VIIV HEALTHCARE ANNOUNCES POSITIVE DATA DEMONSTRATING LONG-ACTING INJECTABLE CABENUVA (CABOTEGRAVIR, RILPIVIRINE) IS AS EFFECTIVE AS DAILY ORAL BIKTARVY (BIC/FTC/TAF) FOR THE TREATMENT OF HIV-1

London, 23 February 2023 – ViiV Healthcare, the global specialist HIV company majority owned by GSK, with Pfizer and Shionogi as shareholders, announced yesterday positive 12-month findings from the SOLAR study. SOLAR is the first head-to-head, Phase IIIb study of the first and only complete long-acting injectable regimen Cabenuva (cabotegravir, rilpivirine [CAB+RPV LA]) compared against complete daily oral regimen Biktarvy (bictegravir/emtricitabine/tenofovir alafenamide [BIC/FTC/TAF]).

Study findings showed that CAB+RPV LA dosed every two months achieved the primary endpoint of non-inferior virologic efficacy versus daily oral BIC/FTC/TAF, while 90% of participants who switched to CAB+RPV LA from BIC/FTC/TAF, and who completed a survey (n=425), preferred the long-acting regimen. Switching to CAB+RPV LA from BIC/FTC/TAF during the SOLAR study was efficacious, well-tolerated, and improved treatment satisfaction from baseline based on adjusted HIV Treatment Satisfaction Questionnaire status version scores (HIVTSQs). These data were presented at the 30^th Conference on Retroviruses and Opportunistic Infections (CROI), being held in Seattle, Washington.

Harmony P. Garges, M.D., MPH, Chief Medical Officer at ViiV Healthcare, said: “The treatment needs of people living with HIV are changing, with ample evidence on patient preference suggesting some people living with HIV can experience challenges with taking daily oral treatment for HIV. It’s essential that people living with HIV have treatment options that can help alleviate these burdens and we believe that complete long-acting regimens are here to help address some of those challenges today. We are confident that cabotegravir, as part of a complete long-acting regimen, is a cornerstone for the long-acting treatment era in HIV medicine, as supported by its strong and durable efficacy, safety, and by the fact that 90% of participants in this study who completed a survey preferred a long-acting regimen after switching from their daily oral pills.”

In the SOLAR study, 670 participants who were virally supressed and taking BIC/FTC/TAF were randomised 2:1 to switch to CAB+RPV LA administered every two months (447 participants) or continue taking daily oral BIC/FTC/TAF (223 participants). The SOLAR study met its primary endpoint at Month 12, when CAB+RPV LA demonstrated non-inferior efficacy versus daily oral BIC/FTC/TAF based on the proportion of participants with HIV-1 RNA ≥50 c/mL using the FDA Snapshot algorithm and a 4% non-inferiority margin (mITT-E; CAB+RPV LA: 5/447 [1%], BIC/FTC/TAF: 1/223 [<1%], adjusted difference: 0.7%, 95% confidence interval [-0.7, 2.0]). The study found that rates of virologic suppression (HIV-1 RNA <50 c/mL) were similar between treatment arms (CAB+RPV LA: 403/447 [90%], BIC/FTC/TAF: 207/223 [93%], adjusted difference: -2.7%, 95% confidence interval [-7.0, 1.7]). Non-inferior virologic outcomes were confirmed in the ITT-E and Per Protocol (PP) analyses.

At the beginning of the study, 47% of participants reported always or often experiencing one or more challenges with taking their daily therapy, including “being worried about people unintentionally discovering their HIV status,” “being worried about forgetting to take their HIV medication,” or “feeling that taking their HIV medication was an uncomfortable reminder of their HIV status.” Mean treatment satisfaction scores (HIVTSQs) improved significantly at the conclusion of the study for participants taking CAB+RPV LA (+3.36) compared to BIC/FTC/TAF (-1.59) from baseline (CAB+RPV LA: 57.88, BIC/FTC/TAF: 58.38) (p<0.001). 90% of participants who switched to CAB+RPV LA and completed the survey, preferred long-acting therapy versus daily oral pills (n=382/425), with the top five reasons for preferring long-acting therapy being:

