ViiV Healthcare announces start of first-ever study to identify and evaluate approaches to implementing its once-monthly injectable HIV treatment in clinical practice

The long-acting injectable regimen has been granted Priority Review status by the FDA, with a target approval date set for December 29, 2019

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 CUSTOMIZE trial (Cabotegravir plus Rilpivirine in the US To Optimize and Measure Implementation and Experience), which aims to identify and evaluate approaches to implementing a once-monthly, injectable treatment for HIV into clinical practice.

A team from ViiV Healthcare will work with clinical staff at diverse practice sites across the US 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 a monthly injectable treatment regimen if approved, including how to address the increased frequency of clinic visits.

Richard Elion, M.D., Director of Clinical Research at the Washington Health Institute, said: “With daily oral antiretroviral therapies, physicians see their patients once or twice per year. If approved, the injectable regimen of cabotegravir and rilpivirine would require people living with HIV to receive injections from a healthcare provider every month. Although some people living with HIV may prefer once monthly visits to their provider, this would be a paradigm shift in the treatment of HIV, and providers may encounter challenges delivering a smooth service. The CUSTOMIZE trial will help to generate data that enable medical practices to be well prepared for incorporating this novel approach into the clinic setting.”

In April 2019, ViiV Healthcare submitted a New Drug Application (NDA) to the US Food and Drug Administration (FDA) for the two-drug regimen of cabotegravir (ViiV Healthcare) and rilpivirine (Janssen) to treat HIV-1 infection in adults whose viral load is suppressed and who are not resistant to cabotegravir or rilpivirine. If approved, the regimen would be the first-ever long-acting, injectable therapy for the treatment of HIV. In June, the FDA granted the NDA Priority Review, a designation for drugs considered significant improvements in the treatment, diagnosis, or prevention of a serious disease. A Priority Review designation means the FDA’s goal is to take action on an application within six months (compared to ten months under standard review). The FDA has set a target approval date of December 29, 2019.

The CUSTOMIZE trial is currently enrolling patients in medical clinics in nine US cities that were chosen to create a representative sample of clinic types, including university hospitals, private and public clinics in rural, suburban and urban areas: Sacramento, Dallas, Kansas City, Jackson, Detroit, Washington DC, Atlanta, Jacksonville and Miami.

Participating medical facilities will receive educational items, training aids, treatment and resource planning tools, appointment reminders and patient-facing materials at the beginning of the study. The sites will determine if or how they will use these materials and may also create their own clinic-developed resources. ViiV Healthcare will facilitate surveys and interviews throughout the trial with the physicians, nurses, administrators and patients, to share best practices and help identify barriers and facilitators to the successful delivery of monthly injectable HIV treatment. Initial results are anticipated by the end of the year.

Harmony P. Garges, M.D., MPH, Head of Global Medical Affairs at ViiV Healthcare, said: “With the CUSTOMIZE study, ViiV Healthcare is aiming to identify and evaluate different approaches to implementing a monthly injectable HIV treatment in the real world, which can be different from the controlled setting of a clinical trial. Experts believe effective implementation of HIV treatment could have the greatest contribution towards ending the HIV epidemic and we believe this study is an important step towards that goal.”

Implementation Science program is launching “call for proposals” to identify innovative research projects to optimize cabotegravir and rilpivirine health service delivery in the US
As part of its efforts to ensure facilities are prepared to introduce monthly injectable HIV treatment, ViiV Healthcare is also inviting 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. Beginning August 2019, an online submission form to submit a letter of intent will be made available through www.hivimplementationscience.com. The submission deadline for the letter of intent is November 1, 2019 and final proposals are due November 15, 2019.

