GlaxoSmithKline : ViiV Healthcare announces start of implementation science study to identify and evaluate approaches to integrating its investigational, every-two-month, injectable HIV treatment in European healthcare practices

For media and investors only

Issued: London, UK

ViiV Healthcare, the global specialist HIV company majority owned by GSK, with Pfizer Inc. and Shionogi Limited as shareholders, today announced the start of the CARISEL study (Cabotegravir And Rilpivirine Implementation Study in European Locations), which aims to evaluate the best approaches to implementing an investigational, every-two-month, injectable HIV treatment regimen into clinical practice in Europe.

A team from ViiV Healthcare will work with clinical staff at 18 diverse practice sites across different healthcare systems in France, Spain, Belgium, Germany, and the Netherlands during the one-year study, in which healthcare providers and patients will play an equally important role. The goal is to find the most practical and efficient ways to implement an injectable treatment regimen administered every two months, including how to address the need for increased frequency of clinic visits to administer the regimen.

Dr. Laurent Hocqueloux, CARISEL investigator from Orléans's Hospital in France, said: 'We're excited that people living with HIV may have the option to replace daily pills with a long-acting injectable regimen. If approved, this change means they will need to receive injections from a healthcare provider and visit their physicians more frequently. The CARISEL trial will help generate data to help prepare medical practices for the changes to current practices that may be needed as a result of this new regimen. It will also guide us as we incorporate this novel approach into a variety of health systems in Europe, where differences may emerge from country to country in how clinical practices allocate personnel, prescribe the treatment, and administer it to people living with HIV.'

CARISEL will be enrolling approximately 450 people living with HIV and 54 clinical staff members to take part in the two components of the study. Patient study participants will take part in a single-arm study where they will receive the long-acting regimen of cabotegravir and rilpivirine dosed every two months and complete surveys and interviews that capture their perspectives towards the feasibility, acceptability, and appropriateness of the regimen.

Staff study participants will participate in a two-arm study examining different implementation strategies to support potential barriers around factors including, but not limited to: medication storage, appointment scheduling, and patient support. Both arms will have access to toolkits aimed to support education and proper treatment administration, as well as injection training. Similar to patient study participants, staff study participants will complete surveys and interviews with investigators.

The CARISEL study is part of ViiV Healthcare's pioneering Implementation Science programme, focusing on improving the real-world delivery of HIV treatment and care outside the structured environment of clinical trials. Implementation science trials led by ViiV Healthcare are ongoing globally to study a variety of issues including improving access to testing, clinical care and effective treatment. In October, ViiV Healthcare will be completing the final study visits for the CUSTOMIZE study, the eight-site US companion to CARISEL, which focused on identifying and evaluating approaches to implementing the once-monthly, injectable treatment for HIV into clinical practice.

Harmony P. Garges, M.D., MPH, Chief Medical Officer at ViiV Healthcare, said: 'Implementation research through studies like CARISEL and CUSTOMIZE helps us take the scientific innovation we've achieved in clinical trials and best apply it to our real-world efforts to improve the care of people living with HIV. CARISEL will allow us to tailor strategies and create materials to match the specific needs of different clinical settings in Europe and builds on the positive body of evidence we've already seen from US practices in the companion study CUSTOMIZE. ViiV Healthcare is proud to lead the industry in HIV implementation science and we look forward to sharing these findings in the future.'

The initial results of the CARISEL study, which is studying the twice-monthly, long-acting regimen of cabotegravir and rilpivirine, are anticipated in 2021. The once-monthly long-acting regimen of cabotegravir and rilpivirine was approved by Health Canada in March 2020 under the brand name CABENUVA and is currently under review by the US Food and Drug Administration (FDA), European Medicines Agency (EMA) and other global regulatory authorities.

About the CARISEL study

CARISEL is an open-label, hybrid type phase IIIb trial evaluating implementation strategies for long‐acting cabotegravir and rilpivirine administered every two months in select European healthcare settings. It is a single-arm, multicentre, interventional study for patient participants and a two-arm, multicentre, non-interventional study for clinical staff participants, with the goal of evaluating the effect of implementation strategies on the degree of acceptability, appropriateness and feasibility of clinic practices to deliver the every-two-months, injectable regimen of cabotegravir and rilpivirine to people living with HIV. The study will evaluate both qualitative and quantitative measures across arm, clinic type, provider type, and country to determine the most effective implementation strategies and to identify barriers, facilitators, and solutions. In addition to findings on its implementation, clinical data on the efficacy and safety of cabotegravir and rilpivirine will be evaluated.