• I don’t have to worry as much about remembering to take HIV medication every day
• It is more convenient for me to receive injections every 2 months
• I do not have to carry my HIV medication with me
• I do not have to think about my HIV status every day
• I do not have to worry about others seeing or finding my HIV pills

Confirmed virologic failure (CVF) was infrequent. Two participants (0.4%) in the mITT-E analysis and one additional participant in the ITT-E analysis who received CAB+RPV LA, developed CVF, with subsequent identification of resistance-associated mutations (RAMs) to NNRTI and integrase inhibitors. No participant in the BIC/FTC/TAF treatment arm developed CVF.

Treatment with CAB+RPV LA and BIC/FTC/TAF were both well-tolerated. With the exclusion of injection site reaction (ISRs), adverse events (AEs) and serious adverse events (SAEs) were comparable between arms, although drug-related AEs were more frequent in the long-acting (the switch) arm (20% vs <1%). The most commonly reported drug-related AEs in the LA arm were pyrexia (3%), headache (2%), fatigue (2%), and diarrhoea (2%). In the BIC/FTC/TAF arm, the two drug-related AEs reported were weight gain (<1%) and abnormal hepatic function (<1%). Most ISRs in the long-acting arm were Grade 1 or 2 (98%) and short lived (median 3 days), with few participants discontinuing due to injection-related reasons (2%). More participants in the long-acting arm withdrew due to AEs (6% vs <1%).

Moti N. Ramgopal of the Midway Immunology and Research Center, Fort Pierce, Florida and Principal Investigator for SOLAR, said: “There are many people living with HIV who are virally suppressed but experience challenges taking a daily oral pill, including fears of accidentally disclosing their HIV status due to discovery of their medicine. The SOLAR findings demonstrate that CAB+RPV LA administered every two months is as effective as BIC/FTC/TAF, while also addressing some important challenges associated with taking daily HIV treatment. These findings raise the critical reminder that healthcare providers who prescribe HIV medicines should identify and incorporate patient preferences when making treatment recommendations, in addition to standard efficacy and safety data, to ensure that people living with HIV have the best treatment option for their needs.”

ViiV Healthcare’s cabotegravir in combination with rilpivirine, a product of Janssen Sciences Ireland Unlimited Company, one of the Janssen Pharmaceutical Companies of Johnson & Johnson was co-developed as part of a collaboration with Janssen and builds on ViiV Healthcare’s industry-leading long-acting portfolio that is centred on delivering innovative medicines for the HIV community. The complete long-acting regimen of CAB+RPV LA is licensed in Canada, USA and Australia under the brand name Cabenuva, and in Europe and Japan as Vocabria (cabotegravir injection and tablets) and Rekambys (rilpivirine long-acting injectable suspension). Additional findings and analyses from the SOLAR study, including additional data on patient reported outcomes, will be presented at future congresses.

CONTRAINDICATIONS

• Do not use Cabenuva in patients with previous hypersensitivity reaction to cabotegravir or rilpivirine
•  Do not use Cabenuva in patients receiving carbamazepine, oxcarbazepine, phenobarbital, phenytoin, rifabutin, rifampin, rifapentine, systemic dexamethasone (>1 dose), and St John’s wort

WARNINGS AND PRECAUTIONS

Hypersensitivity Reactions:

• Hypersensitivity reactions, including cases of Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), have been reported during postmarketing experience with rilpivirine-containing regimens. While some skin reactions were accompanied by constitutional symptoms such as fever, other skin reactions were associated with organ dysfunctions, including elevations in hepatic serum biochemistries
• Serious or severe hypersensitivity reactions have been reported in association with other integrase inhibitors and could occur with Cabenuva
• Discontinue Cabenuva immediately if signs or symptoms of hypersensitivity reactions develop. Clinical status, including liver transaminases, should be monitored and appropriate therapy initiated. Prescribe the oral lead-in prior to administration of Cabenuva to help identify patients who may be at risk of a hypersensitivity reaction

Post-Injection Reactions:

