ViiV Healthcare presents positive data from first-ever implementation research study on how best to integrate an investigational once-monthly injectable HIV treatment in US healthcare practices

London, 4 July 2020 – ViiV Healthcare, the global specialist HIV company majority owned by GSK, with Pfizer Inc. and Shionogi Limited as shareholders, today announced positive initial findings from the CUSTOMIZE trial (Cabotegravir plus Rilpivirine in the US To Optimize and Measure Implementation and Experience), which aims to identify successful methods of implementing the investigational once-monthly, long-acting regimen of cabotegravir and rilpivirine for the treatment of HIV-1 into clinical practice.

Since the CUSTOMIZE study began, a team from ViiV Healthcare worked with physicians, nurses, clinic administrators, and patients across a range of medical practices, including federally qualified health centers, academic medical centers and private physician offices. Its goal was to find the most practical and efficient ways to implement a monthly injectable treatment regimen which, if approved, could create a paradigm shift in HIV treatment, including increasing the frequency of clinic visits from once or twice per year to every month. 

Four months into the study, the majority of clinical staff participants continued to perceive the implementation of the once-monthly injectable regimen as highly acceptable, feasible and appropriate for people living with HIV, and had a substantial decrease in what they thought would be barriers to implementation of the injectable regimen. These initial findings were presented today at the virtual 23rd International AIDS Conference (AIDS 2020). 

Paul Benson, D.O., CUSTOMIZE Investigator and Director of the Be Well Medical Center, said: “Long-acting treatments have the potential to transform how we approach HIV management by replacing daily pills with monthly dosing and require a fresh look at how they can be implemented in our clinics. It’s exciting to see initial findings from CUSTOMIZE showing that a high number of healthcare providers were able to work through the challenges faced in their ‘real-world’ settings and that there is acceptance of the implementation of the once-monthly regimen of cabotegravir and rilpivirine for people living with HIV, by those that participated in the study.”

In the study, 24 healthcare providers and clinic administrators from eight participating sites were surveyed on the acceptability, appropriateness, and feasibility, as well as perceived facilitators and barriers, to implementing the investigational once-monthly, injectable regimen of cabotegravir and rilpivirine. Healthcare provider and clinic administrator perspectives were positive overall, with a large proportion (>84%) indicating they “agreed” or “completely agreed” with the acceptability, appropriateness, and feasibility of implementing the long-acting regimen at the beginning of the study and after four months of implementation. At the study start and month four, acceptability (91.4% and 91.6%), appropriateness (99.1% and 94.8%), and feasibility (90.4% and 84.4%) were relatively consistent and remained high overall. 

The proportion of clinic staff who perceived any barriers to the implementation of the long-acting regimen substantially decreased between the start of the study and the fourth month of the study. At the study start, the top three barriers perceived by clinic staff were the patient’s ability to keep monthly appointments (80.8%), patient access to transportation to and from monthly appointments (76.9%), and the timely ability of clinic staff to make patients aware of missed injection visits (73.1%). After four months of implementation, all perceived barriers saw a substantial decrease among clinic staff (decreased to 37.5%, 37.5%, and 45.8%, respectively). 

Clinical staff were also surveyed on the characteristics of people living with HIV that they felt would be most appropriate for the investigational long-acting regimen of cabotegravir and rilpivirine. According to the healthcare providers and clinic administrators surveyed, individuals for whom long-acting cabotegravir and rilpivirine would be most appropriate included patients who were “tired of taking pills” (88.5%), patients who “have concerns about disclosure of their HIV status” (80.8%) and patients who “experience stress or anxiety over daily adherence with their oral medications” (80.8%). 

Harmony P. Garges, M.D., MPH, Chief Medical Officer at ViiV Healthcare, said: “Challenges can emerge when an investigational treatment moves from the controlled setting of a clinical trial to the real-world setting. The difficulty that patients sometimes face getting access to transportation and keeping monthly appointments were front of mind for the healthcare providers who were part of CUSTOMIZE, but they ultimately found these perceived barriers weren’t as significant as they thought. Exploring innovative solutions to these real-world challenges is precisely why ViiV Healthcare is a leader in the field of implementation science, which aims to identify what works best in healthcare settings, why it works, and how these findings can be applied to improve the lives of people living with HIV.”

The CUSTOMIZE study is ongoing. In addition to these initial four-month healthcare staff survey findings, the full 12-month results, as well as perspectives from healthcare team interviews, and patient experiences with the long-acting regimen will be presented at an upcoming medical meeting. The corresponding CARISEL study, which will examine the implementation of the long-acting regimen of cabotegravir and rilpivirine in European healthcare settings is planned to start later this year.

The long-acting regimen of cabotegravir and rilpivirine was approved by Health Canada in March 2020 and is currently under review by the European Medicines Agency (EMA) and other global regulatory authorities. 

CAB/RPV request for proposals update

As part of its continuing efforts to ensure facilities are prepared to introduce monthly injectable HIV treatment, ViiV Healthcare invited research proposals for Investigator Sponsored Studies (ISSs) in the area of implementation science designed to better understand how to effectively deliver monthly injectable HIV treatment in the real-world setting. A total of six proposals were chosen to further research into the implementation of investigational long-acting cabotegravir and rilpivirine. These studies will explore the implementation of the long-acting regimen in non-HIV clinic settings (including administration in pharmacies or in-home by visiting healthcare workers) as well as addressing challenges of delivery amongst high risk populations (including alternative models of care in community-based organizations or among transgender women in public health settings). 

About CUSTOMIZE (NCT04001803)

CUSTOMIZE is a single-arm, multicenter, one-year evaluation of the effect of an implementation strategy on the degree of acceptability, appropriateness, feasibility, fidelity and sustainability of clinic practices to deliver the investigational once-monthly, injectable regimen of cabotegravir and rilpivirine to appropriate patients living with HIV. The study evaluates both qualitative and quantitative measures across a range of clinic types, including university hospitals as well as private and public clinics, with varied geographic and demographic representation. 

A suite of educational items, training aids, treatment and resource planning tools, appointment reminders and patient-directed support items were made available as part of this study. Staff study participants from each site (physician/primary care practitioner, nurse/medication administration personnel, administrator/clinic manager) took part in the study through participation in surveys and interviews. Sustainment of implementation strategies was assessed via surveys and semi-structured interviews of staff study participants as well as patient study participants. The primary endpoint was change from baseline to the injection site visit at Month 12 in site survey responses for acceptability, appropriateness and feasibility.

For further information please see https://www.clinicaltrials.gov/ct2/show/NCT04001803 

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.

CABENUVA (cabotegravir and rilpivirine extended release injectable suspensions) is currently only approved in Canada. 

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.