ViiV Healthcare Shares Data from Landmark 2-Drug Regimen Trials At AIDS 2018

John C Pottage, Jr, MD, Chief Scientific and Medical Officer, ViiV Healthcare, commented, “As we see advancements in the treatment options available to people living with HIV, our research efforts over the past few years have been focused on moving beyond viral load and addressing some of the unresolved issues that people living with HIV face, such as the potential long-term risks and toxicities that can be associated with lifelong antiretroviral therapy. We look forward to sharing the primary endpoint 48-week data from the GEMINI 1 & 2 studies, that investigates a 2-drug regimen in treatment-naïve patients against a standard three-drug regimen; as well as 100-week data from the SWORD 1 & 2 studies for virologically-suppressed patients. AIDS 2018 will be an important moment in our innovative 2-drug regimen research and development programme, with results that affirm our 2-drug regimen strategy, and reinforce our belief that many patients can control their disease with two drugs instead of three or more.”

Data from a 2-drug regimen of dolutegravir and lamivudine in treatment-naïve patients

The GEMINI 1 & 2 phase III studies compare a 2-drug regimen of dolutegravir plus lamivudine to a three-drug regimen of dolutegravir plus the fixed-dose tablet tenofovir/emtricitabine. Primary endpoint results at 48-weeks showing efficacy of a dolutegravir and lamivudine 2-drug regimen compared to the three-drug regimen in treatment-naïve people living with HIV (PLHIV) will be presented.

100-week data from the 2-drug regimen of dolutegravir and rilpivirine (Juluca) in virologically-suppressed patients

The SWORD 1 & 2 phase III studies evaluated the safety and efficacy of switching virologically-suppressed PLHIV from a three- or four-drug antiretroviral regimen to a 2-drug regimen of dolutegravir and rilpivirine. The 148-week data will be shared in 2019.

Patient reported outcomes data for an investigational long-acting injectable regimen of cabotegravir and rilpivirine in virologically-suppressed patients

LATTE-2 is a phase IIb, open-label study investigating the 2-drug regimen of cabotegravir and rilpivirine, each in a long-acting, injectable formulation, for patients with HIV-1 infection who had already achieved viral suppression with a three-drug oral regimen of cabotegravir plus two nucleoside reverse transcriptase inhibitors. Data on adherence and satisfaction, tolerability and acceptability will be presented, supporting the goal of providing a long-acting regimen to PLHIV as an alternative to daily oral pills.

Key insights from partners of PLHIV

The international Positive Perspectives survey explores the impact an HIV diagnosis has on the quality of life, outlook and aspirations of PLHIV, and their partners. An analysis of responses from the partners of PLHIV will be presented at AIDS 2018.

The full list of data presented by ViiV Healthcare at AIDS 2018 is listed below:

Dolutegravir

Dolutegravir + lamivudine

Dolutegravir + rilpivirine

Cabotegravir

Fostemsavir

Other/Non-Product Related

Other/Treatment Related

- Ends –

Notes to editors

About HIV

HIV stands for the Human Immunodeficiency Virus. Unlike some other viruses, the human body cannot get rid of HIV, so once someone has HIV they have it for life. There is no cure for HIV, but effective treatment can control the virus so that people with HIV can enjoy healthy and productive lives.

HIV has largely become a chronic treatable disease with improved access to antiretroviral treatment. This has led to a 22% drop in global HIV mortality between 2009 and 2013,¹ but more can be done for the estimated 36.7 million people living with HIV² of which 160,000 were newly diagnosed in the Europe region alone in 2016.³

U.S INDICATIONS AND IMPORTANT SAFETY INFORMATION

About Tivicay^® (dolutegravir)

Dolutegravir (Tivicay) is an integrase strand transfer inhibitor (INSTI) for use in combination with other antiretroviral agents for the treatment of HIV. Integrase inhibitors block 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. Tivicay is approved in over 100 countries across North America, Europe, Asia, Australia, Africa and Latin America.

TIVICAY (dolutegravir) tablets

Professional Indication(s) and Important Safety Information

U.S. Indications and Usage

TIVICAY is a human immunodeficiency virus type 1 (HIV-1) integrase strand transfer inhibitor (INSTI) indicated in combination with:

• other antiretroviral agents for the treatment of HIV-1 infection in adults and pediatric patients weighing at least 30 kg
• rilpivirine as a complete regimen for the treatment of HIV-1 infection in adults to replace the current antiretroviral regimen in those who are virologically suppressed (HIV-1 RNA < 50 copies per mL) on a stable antiretroviral regimen for ≥6 months with no history of treatment failure or known substitutions associated with resistance to either antiretroviral agent.