• Serious post-injection reactions (reported in less than 1% of subjects) were reported within minutes after the injection of rilpivirine, including dyspnea, bronchospasm, agitation, abdominal cramping, rash/urticaria, dizziness, flushing, sweating, oral numbness, changes in blood pressure, and pain (e.g., back and chest). These events may have been associated with inadvertent (partial) intravenous administration and began to resolve within a few minutes after the injection
• Carefully follow the Instructions for Use when preparing and administering Cabenuva. The suspensions should be injected slowly via intramuscular injection and avoid accidental intravenous administration. Observe patients briefly (approximately 10 minutes) after the injection. If a post-injection reaction occurs, monitor and treat as clinically indicated

Hepatotoxicity:

• Hepatotoxicity has been reported in patients receiving cabotegravir or rilpivirine with or without known pre-existing hepatic disease or identifiable risk factors
• Patients with underlying liver disease or marked elevations in transaminases prior to treatment may be at increased risk for worsening or development of transaminase elevations
• Monitoring of liver chemistries is recommended and treatment with Cabenuva should be discontinued if hepatotoxicity is suspected

Depressive Disorders:

• Depressive disorders (including depressed mood, depression, major depression, mood altered, mood swings, dysphoria, negative thoughts, suicidal ideation or attempt) have been reported with Cabenuva or the individual products
• Promptly evaluate patients with depressive symptoms

Risk of Adverse Reactions or Loss of Virologic Response Due to Drug Interactions:

• The concomitant use of Cabenuva and other drugs may result in known or potentially significant drug interactions (see Contraindications and Drug Interactions)
• Rilpivirine doses 3 and 12 times higher than the recommended oral dosage can prolong the QTc interval
• Cabenuva should be used with caution in combination with drugs with a known risk of Torsade de Pointes

Long-Acting Properties and Potential Associated Risks with Cabenuva:

• Residual concentrations of cabotegravir and rilpivirine may remain in the systemic circulation of patients for prolonged periods (up to 12 months or longer). Select appropriate patients who agree to the required monthly or every-2-month injection dosing schedule because non-adherence could lead to loss of virologic response and development of resistance
• To minimize the potential risk of developing viral resistance, it is essential to initiate an alternative, fully suppressive antiretroviral regimen no later than 1 month after the final injection doses of Cabenuva when dosed monthly and no later than 2 months after the final injections of Cabenuva when dosed every 2 months. If virologic failure is suspected, switch the patient to an alternative regimen as soon as possible

ADVERSE REACTIONS

• The most common adverse reactions (incidence ≥2%, all grades) with Cabenuva were injection site reactions, pyrexia, fatigue, headache, musculoskeletal pain, nausea, sleep disorders, dizziness, and rash

DRUG INTERACTIONS

• Refer to the applicable full Prescribing Information for important drug interactions with Cabenuva, VOCABRIA, or EDURANT
• Because Cabenuva is a complete regimen, coadministration with other antiretroviral medications for the treatment of HIV-1 infection is not recommended
• Drugs that are strong inducers of UGT1A1 or 1A9 are expected to decrease the plasma concentrations of cabotegravir. Drugs that induce or inhibit CYP3A may affect the plasma concentrations of rilpivirine
• Cabenuva should be used with caution in combination with drugs with a known risk of Torsade de Pointes

USE IN SPECIFIC POPULATIONS

• Pregnancy: There are insufficient human data on the use of Cabenuva during pregnancy to adequately assess a drug-associated risk for birth defects and miscarriage. Discuss the benefit-risk of using Cabenuva during pregnancy and conception and consider that cabotegravir and rilpivirine are detected in systemic circulation for up to 12 months or longer after discontinuing injections of Cabenuva. An Antiretroviral Pregnancy Registry has been established
• Lactation: The CDC recommends that HIV 1−infected mothers in the United States not breastfeed their infants to avoid risking postnatal transmission of HIV-1 infection. Breastfeeding is also not recommended due to the potential for developing viral resistance in HIV-positive infants, adverse reactions in a breastfed infant, and detectable cabotegravir and rilpivirine concentrations in systemic circulation for up to 12 months or longer after discontinuing injections of Cabenuva

Please see full Prescribing Information.

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