dm+d

Unassigned

New Medicines

Vocabria (EU), Cabenuva and Vocabria (US) HIV infection in patients on a stable anti-retroviral regimen with no evidence of relevant resistance - in combination with rilpivirine

Information

Vocabria (EU), Cabenuva and Vocabria (US)
New molecular entity
ViiV Healthcare
Janssen

Development and Regulatory status

Launched
Approved (Licensed)
Approved (Licensed)
October 2021
Oct 21Available in the UK. Price 1 x 3ml vial = £1197.02 [23,24].
Jan 21The FDA also approved Vocabria (cabotegravir, tablet formulation), which should be taken in combination with oral rilpivirine (Edurant) for one month prior to starting treatment with Cabenuva to ensure the medications are well-tolerated before switching to the extended-release injectable formulation [20].
Jan 21Cabenuva consists of two injectable medicines – cabotegravir and rilpivirine – and is dosed once monthly [19].
Jan 21Vocabria in the UK is licensed for use in combination with rilpivirine injection, for the treatment of Human Immunodeficiency Virus type 1 (HIV-1) infection in adults who are virologically suppressed (HIV-1 RNA <50 copies/mL) on a stable antiretroviral regimen without present or past evidence of viral resistance to, and no prior virological failure with agents of the NNRTI and INI class [22].
Jan 21Approved in UK [22].
Jan 21Approved in US [19]
Dec 20Approved in EU [18].
Oct 20Recommended for EU approval by CHMP - the full indication is "in combination with rilpivirine injection, for the treatment of Human Immunodeficiency Virus type 1 (HIV-1) infection in adults who are virologically suppressed (HIV-1 RNA <50 copies/mL) on a stable antiretroviral regimen without present or past evidence of viral resistance to, and no prior virological failure with agents of the NNRTI and INI class (see sections 4.2, 4.4 and 5.1). Vocabria should be prescribed by physicians experienced in the management of HIV infection.” [16]
Dec 19US FDA has rejected cabotegravir in combination with rilpivirine for the treatment of HIV in virologically suppressed adults. The reasons outlined in the FDA complete response letter (CRL) relate to chemistry manufacturing and controls, but there have been no reported safety issues related to this. The manufacturer will work with the FDA to determine the next steps for this regimen’s marketing application [13].
Jul 19Filed in EU [12]
Apr 19Filed in US [11].
Mar 18In PIII trials.
Feb 16PIII studies to start later in 2016 [3]
Nov 15Johnson & Johnson plus Viiv are planning a PIII study with the goal of launch by 2020 [3].

Category

Cabotegravir is an HIV integrase strand transfer inhibitor (INSTI) injected twice monthly. Rilpivirine is an NNRTI. An oral preparation is also being licensed. Plus in the US an IM preparation combined with rilpivirine (Cabenuva).
In 2016, ~89,400 people in England were living with HIV and nearly all are infected with the HIV-1 strain. [9]
HIV infection in patients on a stable anti-retroviral regimen with no evidence of relevant resistance - in combination with rilpivirine
Intramuscular