Important safety information: Tivicay (dolutegravir)

The following ISI is based on the Highlights section of the Prescribing Information for Tivicay. Please consult the full Prescribing Information for all the labelled safety information for Tivicay.

Contraindications

• Previous hypersensitivity reaction to dolutegravir.
• Coadministration with dofetilide.

Warnings and precautions

• Hypersensitivity reactions characterized by rash, constitutional findings, and sometimes organ dysfunction, including liver injury, have been reported. Discontinue TIVICAY and other suspect agents immediately if signs or symptoms of hypersensitivity reactions develop, as a delay in stopping treatment may result in a life-threatening reaction.
• Hepatotoxicity has been reported in patients receiving dolutegravir-containing regimens. Patients with underlying hepatitis B or C may be at increased risk for worsening or development of transaminase elevations. Monitoring for hepatoxicity is recommended.
• Immune reconstitution syndrome has been reported in patients treated with combination antiretroviral therapy.

Adverse reactions

The most common adverse reactions of moderate to severe intensity and incidence at least 2% (in those receiving TIVICAY in any one adult trial) are insomnia, fatigue, and headache.

Drug interactions

• Refer to the full prescribing information for important drug interactions with TIVICAY.
• Drugs that are metabolic inducers may decrease the plasma concentrations of dolutegravir.
• TIVICAY should be taken 2 hours before or 6 hours after taking cation-containing antacids or laxatives, sucralfate, oral supplements containing iron or calcium, or buffered medications. Alternatively, TIVICAY and supplements containing calcium or iron can be taken together with food.

Use in specific populations

• Pregnancy: TIVICAY should be used during pregnancy only if the potential benefit justifies the potential risk.
• Lactation: Breastfeeding is not recommended.

Full US prescribing information including is available at:

https://www.gsksource.com/pharma/content/dam/GlaxoSmithKline/US/en/Prescribing_Information/Tivicay/pdf/TIVICAY-PI-PIL.PDF

For the EU Summary of Product Characteristics, please visit:

https://www.medicines.org.uk/emc/medicine/28545

About Epivir^® (lamivudine)

Lamivudine is a nucleoside analogue used in combination with other antiretroviral agents for the treatment of HIV infection. Lamivudine is available in branded (Epivir) and generic forms. Trademarks are owned by or licensed to the ViiV Healthcare group of companies.

EPIVIR 300mg TABLETS

Professional Indication(s) and Important Safety Information

U.S. Indications and Usage

EPIVIR is a nucleoside analogue reverse transcriptase inhibitor indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection.

Limitations of Use: The dosage of this product is for HIV-1 and not HBV.

Important safety information (ISI): Epivir (lamivudine) tablets

The following ISI is based on the Highlights section of the Prescribing Information for Epivir. Please consult the full Prescribing Information for all the labelled safety information for Epivir.

Warning: Exacerbations of Hepatitis B, and different formulations of Epivir

See full prescribing information for complete boxed warning.

• Severe acute exacerbations of hepatitis B have been reported in patients who are co-infected with hepatitis B virus (HBV) and human immunodeficiency virus (HIV-1) and have discontinued EPIVIR. Monitor hepatic function closely in these patients and, if appropriate, initiate anti-hepatitis B treatment.
• Patients with HIV-1 infection should receive only dosage forms of EPIVIR appropriate for treatment of HIV-1.

Contraindications

• EPIVIR is contraindicated in patients with previous hypersensitivity reaction to lamivudine.

Warnings and precautions

• Co-infected HIV-1/HBV Patients: Emergence of lamivudine-resistant HBV variants associated with lamivudine-containing antiretroviral regimens has been reported.
• Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogues.
• Hepatic decompensation, some fatal, has occurred in HIV-1/HCV co-infected patients receiving interferon and ribavirin-based regimens. Monitor for treatment-associated toxicities. Discontinue EPIVIR as medically appropriate and consider dose reduction or discontinuation of interferon alfa, ribavirin, or both.
• Pancreatitis: Use with caution in pediatric patients with a history of pancreatitis or other significant risk factors for pancreatitis. Discontinue treatment as clinically appropriate. (5.4)
• Immune reconstitution syndrome has been reported in patients treated with combination antiretroviral therapy.
• Lower virologic suppression rates and increased risk of viral resistance were observed in pediatric subjects who received EPIVIR oral solution concomitantly with other antiretroviral oral solutions compared with those who received tablets. An all-tablet regimen should be used when possible.

