ViiV Healthcare announces new collaboration with Janssen to investigate single-tablet regimen for maintenance treatment of HIV-1

- Agreement is ViiV Healthcare's first external collaboration for development of a two drug single-tablet combining dolutegravir and rilpivirine

LONDON, June 12, 2014 /PRNewswire/ -- ViiV Healthcare today announced that they have entered into an agreement with Janssen R&D Ireland Ltd (Janssen) for the development and commercialisation of a single-tablet combining dolutegravir (Tivicay®) and Janssen's non-nucleoside reverse transcriptase inhibitor rilpivirine (Edurant®^[1]). This represents ViiV Healthcare's first external collaboration to develop a single-tablet regimen with another company's branded product and builds on ViiV Healthcare's strategy to expand its portfolio of dolutegravir-based regimens, which started with the approval of dolutegravir for use in combination with other anti-retroviral medicinal products for the treatment of human immunodeficiency virus (HIV-1) infection in adults and children aged 12 years and older weighing at least 40 kg (approx. 88 lbs) in the US, and HIV infected adults and adolescents above 12 years of age in Europe.

As part of this agreement, the two companies will investigate the potential of combining dolutegravir and rilpivirine into a single-tablet in order to expand the treatment options available to people living with HIV. Studies included in the new development programme are expected to begin by Q1 2015 and will investigate the two drug combination regimen as an HIV maintenance therapy for patients already virally suppressed on a three drug regimen. The companies will further investigate the development of paediatric fixed-dose formulations which combine dolutegravir and rilpivirine.

"New options that advance current therapies are increasingly important as patients and clinicians consider HIV care over the long term," said Dr John Pottage, Chief Medical Officer, ViiV Healthcare. "Through this collaboration with Janssen we aim to develop a new combination therapy that meets the needs of patients, and adds to our scientific understanding of dolutegravir."

If approved by regulatory authorities, the two drug fixed-dose combination therapy being developed by ViiV Healthcare and Janssen could offer people living with HIV an option to switch from a standard three drug therapy to a two drug nucleoside reverse transcriptase inhibitors (NRTI)-sparing combination, once a stable suppressed viral load has been achieved.

"ViiV Healthcare's foundation was a novel business model, established to focus on pursuing the most effective outcomes for all people living with HIV. This collaboration builds on our mission to continually develop innovative new solutions to provide people living with HIV new treatment options," said Dr. Dominique Limet, Chief Executive Officer, ViiV Healthcare.

Paediatric licence: The companies will further investigate the development of paediatric fixed-dose combinations of dolutegravir and rilpivirine. There are about 3.3 million children living with HIV worldwide; approximately 66% of those needing treatment do not have access to appropriate care and medicines. Among several barriers preventing further scale up of the numbers of children on treatment is the lack of medicines that are palatable and acceptable for use by children^[i].

Since the company's founding, ViiV Healthcare has been committed to improving scientific understanding and treatment options for infants and children living with HIV. This includes a broad range of initiatives supported through a £10 million Paediatric Innovation Seed Fund, which aims to improve paediatric HIV research, care and treatment in resource-limited settings, and the Positive Action for Children Fund which supports 150 organisations across 30 countries to deliver programmes designed to prevent mother-to-child transmission of HIV.

Important Information about Tivicay® (dolutegravir)
FDA Indication and Usage in the US: 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 children aged 12 years and older and weighing at least 40 kg. The following should be considered prior to initiating TIVICAY: poor virologic response was observed in subjects treated with TIVICAY 50 mg twice daily with an INSTI-resistance Q148 substitution plus 2 or more additional INSTI-resistance substitutions including L74I/M, E138A/D/K/T, G140A/S, Y143H/R, E157Q, G163E/K/Q/R/S, or G193E/R.

Important Safety Information for Tivicay® (dolutegravir)
Contraindication: Co-administration of TIVICAY with dofetilide (anti-arrhythmic) is contraindicated due to the potential for increased dofetilide plasma concentrations and the risk for serious and/or life-threatening events.