About CUSTOMIZE

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 once-monthly, injectable regimen of cabotegravir and rilpivirine to appropriate patients living with HIV. The study will evaluate 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 will be made available as part of this study. These items and tools will be directed toward HCPs as well as patients and will comprise the study toolkit. Staff study participants from each site (physician/PCP, nurse/medication administration personnel, administrator/clinic manager) will take part in this study, including participation in surveys and interviews. Sustainment of implementation strategies will be assessed via surveys and semi-structured interviews of staff study participants as well as patient study participants. The primary endpoint is change from baseline to the injection site visit at Month 12 in site survey responses for acceptability, appropriateness and feasibility.

About cabotegravir

Cabotegravir is an investigational integrase inhibitor (INI) and is not approved by regulatory authorities anywhere in the world. Cabotegravir is being developed by ViiV Healthcare for the treatment and prevention of HIV. It is being evaluated as a long-acting formulation for intramuscular injection and also as a once-daily oral tablet for use as a lead-in, to establish the tolerability of cabotegravir prior to long- acting injection.

About rilpivirine

EDURANT® (rilpivirine) is a once daily non-nucleoside reverse transcriptase inhibitor (NNRTI) used for the treatment of human immunodeficiency virus (HIV-1) infection in combination with other antiretroviral

agents in antiretroviral treatment-naïve patients 12 years of age and older and weighing at least 35-kg with a viral load ≤ 100,000 HIV RNA copies/mL. Long-acting injectable rilpivirine is not approved by regulatory authorities anywhere in the world.

Rilpivirine was developed by Janssen Sciences Ireland UC, one of the Janssen Pharmaceutical Companies of Johnson & Johnson. Rilpivirine is approved in the US and EU as EDURANT® as a 25mg tablet taken once- a-day and is always taken with a meal. The most common side effects of EDURANT include: depression, headache, trouble sleeping (insomnia) and rash.

Important Safety Information (ISI) for EDURANT® (Rilpivirine)

Note: this is taken from the US label and local variations apply. Please refer to applicable local labelling.

About EDURANT® (Rilpivirine)

  • EDURANT® (rilpivirine) is a prescription medicine that is used with other antiretroviral medicines to treat Human Immunodeficiency Virus-1 (HIV-1) in people 12 years of age and older and who weigh at least 77 lbs (35 kg):
    • Have never taken HIV medicines before, and
    • Have an amount of HIV in their blood (called “viral load”) that is no more than 100,000 copies/mL
  • EDURANT® is not recommended for patients less than 12 years of age or who weigh less than 77 lbs (35 kg)

IMPORTANT SAFETY INFORMATION

Who should not take EDURANT®?
Do not take EDURANT® if you also take:

  • anti-seizure medicines:
    • carbamazepine
    • oxcarbazepine
    • phenobarbital
    • phenytoin
  • anti-tuberculosis (anti-TB) medicines:
    • rifampin
    • rifapentine
  • proton pump inhibitor (PPI) medicine for certain stomach or intestinal problems:
    • esomeprazole
    • lansoprazole
    • omeprazole
    • pantoprazolesodium
    • rabeprazole
  • more than 1 dose of the steroid medicine dexamethasone or dexamethasone sodium phosphate
  • St. John’s wort (Hypericum perforatum)

What should I tell my healthcare provider before taking EDURANT®?
Before taking EDURANT®, tell your healthcare provider about all your medical conditions, including if you:

  • have or had liver problems, including hepatitis B or C virus infection
  • have kidney problems
  • have ever had a mental health problem
  • are pregnant or plan to become pregnant. It is not known if EDURANT® will harm your unborn baby.
    Tell your healthcare provider if you become pregnant during treatment with EDURANT®.
  • are breastfeeding or plan to breastfeed. Do not breastfeed if you take EDURANT®.
    • You should not breastfeed if you have HIV-1 because of the risk of passing HIV-1 to your baby.
    • It is not known if EDURANT® passes into your breast milk. Talk with your healthcare provider about the best way to feed your baby during EDURANT® treatment.

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.
Do not start taking a new medicine without telling your healthcare provider. Your healthcare provider can tell you if it is safe to take EDURANT® with other medicines.

How should I take EDURANT®?