Further information

Yes

Trial or other data

Oct 21Week 96 analysis of ATLAS-2M study show 8-week dosing of long-acting cabotegravir and rilpivirine was non-inferior to every 4-week dosing (2% v 1%, respectively, with HIV-1 RNA ≥50 copies/mL; adjusted treatment difference of 1.0 [95% CI −0.6 to 2.5]) [25].
Apr 21Extension of PIII FLAIR RCT (n=566) found long-acting cabotegravir & rilpivirine continued to be non-inferior vs continuing a standard care regimen in adults with HIV-1 for the maintenance of viral suppression at 96 weeks (3% had >50 HIV RNA copies per mL in both groups) [19].
Dec 20Dec 20: The ATLAS-2M RCT (n=1045) found that cabotegravir plus rilpivirine long-acting every 8 weeks was non-inferior to dosing every 4 weeks (HIV-1 RNA ≥50 copies per mL; 2% vs 1%) with an adjusted treatment difference of 0·8 (95% CI −0·6–2·2) supporting use of this 2-monthly regimen [17].
Mar 20PIII ATLAS RCT (NCT02951052; n=716) is published; it found monthly injections of long-acting cabotegravir and rilpivirine noninferior to standard oral therapy for maintaining HIV-1 suppression at week 48 (HIV-1 RNA ≥50 copies/ml in 5 people (1.6%) vs. 3 (1.0%) on oral; difference, 0.6%; 95% CI, −1.2-2.5) [15].
Mar 20PIII FLAIR RCT (NCT02938520; n=566) is published; it found that therapy with long-acting injections plus rilpivirine was noninferior to oral therapy with dolutegravir–abacavir–lamivudine with regard to maintaining HIV-1 suppression at week 48 [HIV-1 RNA ≥50 copies/ml in 6 (2.1%) vs. 7 (2.5%) on oral therapy] [14].
Mar 19ViiV announces results from two pivotal PIII trials (FLAIR and ATLAS) demonstrating a long-acting, once-monthly injectable regimen of cabotegravir and rilpivirine is non-inferior to an oral, daily, three-drug combination standard of care. ATLAS met its primary endpoint by demonstrating non-inferior virologic suppression at 48 weeks. Confirmed virologic failure was infrequent, with three patients in the treatment arm and four patients in the active control arm. FLAIR met is primary endpoint by demonstrating non-inferiority of this two drug combination to a four drug combination at 48 weeks. Three confirmed virologic failures were noted in both arms [12].
Aug 18Viiv announce positive topline results from PIII ATLAS trial. Patients with viral suppression switched to long acting cabotegravir and rilpivirine (once monthly injections) had a similar efficacy to daily oral triple therapy for HIV at week 48, meeting the primary endpoint for non-inferiority [8].
Nov 17Viiv announce start of another PIII trial, NCT03299049 (ATLAS-2M), to demonstrate non-inferior efficacy and safety of cabotegravir in combination with rilpivirine administered every 8 weeks (Q8W) vs every 4 weeks (Q4W). This will be a randomised, multicentre, parallel group, open label trial. Estimated primary completion date is Feb 2022, with initial results anticipated in 2019. The study plans to recruit 1,020 participants, approximately half of whom will come from the ATLAS trial. Participants will be divided into two groups: Group 1 will include participants receiving current anti-retroviral standard of care (SOC) therapy whereas Group 2 will include participants currently receiving cabotegravir + rilpivirine Q4W in the ATLAS study. Participants in both groups will be randomised to receive cabotegravir + rilpivirine Q4W or Q8W. Following an oral lead in for SOC participants, the study will be carried out in three phases including a screening phase, maintenance phase and extension phase. Participants choosing not to enter the extension phase can complete their study participation at the Week 100 visit and enter the 52-week Long-Term Follow-Up Phase [6,7].
Jul 17Results of PIIb trial NCT02120352 (LATTE-2) published in The Lancet. RCT (n=286) reports that at 32 weeks follow-up, the two-drug combination of all-injectable, long-acting cabotegravir plus rilpivirine every 4 weeks or every 8 weeks was as effective as daily three-drug oral therapy at maintaining HIV-1 viral suppression [5].
Nov 16ViiV Healthcare announce two PIII clinical trials. FLAIR (First Long-Acting Injectable Regimen) (NCT02938520) and ATLAS (Antiretroviral Therapy as Long-Acting Suppression) (NCT02951052), will examine the safety and efficacy of monthly dosing with the two-drug, injectable regimen in both treatment-naïve and treatment-experienced patients [4].
Nov 15ViiV and Janssen announce results from a PIIb trial of 309 HIV patients given standard three-drug therapy until they achieved viral suppression. From there, investigators split the group in three, keeping some patients on daily pills and giving others either monthly or every-8-weeks injections of rilpivirine and cabotegravir. After 96 weeks, rates of viral suppression were consistent across all three arms of the study, with 95% for the 8-week group, 94% for the four-week patients and 91% for those on three pills a day [1].
Apr 14ViiV Healthcare initiate a PIIb trial, in collaboration with Janssen Pharmaceuticals and GlaxoSmithKline, to assess the antiviral activity (maintenance of virologic suppression), tolerability and safety of two intramuscular regimens of rilpirivine plus cabotegravir, compared with cabotegravir plus abacavir/lamivudine, in antiretroviral-naive patients with HIV-1 infections (200056; NCT02120352; EudraCT2013-000783-29). Patients will receive an oral induction regimen of cabotegravir and abacavir/lamivudine. The trial completed enrolment of planned 265 patients in the US, Canada, France, Germany and Spain in Aug 14 [2].
Aug 12ViiV Healthcare and GlaxoSmithKline initiate a PIIb dose-ranging trial of oral cabotegravir to evaluate efficacy and tolerability (NCT01641809). During the induction phase, cabotegravir (10 - 60mg) will be administered in combination with nucleoside reverse transcriptase inhibitors (lamivudine/abacavir or emtricitabine/tenofovir disoproxil fumarate). This will be followed by the maintenance phase where cabotegravir will be administered in combination with rilpivirine. A total of 244 patients have been recruited in the US and Canada [2].

