2].