  • Take EDURANT® every day exactly as your healthcare provider tells you to.
  • Take EDURANT® 1 time each day with a meal. A protein drink alone does not replace a meal.
  • Do not change your dose or stop taking EDURANT® without first talking with your healthcare provider. Stay under the care of your healthcare provider during treatment with EDURANT®.
  • Do not miss a dose of EDURANT®.
  • If you take an H2-receptor antagonist (famotidine, cimetidine, nizatidine, or ranitidine), you should take these medicines at least 12 hours before or at least 4 hours after you take EDURANT®.
  • If you take antacids, or other products that contain aluminum, calcium carbonate, or magnesium hydroxide, you should take these medicines at least 2 hours before or at least 4 hours after you take EDURANT®.
  • If you miss a dose of EDURANT® within 12 hours of the time you usually take it, take your dose of EDURANT® with a meal as soon as possible. Then, take your next dose of EDURANT® at the regularly scheduled time. If you miss a dose of EDURANT® by more than 12 hours of the time you usually take it, wait and then take the next dose of EDURANT® at the regularly scheduled time.
  • Do not take more than your prescribed dose to make up for a missed dose.
  • If you take too much EDURANT®, call your healthcare provider or go to the nearest hospital emergency room right away.

What are the possible side effects of EDURANT®?

EDURANT® can cause serious side effects including:

  • Severe skin rash and allergic reactions. Skin rash is a common side effect of EDURANT®. Skin rash can be serious. Call your healthcare provider right away if you get a rash. In some cases, rash and allergic reaction may need to be treated in a hospital.
  • If you get a rash with any of the following symptoms, stop taking EDURANT® and get medical help right away:
    • fever
    • skin blisters
    • mouth sores
    • redness or swelling of the eyes(conjunctivitis)
    • swelling of the face, lips, mouth, tongue, or throat
    • trouble breathing or swallowing
    • pain on the right side of the stomach (abdominal) area
    • dark-colored urine “tea colored”
  • Change in liver enzymes. People with a history of hepatitis B or C virus infection or who have certain liver function test changes may have an increased risk of developing new or worsening liver problems during treatment with EDURANT®. Liver problems have also happened during treatment with EDURANT® in people without a history of liver disease. Your healthcare provider may need to do tests to check your liver enzymes before and during treatment with EDURANT®.
  • Depression or mood changes. Tell your healthcare provider right away if you have any of the following symptoms:
    • feeling sad or hopeless
    • feeling anxious or restless
    • have thoughts of hurting yourself (suicide) or have tried to hurt yourself
  • Changes in body fat can happen in people who take HIV medicine. These changes may include increased amount of fat in the upper back and neck (“buffalo hump”), breast, and around the middle of your body (trunk). Loss of fat from the legs, arms, and face may also happen. The exact cause and long-term health effects of these problems are not known.
  • Changes in your immune system (Immune Reconstitution Syndrome) can happen when you start taking HIV medicines. Your immune system may get stronger and begin to fight infections that have been hidden in your body for a long time. Tell your healthcare provider right away if you start having any new symptoms after starting your HIV-1 medicine.

The most common side effects of EDURANT® include depression, headache, trouble sleeping (insomnia), and rash.
This is not a complete list of all side effects. If you experience these or other symptoms, contact your healthcare provider right away. Do not stop taking EDURANT® or any other medications without first talking to your healthcare provider.

You are encouraged to report side effects of prescription drugs to the FDA. Visit http://www.fda.gov/medwatch, or call 1-800-FDA-1088. You may also report side effects to Janssen Products, LP, at 1-800-JANSSEN (1-800-526-7736).

Please see accompanying full Product Information for more details.
Full US prescribing information including is available at: www.janssenlabels.com/package-insert/product-monograph/prescribing- information/EDURANT-pi.pdf

For the EU Summary of Product Characteristics, please visit:

www.ema.europa.eu/docs/en_GB/document_library/EPAR_- _Product_Information/human/002264/WC500118874.pdf

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 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.