Evidence based evaluations

Vocabria (EU, US) Short-term treatment of HIV infection in adults virologically suppressed on a stable antiretroviral regimen for oral lead in to assess tolerability prior to administration of long acting injection, or who will miss planned dosing with cabotegravir injection plus rilpivirine injection

Information

Vocabria (EU, US)
New formulation
ViiV Healthcare
Janssen

Development and Regulatory status

Launched
Approved (Licensed)
Approved (Licensed)
October 2021
Oct 21Available in the UK. Price 1 x 30x30mg Tablets = £638.57. [7,8].
Jan 21FDA approves Vocabria (cabotegravir, tablet formulation), which should be taken in combination with oral rilpivirine (Edurant) for one month prior to starting treatment with Cabenuva to ensure the medications are well-tolerated before switching to the extended-release injectable formulation [6].
Dec 20Approved in the EU (and UK). Has also been filed in the US [2].
Oct 20EU CHMP issues a positive opinion for in combination with rilpivirine tablets for the short-term treatment of Human Immunodeficiency Virus type 1 (HIV-1) infection in adults who are virologically suppressed (HIV-1 RNA <50 copies/mL) on a stable antiretroviral regimen without present or past evidence of viral resistance to, and no prior virological failure with agents of the NNRTI and INI class for: oral lead in to assess tolerability of Vocabria and rilpivirine prior to administration of long acting cabotegravir injection plus long acting rilpivirine injection; and oral therapy for adults who will miss planned dosing with cabotegravir injection plus rilpivirine injection [2].
Jul 19Filed in the EU [2].

Category

HIV integrase inhibitor
The UK has a relatively small, concentrated HIV epidemic, with an estimated 101,600 people living with HIV in 2017. This translates into an HIV prevalence of 1.7 per 1,000 people of all ages or 2.2 per 1,000 of people aged 15-74 years [1].
Short-term treatment of HIV infection in adults virologically suppressed on a stable antiretroviral regimen for oral lead in to assess tolerability prior to administration of long acting injection, or who will miss planned dosing with cabotegravir injection plus rilpivirine injection
Oral

Further information

Yes

Trial or other data

Aug 20PII LATTE-2 study continues to follow-up patients in the US, Canada, France, Germany and Spain. Due to complete Feb 22 [5].
Jan 20Results posted for PII LATTE study [5].
Jan 19PII LATTE study completes [5].
Jul 17Results of PIIb trial NCT02120352 (LATTE-2) published in The Lancet. RCT (n=286) reports that at 32 weeks follow-up, the two-drug combination of all-injectable, long-acting cabotegravir plus rilpivirine every 4 weeks or every 8 weeks was as effective as daily three-drug oral therapy at maintaining HIV-1 viral suppression [4].
Aug 12ViiV Healthcare and GlaxoSmithKline initiate the PIIb LATTE dose-ranging trial of oral cabotegravir to evaluate efficacy and tolerability (NCT01641809). During the induction phase, cabotegravir (10 - 60mg) will be administered in combination with nucleoside reverse transcriptase inhibitors (lamivudine/abacavir or emtricitabine/tenofovir disoproxil fumarate). This will be followed by the maintenance phase where cabotegravir will be administered in combination with rilpivirine. A total of 244 patients have been recruited in the US and Canada [2,3].

Evidence based evaluations

Vocabria (EU,US)Long acting injection for pre-exposure prophylaxis of HIV

Information

Vocabria (EU,US)
Licence extension / variation
ViiV Healthcare
Janssen

Development and Regulatory status

None
None
Pre-registration (Filed)
Sep 21FDA grants priority review with a target approval date of 24 January 2022. [14]
May 21ViiV Healthcare initiates rolling submission of new drug application with US FDA for long-acting cabotegravir for prevention of HIV
Nov 20Granted breakthrough therapy designation (BTD) in US [10]
Jan 19Still in PIII trials which are due to complete in Q1 2022.[6,7]
Mar 17PIII [1].