Adverse reactions

• The most common reported adverse reactions (incidence greater than or equal to 15%) in adults were headache, nausea, malaise and fatigue, nasal signs and symptoms, diarrhea, and cough.
• The most common reported adverse reactions (incidence greater than or equal to 15%) in pediatric subjects were fever and cough.

Drug interactions

• Sorbitol: Coadministration of lamivudine and sorbitol may decrease lamivudine concentrations; when possible, avoid chronic coadministration.

Use in specific populations

• Lactation: Women infected with HIV should be instructed not to breastfeed due to potential for HIV transmission.

Full US prescribing information including is available at:

https://www.gsksource.com/pharma/content/dam/GlaxoSmithKline/US/en/Prescribing_Information/Epivir/pdf/EPIVIR-PI-PIL.PDF

For the EU Summary of Product Characteristics, please visit:

https://www.medicines.org.uk/emc/product/943

About Juluca^® (dolutegravir/rilpivirine)

Juluca is ViiV Healthcare’s first two-drug regimen (2DR), once-daily, single-pill that combines dolutegravir 50mg (ViiV Healthcare), the most widely prescribed integrase inhibitor (INI) worldwide, with the nucleoside reverse transcriptase inhibitor (NNRTI) rilpivirine 25mg (Janssen Sciences Ireland UC). Juluca was granted marketing authorisation by regulatory authorities in the United States in November 2017, the European Union and Canada in May 2018, and Australia in June 2018. ^4,5,6,7 ViiV Healthcare has also submitted regulatory marketing applications in other countries worldwide.

Juluca is indicated for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in adults who are virologically-suppressed (HIV-1 RNA < 50 copies/mL) on a stable antiretroviral regimen for at least six months with no history of virological failure and no known or suspected resistance to any NNRTI or INI.⁴

U.S. IMPORTANT SAFETY INFORMATION: JULUCA (dolutegravir and rilpivirine) tablets

Professional Indication(s) and Important Safety Information

Indication and Usage for JULUCA

JULUCA 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 those who are virologically suppressed (HIV-1 RNA <50 copies/mL) on a stable antiretroviral regimen for ≥6 months with no history of treatment failure and no known substitutions associated with resistance to the individual components of JULUCA.

Important Safety Information

CONTRAINDICATIONS

JULUCA is contraindicated in patients:

• with previous hypersensitivity reaction to dolutegravir or rilpivirine.
• receiving dofetilide, carbamazepine, oxcarbazepine, phenobarbital, phenytoin, rifampin, rifapentine, systemic dexamethasone (>1 dose), St. John’s wort, and proton pump inhibitors (e.g., esomeprazole, lansoprazole, omeprazole, pantoprazole, and rabeprazole).

WARNINGS AND PRECAUTIONS

Skin and Hypersensitivity Reactions:

• Hypersensitivity reactions have been reported with dolutegravir and were characterized by rash, constitutional findings, and sometimes organ dysfunction, including liver injury. These events were reported in <1% of subjects receiving dolutegravir in Phase 3 clinical trials.
• Severe skin and hypersensitivity reactions have been reported during postmarketing experience, including cases of Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), with rilpivirine-containing regimens and have been accompanied by fever and/or organ dysfunctions including elevations in hepatic serum biochemistries.
• Discontinue JULUCA immediately if signs or symptoms of severe skin or hypersensitivity reactions develop (such as severe rash or rash accompanied by fever, general malaise, fatigue, muscle or joint aches, blisters or peeling of the skin, mucosal involvement, conjunctivitis, facial edema, hepatitis, eosinophilia, angioedema, and difficulty breathing), as a delay in stopping treatment may result in a life-threatening reaction. Clinical status, including laboratory parameters with liver aminotransferases, should be monitored and appropriate therapy initiated.

Hepatotoxicity:

• Hepatic adverse events have been reported, including cases of hepatic toxicity, in patients without pre-existing hepatic disease or other identifiable risk factors.
• Patients with underlying hepatitis B or C or marked elevations in transaminases prior to treatment may be at increased risk for worsening or development of transaminase elevations. In some cases, the elevations in transaminases were consistent with immune reconstitution syndrome or hepatitis B reactivation, particularly in the setting where anti-hepatitis therapy was withdrawn.
• Monitoring for hepatotoxicity is recommended.

