ViiV Healthcare announces new data on efficacy of long-acting injectable cabotegravir for PrEP over daily, oral TDF/FTC tablets

— No new HIV infections were observed in participants who initiated cabotegravir injections in the year following study unblinding
— No birth defects reported among women who became pregnant after exposure to initial injections of cabotegravir for PrEP

London, July 28, 2022 – ViiV Healthcare, the global specialist HIV company majority-owned by GSK, with Pfizer and Shionogi as shareholders, today announced new efficacy and safety findings from the unblinded period of the HIV Prevention Trials Network (HPTN) 084 trial evaluating cabotegravir long-acting (LA) for pre-exposure prophylaxis (PrEP) in women in sub-Saharan Africa. The findings showed that cabotegravir LA for PrEP continued to demonstrate superior efficacy in the prevention of new HIV infections among women when compared to daily oral emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) tablets, with an 89% lower rate of HIV acquisition (HR 0.11, 95% CI 0.05, 0.24). Results were presented today at the 24^th International AIDS Conference (AIDS 2022) in Montreal, Canada.

The blinded phase of HPTN 084, during which participants were not told which regimen they were taking, was stopped in November 2020 by an independent data safety monitoring board after a planned interim review indicated that cabotegravir LA for PrEP had demonstrated superiority in the prevention of HIV in women when compared to daily, oral FTC/TDF tablets.

Participants were subsequently told which regimen they were taking (unblinded) and continued on their original randomised study regimen, pending a study amendment to offer open-label cabotegravir LA for PrEP to all participants who wished to take it. The data presented at AIDS 2022 include the 12-month period after HPTN 084 trial participants were unblinded, but prior to the amendment.

During the unblinded period of HPTN 084, no new cases of HIV infection occurred in participants in the cabotegravir arm of the trial, after injections were initiated. Twenty-three incident infections were observed (HIV incidence, 0.84%; 95% CI, 0.53-1.26), with three in the cabotegravir LA group (incidence, 0.22%; 95% CI, 0.04-0.63), including two who had never received an injection, and one individual who had acquired HIV before her initial cabotegravir injection, during the blinded phase of the study; and 20 in the FTC/TDF group (incidence, 1.48%; 95% CI, 0.9-2.2). Overall, 62 incident HIV infections (6 CAB, 56 TDF/FTC) have been observed over 6626 person-years of follow up (HIV incidence 0.94%, 95% CI 0.72, 1.20).

Kimberly Smith, M.D., MPH, Head of Research & Development at ViiV Healthcare, said: “These remarkable data reaffirm the potential use of long-acting cabotegravir as an effective HIV prevention option for women, particularly women in sub Saharan Africa who are disproportionately impacted by HIV. This study also continues to provide us with valuable information about women who become pregnant while receiving cabotegravir LA. Women tell us they need more choices for HIV prevention. We believe that having an alternative to a daily pill to prevent HIV that reduces dosing days from 365 to as few as six times per year can potentially have a significant impact on efforts to end the epidemic.”

New pregnancy safety data were also presented at AIDS 2022. During the unblinded phase of the HPTN 084 study, 83 confirmed pregnancies (43 on cabotegravir, 40 on TDF/FTC) occurred. Women with confirmed pregnancies while on long-acting cabotegravir for PrEP discontinued cabotegravir injections until cessation of breast feeding. No birth defects were reported in either arm of the study. The increased pregnancy incidence during the unblinded period of the study highlights the importance of ongoing studies to evaluate the safety and pharmacology of cabotegravir LA during pregnancy and lactation.

Sinead Delany-Moretlwe, MBBCh, Ph.D., DTM&H, HPTN 084 protocol chair, and research director at Wits RHI, University of the Witwatersrand in Johannesburg, South Africa, said: “The latest findings from the HPTN 084 trial underscore the significant impact that cabotegravir LA for PrEP can have for the prevention of HIV in women, especially in resource-limited settings like sub-Saharan Africa where the study was conducted. Young women in this region bear a disproportionate burden of the epidemic and may be twice as likely as their male counterparts to contract HIV. If we are to successfully end the HIV epidemic, the availability of new HIV prevention options like cabotegravir LA for PrEP will be critical for ensuring an impact on HIV incidence in populations at greatest need.”