Hypersensitivity Reactions: Hypersensitivity reactions have been reported and were characterised by rash, constitutional findings, and sometimes organ dysfunction, including liver injury. The events were reported in 1% or fewer subjects receiving TIVICAY in Phase 3 clinical trials. Immediately discontinue TIVICAY and other suspect agents if signs or symptoms of hypersensitivity reaction develop, (including but not limited to, severe rash or rash accompanied by fever, general malaise, fatigue, muscle or joint aches, blisters or peeling of the skin, oral blisters or lesions, conjunctivitis, facial edema, hepatitis, eosinophilia, angioedema, difficulty breathing.) Monitor clinical status, including liver aminotransferases, and initiate appropriate therapy. Delay in stopping treatment with TIVICAY or other suspect agents after the onset of hypersensitivity may result in a life-threatening reaction. TIVICAY should not be used in patients who have experienced a hypersensitivity reaction to TIVICAY.

Effects on Serum Liver Biochemistries in Patients with Hepatitis B or C Coinfection: Patients with underlying hepatitis B or C may be at increased risk for worsening or development of transaminase elevations with use of TIVICAY. 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. Appropriate laboratory testing prior to initiating therapy and monitoring for hepatotoxicity during therapy with TIVICAY are recommended in patients with underlying hepatic disease such as hepatitis B or C.

Fat Redistribution: Redistribution/accumulation of body fat has been observed in patients receiving antiretroviral therapy.

Immune Reconstitution Syndrome: During the initial phase of treatment, immune reconstitution syndrome can occur, which may necessitate further evaluation and treatment. Autoimmune disorders have been reported to occur in the setting of immune reconstitution; the time to onset is more variable and can occur many months after initiation of treatment.

Adverse Reactions: The most commonly reported (≥2%) adverse reactions of moderate to severe intensity in treatment naïve adult subjects in any one trial receiving TIVICAY in a combination regimen were insomnia (3%) and headache (2%).

Drug Interactions: Co-administration of TIVICAY with drugs that are strong inducers of UGT1A1 and/or CYP3A4 may result in reduced plasma concentrations of dolutegravir and require dose adjustments of TIVICAY.
- TIVICAY should be taken 2 hours before or 6 hours after taking cation-containing antacids or laxatives, sucralfate, oral iron supplements, oral calcium supplements, or buffered medications.
- Consult the full Prescribing Information for TIVICAY for more information on potentially significant drug interactions, including clinical comments.

Pregnancy: Pregnancy category B. TIVICAY should be used during pregnancy only if the potential benefit justifies the potential risk. An Antiretroviral Pregnancy Registry has been established.

Breastfeeding: Breastfeeding is NOT recommended due to the potential for HIV transmission and the potential for adverse reactions in nursing infants.

Paediatric Patients: Safety and efficacy of TIVICAY has not been established in children younger than 12 years old, or weighing <40 kg, or in INSTI-experienced paediatric patients with documented or clinically suspected INSTI resistance.

Please visit the following link for the full US prescribing and patient information: https://www.viivhealthcare.com/media/58599/us_tivicay.pdf.

About Tivicay Mode of Action
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. It is available as a small, yellow, 50 mg tablet. Importantly, it can be taken with or without food and at any time of the day.

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. Shionogi joined as a 10% 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 new HIV medicines, 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.

Important Safety Information for Edurant® (rilpivirine)

Can EDURANT® be taken with other medicines?

EDURANT® may affect the way other medicines work and other medicines may affect how EDURANT® works and may cause serious side effects. If you take certain medicines with EDURANT®, the amount of EDURANT® in your body may be too low and it may not work to help control your HIV infection, and the HIV virus in your body may become resistant to EDURANT® or other HIV medicines that are like it. To help get the right amount of medicine in your body, you should always take EDURANT® with a meal. A protein drink alone does not replace a meal.