Category

HIV integrase inhibitor
Of those receiving HIV care in 2017, 43,494 (47%) were exposed to HIV through sex between men, 43,141 (46%) were exposed through sex between a man and a woman, 1,900 (2%) were exposed through injecting drug use, and 1,664 through vertical transmission or via medical blood products (<2%).[5]
Long acting injection for pre-exposure prophylaxis of HIV
Intramuscular

Trial or other data

Aug 21PIII HPTN 083 RCT (n=1698 in US) stopped early for efficacy reports long-acting injectable cabotegravir (600mg IM 8 weekly) was superior to daily oral tenofovir disoproxil fumarate–emtricitabine (TDF–FTC) in preventing HIV infection in this population (HR 0.34; 95 CI, 0.18 to 0.62) [13].
Nov 20Interim analysis of the HPTN 084 trial (n=3223) shows CAB LA given 2-monthly is 89% more effective (95% CI 68%-96%) in preventing HIV acquisition in women who are at increased risk of HIV acquisition vs. daily oral emtricitabine/tenofovir disoproxil fumarate 200 mg and 300 mg (FTC/TDF) tablets. The study achieved its primary objective of demonstrating superiority when compared to current SOC. Pts taking emtricitabine/ tenofovir disoproxil fumarate 200 mg and 300 mg (FTC/TDF) tablet arm will be offered CAB LA [11].
Jul 20Final data presented from the PIIb/III HPTN-083 randomised, double-blind, trial that is evaluating the safety and efficacy of long-acting, injectable cabotegravir vs. Truvada for HIV pre-exposure prophylaxis (PrEP) among men who have sex with men (MSM) and transgender women who have sex with men. There were 52 HIV cases; 13 in the long-acting cabotegravir arm and 39 in the daily Truvada arm (HIV contraction rates of 0.41% vs. 1.22% respectively). Data will be used to support filing. [9]
May 20Interim analysis of the HPTN 083 trial (n= ~4600) shows long-acting injectable cabotegravir (CAB LA) given 2-monthly is 69% more effective (95% CI 41%-84%) in preventing HIV acquisition in men who have sex with men (MSM) and transgender women who have sex with men vs. daily oral emtricitabine/tenofovir disoproxil fumarate 200 mg and 300 mg (FTC/TDF) tablets. The study achieved its primary objective of non-inferiority with the difference approaching superiority in favour of cabotegravir, pending final analysis. Pts taking emtricitabine/ tenofovir disoproxil fumarate 200 mg and 300 mg (FTC/TDF) tablet arm will be offered CAB LA.[8]
Jan 19PIII HPTN 084 study (NCT03164564) still recruiting. The HIV incidence rate [primary efficacy outcome measure) will be calculated as the total number of pts with confirmed incident HIV infection during study follow-up of Step 1 (48 wks) and Step 2 [to 81 weeks] divided by the person-years accumulated in each arm. The study has an estimated primary completion date of March 22.[7]
Jan 19 PII/III study (NCT02720094) is still recruiting. The primary efficcay outcome measure will be; no. of HIV infections in Steps 1 and 2 [last study visit and up to 4.5 years after study entry]. The study has an estimated primary completion date of March 22.[6]
Nov 17ViiV Healthcare initiate PIII study of efficacy of long-acting cabotegravir for prevention of HIV infection in sexually active women. HPTN 084 study will recruit ~3200 women from sub-Saharan Africa and assess injections of long-acting cabotegravir given every 2 months compared with daily oral PEP with Truvada [4].
Aug 17 ViiV Healthcare is anticipating a second PIII trial to assess the long-acting cabotegravir for prevention of HIV infection in young women in 2017 [2].
Dec 16PII/III safety and efficacy study of cabotegravir tablets compared with daily, oral tenofovir disoproxil fumarate/emtricitabine for pre-exposure prophylaxis in HIV-infected cisgender men and transgender women who have sex with men start (NCT02720094). The trial will enrol approximately 4,500 patients in the US, Thailand, South America, Asia and Africa [2].