The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has issued a positive opinion recommending marketing authorisation for ViiV Healthcare’s Vocabria (cabotegravir injection and tablets) in combination with Janssen’s Rekambys (rilpivirine injection) and Edurant (rilpivirine tablets) for treatment of HIV.
The regimen is for the treatment of Human Immunodeficiency Virus type 1 (HIV-1) infection in adults who are virologically suppressed (HIV-1 RNA less than 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 non-nucleoside reverse transcriptase inhibitor (NNRTI) and integrase inhibitor (INI) class.[i]
If approved, cabotegravir injection used in combination with rilpivirine injection will be the first complete long-acting regimen, dosed once-monthly or once every 2-months, for virologically suppressed people living with HIV-1 across Europe. This treatment will offer people living with HIV an option with significantly less frequent dosing and comparable efficacy to daily oral regimens. Cabotegravir and rilpivirine injections are administered as two intramuscular (IM) injections in the buttocks during the same visit at a specialist clinic by a healthcare professional. Prior to the initiation of the injections, cabotegravir and rilpivirine oral tablets are taken for approximately one month (at least 28 days) to assess tolerability to the medicines.
The Marketing Authorisation Application (MAA) for cabotegravir injection and tablets is based on the pivotal phase III ATLAS (Antiretroviral Therapy as Long-Acting Suppression), FLAIR (First Long-Acting Injectable Regimen) and ATLAS-2M studies.
The ATLAS and FLAIR studies included more than 1,100 participants from 16 countries.[ii],[iii] The studies demonstrated that cabotegravir and rilpivirine when injected intramuscularly in the buttocks, once-monthly, was as effective as continuing their daily, oral, antiretroviral regimens in maintaining viral suppression throughout the 48-week study period. The long-acting regimen was preferred by approximately 9 out of 10 patients who switched to cabotegravir and rilpivirine long-acting in the ATLAS and FLAIR studies over their previous daily oral therapy.*
In both studies, the most common adverse reactions (Grades 1 to 4) observed in ≥ 2% of participants receiving cabotegravir and rilpivirine were injection site reactions, pyrexia, fatigue, headache, musculoskeletal pain, nausea, sleep disorders, dizziness, rash, and diarrhoea. Over the 48-week study period, a total of 4% of participants discontinued cabotegravir and rilpivirine due to adverse events.[iv]
48-week data from the pivotal ATLAS-2M study were also included in the MAA to support the use of cabotegravir and rilpivirine once every 2-months. Results from the study showed the antiviral activity and safety of long-acting cabotegravir and rilpivirine injections administered once every 2-months was non-inferior to long-acting cabotegravir and rilpivirine injections administered once-monthly in virologically suppressed adults living with HIV-1 infection over a 48-week period. In the ATLAS-2M study rates of serious adverse events (SAEs) (27/522 [5.2%]) and withdrawals due to adverse events (AEs) (12/522 [2.3%]) at 48 weeks were low and were similar to those experienced in the one month arm (SAEs: 19/523 [3.6%], withdrawals due to AEs 13/523 [2.5%]).[v]
The Patient Reported Outcomes data from the ATLAS-2M study showed high levels of treatment satisfaction and acceptance,* with 98% (n=300/306) of participants who were randomised to receive an oral lead-in followed by once every 2-months dosing preferring treatment once every 2-months compared to daily oral treatment (oral lead-in). Results indicate that administration frequency and convenience were the most common reasons for preferring treatment every 2-months.
Deborah Waterhouse, CEO, ViiV Healthcare, said: “Today’s positive CHMP opinion marks an important step in providing a new option that changes the treatment experience for people living with HIV across Europe. Vocabria injection used in combination with Rekambys has the potential to ease the day-to-day burden of HIV by offering significantly less frequent dosing from 365 days with oral regimens to 12 or 6 treatments per year. Through our innovative R&D, we are now one step closer to offering an HIV medicine in Europe with a novel route of administration and dosing schedule compared to other therapies. We’re proud to be providing different treatment options that meet the diverse needs of the HIV community.”
* At Week 48, 98% of 306 patients with no prior exposure to cabotegravir or rilpivirine responded to the questionnaire preferred every 2-month injections vs 1% of 306 patients who preferred the study daily oral lead-in (1% reported no preference).
- The results are descriptive in nature and should not be used to infer clinical significance. Results are descriptive and reflect preferences shown by those entering into clinical trials of long-acting therapy. They do not imply that PLHIV in general would prefer long-acting therapy
- In the pooled exploratory analysis in the ITT-E population: patients responded to the preference question at Week 48 (59 patients did not). 88% (523/591) preferred cabotegravir and rilpivirine long-acting vs. 2% (9/591) who preferred their previous daily oral therapy.
- Patient preference data is collected from clinical trial participants randomised to long-acting arm, completing a single-item question assessing their preference for cabotegravir and rilpivirine long acting compared to daily oral ART medication they were receiving prior to entry in the ATLAS and FLAIR studies
[ii] Swindells S, Andrade-Villanueva J-F, Richmond G, et al. Long-acting cabotegravir and rilpivirine for maintenance of HIV-1 suppression. N Engl J Med. DOI: 10.1056/ NEJMoa1904398.
[iii] Orkin C, Arasteh K, Hernandez-Mora MG, et al. Long-acting cabotegravir and rilpivirine after oral induction for HIV-1 infection. N Engl J Med. DOI: 10.1056/ NEJMoa1909512.
[iv] Overton ET, Orkin C, Swindell S, et al. Monthly long-acting cabotegravir and rilpivirine is non-inferior to oral ART as maintenance therapy for HIV-1 infection: Week 48 pooled analysis from the phase 3 ATLAS and FLAIR studies. Presented at IAS 2019.
[v] Overton ET et. al. Cabotegravir and rilpivirine every 2 months is non inferior to monthly: ATLAS-2M study. Presented at CROI 2020: Available at: https://www.croiconference.org/abstract/cabotegravir-rilpivirine-every-2-months-is-noninferior-to-monthly-atlas-2m-study/