Cabotegravir LA for PrEP continued to be well-tolerated throughout the study, with no new safety concerns identified during the 12-month unblinded period. Grade 2 injection site reactions (ISRs) were low in the cabotegravir arm (2.4%). Overall, Grade 2 adverse events were comparable between study groups, with 20% assessed as related to study product (19% for cabotegravir arm, 21% for FTC/TDF arm).

Cabotegravir LA for PrEP is currently approved in the U.S. as Apretude. It is approved for use in adults and adolescents weighing at least 35 kg who are at risk of sexually acquiring HIV and who have a negative HIV-1 test prior to initiation. ViiV Healthcare has initiated submissions to other regulatory authorities. Apretude has not yet been approved or licensed anywhere outside of the U.S. for use in HIV prevention.

About cabotegravir extended-release injectable suspension
Cabotegravir LA for PrEP is an integrase strand transfer inhibitor (INSTI). INSTIs, like cabotegravir extended-release injectable suspension, inhibit HIV replication by preventing the viral DNA from integrating into the genetic material of human immune cells (T-cells). This step is essential in the HIV replication cycle and is also responsible for establishing chronic disease.

Cabotegravir LA for PrEP is provided as an injection given as few as six times per year and is initiated with a single 600 mg (3-ml) intramuscular injection given one month apart for two consecutive months. After the second initiation injection, the recommended continuation injection dose is a single 600 mg (3-ml) injection given every two months. Vocabria (cabotegravir oral tablets) may be administered for approximately one month before initiating the first injection to assess the tolerability of the medicine.

Trademarks are owned by or licensed to the ViiV Healthcare group of companies.

About HPTN 084 (NCT03164564)

The HPTN 084 trial is a phase III double blind superiority trial designed to evaluate the safety and efficacy of the cabotegravir LA for HIV prevention administered every eight weeks compared to daily oral FTC/TDF tablets (200 mg/300 mg) in 3,224 cisgender women who are at increased risk of HIV acquisition. The trial design included an oral lead-in phase to assess tolerability to cabotegravir before administering the IM injection. HPTN 084 opened to enrolment in November 2017 and is being conducted at research centres in Botswana, Kenya, Malawi, South Africa, Eswatini, Uganda, and Zimbabwe.

Cabotegravir LA was found to be superior to daily oral FTC/TDF in preventing HIV acquisition in the trial population. The most common adverse reactions (all grades) observed in at least 1% of subjects receiving cabotegravir LA were injection site reactions, diarrhoea, headache, fatigue, sleep disorders, nausea, dizziness, abdominal pain, vomiting, myalgia, and rash.

HPTN 084 was jointly funded by the U.S. National Institute of Allergy and Infectious Diseases (NIAID), and the National Institute of Mental Health (NIMH), the Bill & Melinda Gates Foundation and ViiV Healthcare, and was conducted by the HPTN. Study product was provided by ViiV Healthcare and Gilead Sciences. For further information please see https://clinicaltrials.gov/ct2/show/NCT03164564.

About ViiV Healthcare

ViiV Healthcare is a global specialist HIV company established in November 2009 by GlaxoSmithKline (LSE: GSK) and Pfizer (NYSE: PFE) dedicated to delivering advances in treatment and care for people living with HIV and for people who are at risk of becoming infected with HIV. Shionogi joined as a shareholder in October 2012. The company’s aims are to take a deeper and broader interest in HIV and AIDS than any company has done before and take a new approach to deliver effective and innovative medicines for HIV treatment and prevention, as well as support communities affected by HIV.

For more information on the company, its management, portfolio, pipeline, and commitment, please visit www.viivhealthcare.com.

About GSK

GSK is a global biopharma company with a purpose to unite science, technology, and talent to get ahead of disease together. Find out more at gsk.com/company.