LONDON—ViiV Healthcare, the global specialist HIV company majority owned by GlaxoSmithKline (GSK), with Pfizer Inc. and Shionogi Ltd. as shareholders, recently presented positive long-term data from its global phase 3b ATLAS-2M study of what is said to be the first complete, long-acting regimen of cabotegravir and rilpivirine for the treatment of HIV.
Week 96 findings reinforce the primary (proportion of participants with plasma HIV-1 RNA ≥50 c/mL at week 48 (Snapshot, ITT-E)), and secondary endpoints (proportion of participants with plasma HIV-1 RNA ≥50 or <50 c/mL at week 96 (Snapshot, ITT-E)), initially assessed at week 48, and now showing efficacy of both monthly dosing and every two-month dosing over the long term in virologically supressed adults with HIV-1.
These data were presented at the virtual Conference on Retroviruses and Opportunistic Infections (CROI 2021). The every-two-month dosing regimen of cabotegravir and rilpivirine is under investigation and not approved in the United States or Canada.
“The ATLAS-2M 96-week data reinforces the therapeutic potential of this long-acting regimen for the treatment of HIV. It provides an option that could change the treatment experience for some people living with HIV by removing the need for daily pills for the treatment of HIV," said Dr. Hans Jäeger, former medical director of MVZ Karlsplatz, HIV Research and Clinical Care Centre, Munich, and investigator for the ATLAS-2M study. "Taking a pill every day can come as an unwelcome daily reminder of their HIV status or it may add to their fears that their HIV status might be disclosed by someone seeing their HIV medication. This regimen can enable people living with HIV to reduce the days they receive treatment from 365 to 12 or 6 per year, representing a paradigm shift in their experience of HIV treatment.”
Added Dr. Kimberly Smith, head of Research & Development at ViiV Healthcare: “At ViiV Healthcare, our research and development is underpinned by a commitment to innovation and a desire to make a difference to the lives of people living with HIV. Long-acting cabotegravir and rilpivirine is a first-of-its-kind regimen that removes the need for daily therapies after the initiation phase. These long-term data confirm that every-two-month dosing is non-inferior to monthly dosing, which means people living with HIV who are virologically supressed can reduce the number of days they take treatment to sixtimes per year, allowing more time between doses with this regimen.”
ATLAS-2M met its primary endpoint at week 48, demonstrating that the efficacy of long-acting cabotegravir and rilpivirine dosed every eight weeks was non-inferior to monthly dosing (every four weeks). Week 48 primary endpoint (proportion of participants with plasma HIV-1 RNA ≥50 c/mL) results showed every 2-month dosing (9/522 [1.7%]) and monthly dosing (5/523 [1.0%]) were similarly effective (adjusted difference: 0.8%, 95% confidence interval [CI]: -0.6, 2.2).
Week 96 findings reinforced the primary endpoint: the efficacy of the two-month dosing was non-inferior to monthly dosing of long-acting cabotegravir and rilpivirine, with 2.1% (11/522) and 1.1% (6/523) of participants, respectively, having HIV-1 RNA ≥50 c/mL (adjusted difference: 1.0%, 95% CI: -0.6-2.5).1 The 96-week ATLAS-2M study secondary endpoint, showed that rates of virologic suppression were similar between the two arms, with 91.0% (475/522) of participants in the every 2-month dosing arm and 90.2% (472/523) in the monthly dosing arm achieving HIV-1 RNA <50 c/mL (adjusted difference: 0.8%, 95% CI: -2.8-4.3).
Week 96 findings reported confirmed virologic failures (CVFs), defined as two consecutive viral loads ≥200 c/mL, in 1.7% (9/522) of participants in the every 2-month dosing arm and 0.4% (2/523) in the monthly dosing arm. The rate of CVF was low overall [1% ( 11/1,045], with only one participant in the every 2-month dosing arm meeting the criterion in the second year of therapy. This patient developed a rilpivirine resistance-associated mutation (RAM) Y181C, and no integrase inhibitor (INSTI) RAMS.
Safety profiles were comparable between the two treatment arms, with no new safety signals identified since the 48-week analysis.1,2 Injection site reactions (ISRs) were the most common adverse events (AE) (16% [74/473] in the every 2-month dosing arm and 12% [54/468] in the monthly dosing arm), with one leading to withdrawal between weeks 48 and 96.1 Most ISRs (99%) were mild or moderate and self-resolving, with a median duration of three days. Over the entire 96 weeks, in the every-two-month dosing arm, 1% (7/522) of participants discontinued due to ISRs, vs 2% (11/523) in the monthly dosing arm.
The most common non-injection site reactions drug-related AEs were pyrexia and fatigue. Grade ≥ 3 adverse events were seen in 11% (57/522) of participants in the every 2-month arm and 12% (65/523) in the once monthly arm. Adverse events leading to withdrawal were seen in 3% (18/522) of participants in the every 2-month arm and 4% (19/523) in the monthly arm.
ViiV Healthcare’s cabotegravir in combination with Janssen’s rilpivirine was co-developed as part of a collaboration with Janssen and builds on ViiV Healthcare’s industry-leading portfolio that is centered on delivering innovative medicines for the HIV community.
The long-acting regimen of cabotegravir and rilpivirine is licensed as a once-monthly treatment in Canada and the United States under the brand name Cabenuva. A supplemental New Drug Application has been submitted to the FDA for expanding the use of Cabenuva as an HIV treatment to include use of every-two-month dosing in the US. Cabenuva is listed in Australia for both monthly and every-two-month dosing. The long-acting regimen has also received Marketing Authorisation under the brand names Vocabria (cabotegravir) and Rekambys (rilpivirine) in Europe for both forms of dosing. Further regulatory applications have been submitted and are being reviewed by other regulatory bodies worldwide.