Do not take EDURANT® if:

• Your HIV infection has been previously treated with HIV medicines
• You are taking any of the following medicines:
  • Anti-seizure medicines: carbamazepine (Carbatrol®, Equetro®, Tegretol®, Tegretol-XR®, Teril®, Epitol®), oxcarbazepine (Trileptal®), phenobarbital (Luminal®), phenytoin (Dilantin®, Dilantin-125®, Phenytek®)
  • Anti-tuberculosis (anti-TB) medicines: rifampin (Rifater®, Rifamate®, Rimactane®, Rifadin®), rifapentine (Priftin®)
  • Proton pump inhibitor (PPI) medicine for certain stomach or intestinal problems: esomeprazole (Nexium®, Vimovo®), lansoprazole (Prevacid®), omeprazole (Prilosec®, Zegerid®), pantoprazole sodium (Protonix®), rabeprazole (Aciphex®)
  • More than 1 dose of the steroid medicine dexamethasone or dexamethasone sodium phosphate
  • St. John's wort (Hypericum perforatum)

Especially tell your doctor if you take:

• Rifabutin (Mycobutin®, a medicine to treat some bacterial infections). Talk to your doctor or pharmacist about the right amount of EDURANT you should take if you also take rifabutin.
• Medicines used to treat HIV
• An antacid medicine that contains aluminum, magnesium hydroxide, or calcium carbonate. Take antacids at least 2 hours before or at least 4 hours after you take EDURANT®
• Medicines to block acid in your stomach, including cimetidine (Tagamet®), famotidine (Pepcid®), nizatidine (Axid®), or ranitidine hydrochloride (Zantac®). Take these medicines at least 12 hours before or at least 4 hours after you take EDURANT®
• Any of these medicines (if taken by mouth or injection): clarithromycin (Biaxin®), erythromycin (E-Mycin®, Eryc®, Ery-Tab®, PCE®, Pediazole®, Ilosone®), fluconazole (Diflucan®), itraconazole (Sporanox®), ketoconazole (Nizoral®), methadone (Dolophine®), posaconazole (Noxafil®), telithromycin (Ketek®), voriconazole (Vfend®)

This is not a complete list of medicines. Before starting EDURANT®, be sure to tell your healthcare professional about all the medicines you are taking or plan to take, including prescription and nonprescription medicines, vitamins, and herbal supplements.

Before taking EDURANT®, also tell your healthcare professional if you have had or currently have liver problems (including hepatitis B or C), have ever had a mental health problem, are pregnant or planning to become pregnant, or breastfeeding. It is not known if EDURANT® will harm your unborn baby. You and your healthcare professional will need to decide if taking EDURANT® is right for you.

• Do not breastfeed if you are taking EDURANT®. You should not breastfeed if you have HIV because of the chance of passing HIV to your baby

What are the possible side effects of EDURANT®?

EDURANT® can cause serious side effects including:

• Depression or mood changes. Tell your doctor 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
• Liver problems. 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. Liver problems were also reported during treatment in some people without a history of liver disease. Your healthcare professional may need to do tests to check liver function before and during treatment
• Changes in body shape or body fat have been seen in some patients taking HIV medicines. The exact cause and long-term health effects of these conditions are not known
• Changes in your immune system (immune reconstitution syndrome). Your immune system may get stronger and begin to fight infections. Tell your healthcare professional right away if you start having any new symptoms of infection.

Other 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 professional right away. Do not stop taking EDURANT® or any other medications without first talking to your healthcare professional.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch, or call 1-800-FDA-1088.

Please see full Product Information for more details: http://www.edurant.com/sites/default/files/EDURANT-PI.pdf

About Edurant® (rilpivirine)

Rilpivirine was developed by Janssen R&D Ireland Ltd, one of the Janssen Pharmaceutical Companies. Rilpivirine is a tablet dosed at 25mg taken once a day in combination with other antiviral. The overall safety profile of rilpivirine is based on Phase III clinical studies. In the rilpivirine arm, the most frequently reported adverse drug reactions (≥ 2%) that were at least of moderate intensity were depression (3.5%), insomnia (2.9%), headache (2.6%) and rash (2.2%).

Rilpivirine is available in the United States (US) and the European Union as part of a once daily fixed dose antiretroviral combination with Gilead Sciences Inc's tenofovir and emtricitabine. This combination, known as COMPLERA® (US) or EVIPLERA®, was granted marketing authorisation from the Food and Drug Administration in August 2011, with Gilead Sciences Inc being the marketing authorisation holder in the US, and from the European Commission in November 2011, with Gilead Sciences International Ltd. being the marketing authorisation holder in Europe, Middle East and Africa.