Depressive Disorders:

• Depressive disorders (including depressed mood, depression, dysphoria, major depression, mood altered, negative thoughts, suicide attempt, and suicidal ideation) have been reported.
• Promptly evaluate patients with severe depressive symptoms.

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

• The concomitant use of JULUCA and other drugs may result in known or potentially significant drug interactions, see Contraindications and Drug Interactions sections. Rilpivirine doses 3 and 12 times higher than the recommended dose can prolong the QTc interval. Consider alternatives to JULUCA when coadministered with a drug with a known risk of Torsade de Pointes. Consider the potential for drug interactions prior to and during therapy with JULUCA and monitor for adverse reactions.

ADVERSE REACTIONS: Most common adverse reactions with JULUCA (incidence ≥2%, all Grades) were diarrhea (2%) and headache (2%).

DRUG INTERACTIONS

• Because JULUCA is a complete regimen, coadministration with other antiretroviral medications for the treatment of HIV-1 infection is not recommended.
• Drugs that induce or inhibit CYP3A or UGT1A1 may affect the plasma concentrations of the components of JULUCA.
• Drugs that increase gastric pH or containing polyvalent cations may decrease plasma concentrations of the components of JULUCA.
• Consider alternatives to prescribing JULUCA with drugs with a known risk of Torsade de Pointes.
• Consult the full Prescribing Information for JULUCA for more information on potentially significant drug interactions, including clinical comments.

USE IN SPECIFIC POPULATIONS

• Pregnancy: There are insufficient prospective pregnancy data to adequately assess the risk of birth defects and miscarriage. An Antiretroviral Pregnancy Registry has been established.
• Lactation: Breastfeeding is not recommended due to the potential for HIV-1 transmission and the potential for adverse reactions in nursing infants.

DOSAGE AND ADMINISTRATION

• Dosage: 1 tablet taken orally once daily with a meal for adult patients.
• Recommended Dosage of JULUCA with Rifabutin Coadministration: Take an additional 25-mg tablet of rilpivirine with JULUCA once daily with a meal for the duration of the rifabutin coadministration.

Full US prescribing information including is available at:

https://www.gsksource.com/pharma/content/dam/GlaxoSmithKline/US/en/Prescribing_Information/Juluca/pdf/JULUCA-PI-PIL.PDF

For the EU Summary of Product Characteristics, please visit:

https://www.medicines.org.uk/emc/product/9246

About cabotegravir

Cabotegravir is an investigational integrase strand transfer inhibitor (INSTI) 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 and is currently being evaluated as a long-acting formulation for intramuscular injection (with a once-daily oral tablet being used to establish safety and tolerability in individuals prior to long-acting injection).

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)

Please read Important Safety Information below, and talk to your healthcare provider to learn if EDURANT^® is right for you.

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
• pantoprazole sodium
• 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:

• 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 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:

http://www.janssenlabels.com/package-insert/product-monograph/prescribing-information/EDURANT-pi.pdf

For the EU Summary of Product Characteristics, please visit:

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

Tivicay, Epivir and Juluca are trademarks owned by the ViiV Healthcare group of companies.

Edurant is a registered trademark of Janssen Sciences Ireland UC.

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 – one of the world’s leading research-based pharmaceutical and healthcare companies – is committed to improving the quality of human life by enabling people to do more, feel better and live longer. For further information please visit www.gsk.com.

References

¹ World Health Organization. Global Update on the health sector response to HIV, 2014. July 2014. Available at: http://apps.who.int/iris/bitstream/10665/128494/1/9789241507585_eng.pdf?ua=1 Last accessed May 2018.

² World Health Organization. HIV AIDS Factsheet 2017. Available at: http://www.who.int/mediacentre/factsheets/fs360/en/ Last accessed July 2018.

³ World Health Organization. Infographic - Newly diagnosed HIV infections in the WHO European Region, 2016. Available at: http://www.euro.who.int/en/health-topics/communicable-diseases/hivaids/data-and-statistics/infographic-newly-diagnosed-hiv-infections-in-the-who-european-region,-2016 Last accessed July 2018.

⁴ Juluca EU Summary of Product Characteristics www.ema.europa.eu.

⁵ Juluca (dolutegravir and rilpivirine) Prescribing Information. U.S Approval 2017.

⁶ Health Canada. Juluca certified product information document. 18 May 2018.

⁷ Australian Government. Department of Health Therapeutic Goods Administration. Juluca Product Information - ARTG ID 291356. Available at: https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2018-PI-01956-1&d=2018062916114622483 Last accessed July 2018.

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