About the long-acting regimen of cabotegravir and rilpivirine

The long-acting regimen of cabotegravir and rilpivirine is an investigational regimen for the treatment of HIV-1 infection in adults to replace the current antiretroviral regimen in patients who are virologically stable and suppressed (HIV-1 RNA less than 50 copies/mL). The complete regimen combines the integrase strand transfer inhibitor (INSTI) cabotegravir, developed by ViiV Healthcare, with rilpivirine, a non-nucleoside reverse transcriptase inhibitor (NNRTI) developed by Janssen Sciences Ireland UC.

INSTIs, like cabotegravir, 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 infection. Rilpivirine is an NNRTI that works by interfering with an enzyme called reverse transcriptase, which in turn stops the virus from multiplying.

Important Safety Information for CABENUVA

Indications and clinical use:

CABENUVA (cabotegravir and rilpivirine extended release injectable suspensions) is indicated as a complete regimen for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in adults to replace the current antiretroviral regimen in patients who are virologically stable and suppressed (HIV-1 RNA <50 copies/mL).

VOCABRIA (cabotegravir tablets) is indicated, in combination with EDURANT (rilpivirine tablets), as a complete regimen for short-term treatment of human immunodeficiency virus type 1 (HIV-1) infection in adults who are virologically stable and suppressed (HIV-1 RNA <50 copies/mL) as: An oral lead-in to assess tolerability of cabotegravir prior to initiating CABENUVA

Oral bridging therapy for missed CABENUVA injections

• Geriatrics (>65 years of age): Not sufficiently studied to determine if they respond differently than patients <65 years of age
• Pediatrics (<18 years of age): Safety and efficacy not established

Contraindications:

In combination with:

• Anticonvulsants: Carbamazepine, oxcarbazepine, phenobarbital, and phenytoin
• Antimycobacterials: Rifabutin, rifampin, rifapentine
• Glucocorticoid: Systemic dexamethasone (more than a single dose)
• St John's wort (Hypericum perforatum)

Relevant warnings and precautions:

• Should not be used in patients with known or suspected resistance to cabotegravir or rilpivirine
• Patients may still develop opportunistic infections and other complications of HIV infection
• Risk of transmission: precautions should be taken
• Depressive disorders
• Hepatotoxicity (serum transaminase elevations)
• Hepatic adverse events; increased risk for worsening or development of transaminase elevations in patients with hepatitis B or C co-infection or marked elevations in transaminases prior to treatment; monitoring of liver chemistries is recommended
• Loss of virologic response due to drug interactions; review concomitant medications during therapy
• Caution when used in combination with drugs that have a risk of Torsade de Pointes
• Skin and hypersensitivity reactions; discontinue immediately if signs or symptoms develop
• Administer the oral lead-in dosing prior to administration of CABENUVA to help identify patients who may be at risk of a hypersensitivity reaction
• Residual concentrations of cabotegravir and rilpivirine injections may remain in the systemic circulation of patients for up to 12 months or longer
• Risk of resistance due to treatment discontinuation
• Post-injection reactions within minutes after the injection of rilpivirine, including dyspnea, agitation, abdominal cramping, flushing, sweating, oral numbness, and changes in blood pressure. Reported in <0.5% of subjects and began to resolve minutes after the injection, and may have been associated with inadvertent (partial) IV administration
• Insufficient data in pregnant women; should not be used unless the potential benefits outweigh the potential risks
• HIV-1-infected mothers should not breastfeed their infants if receiving CABENUVA

For more information:

Please consult the Product Monograph at cabenuvapm.viivhealthcare.ca for additional important information relating to adverse reactions, drug interactions, and dosing. The Product Monograph is also available by calling 1-877-393-8448. To report an adverse event, please call 1-877-393-8448.

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 in October 2012. The company's aim is to take a deeper and broader interest in HIV/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 science-led global healthcare company with a special purpose: to help people do more, feel better, live longer. For further information please visit www.gsk.com/about-us.

Cautionary statement regarding forward-looking statements

GSK cautions investors that any forward-looking statements or projections made by GSK, including those made in this announcement, are subject to risks and uncertainties that may cause actual results to differ materially from those projected. Such factors include, but are not limited to, those described under Item 3.D 'Risk Factors' in the company's Annual Report on Form 20-F for 2019 and any impacts of the COVID-19 pandemic.