ViiV Healthcare

ViiV Healthcare Begins Phase III Programme with dolutegravir/rilpivirine Combination for HIV Maintenance Therapy

London (ots/PRNewswire) - First programme to evaluate dual HIV maintenance therapy with dolutegravir and rilpivirine

ViiV Healthcare today announced the start of a Phase III clinical trial programme to evaluate the safety and efficacy of dolutegravir (Tivicay(R)) and rilpivirine (Edurant(R)[1]) as maintenance therapy for adult patients with HIV. The Phase III programme comprises two replicate studies evaluating 48 week viral suppression with a two drug regimen combining an integrase inhibitor (dolutegravir) and a non-nucleoside reverse transcriptase inhibitor (rilpivirine) in patients with HIV who have already achieved viral suppression with a three drug regimen.

"As HIV care becomes an increasingly long term consideration, patients and clinicians are seeking to balance efficacy and side effects of treatment. We are able to attain initial viral suppression with a standard three drug regimen and the question is whether we can maintain viral suppression with two drugs instead of three." said Dr John Pottage, Chief Scientific and Medical Officer, ViiV Healthcare. "An interesting part of this Phase III programme is the inclusion of measures of the patient experience -- we're looking at health-related quality of life and adherence to treatment, in addition to the primary efficacy and safety endpoints."

In June 2014, ViiV Healthcare and Janssen Sciences Ireland UC, one of the Janssen Pharmaceutical Companies of Johnson & Johnson announced a partnership to investigate the potential of combining dolutegravir and rilpivirine in a single-tablet in order to expand the treatment options available to people living with HIV (ViiV Healthcare announces new collaboration with Janssen [http://www.viivhealthcare.com/media/press-releases/2014/june/viiv-healthcare-announces-new-collaboration-with-janssen.aspx] ).

About the Phase III programme

The Phase III programme will evaluate the efficacy, safety, and tolerability of switching to dolutegravir plus rilpivirine from current INI-,NNRTI-, or PI-based antiretroviral regimen in HIV-1-infected adults who are virologically suppressed. In the clinical trials, dolutegravir and rilpivirine will be provided as individual tablets; development of the single-tablet formulation will be concurrent with conduct of the trials.

SWORD-1 (NCT02429791) and SWORD-2 (NCT02422797) are replicate 148-week, randomised, open-label, non-inferiority studies to assess the antiviral activity and safety of a two-drug regimen of DTG + RPV compared with current antiretroviral therapy. Each study seeks to enrol approximately 500 patients across 13 countries and aims to enrol meaningful numbers of patients from groups underrepresented in HIV clinical studies, such as women and people over 50 years of age.

The primary endpoint is proportion of patients with plasma HIV-1 RNA <50 copies per milliliter (c/mL) at Week 48. Key secondary endpoints include evaluation of the development of viral resistance, measurements of safety and tolerability, and changes in renal, bone and cardiovascular biomarkers. The study will also include exploratory measures to assess change in health-related quality of life, willingness to switch, and adherence to treatment regimens.

For more information on the trials please visit: http://www.clinicaltrials.gov

Important Information about Tivicay(R) (dolutegravir) in the US

FDA Indication 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.

Use of TIVICAY in INSTI-experienced patients should be guided by the number and type of baseline INSTI substitutions. The efficacy of TIVICAY 50 mg twice daily is reduced in patients with an INSTI-resistance Q148 substitution plus 2 or more additional INSTI-resistance substitutions including T66A, L74I/M, E138A/K/T, G140S/A/C, Y143R/C/H, E157Q, G163S/E/K/Q, or G193E/R.

Important Safety Information for Tivicay(R) (dolutegravir)

Contraindication: TIVICAY is contraindicated (1) in patients with previous hypersensitivity reaction to dolutegravir, and (2) in patients receiving dofetilide (antiarrhythmic) 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 characterized 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. Discontinue TIVICAY and other suspect agents immediately 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 is contraindicated in patients who have experienced a hypersensitivity reaction to dolutegravir.

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 (greater than or equal to2%) adverse reactions of moderate to severe intensity in treatment naive adult subjects in any one trial receiving TIVICAY in a combination regimen were insomnia (3%), fatigue (2%), 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 taken2 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.

How TIVICAY Works TIVICAY belongs to a class of HIV medicines called integrase inhibitors. 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.

About ViiV Healthcare ViiV Healthcare is a global specialist HIV company established in November 2009 by GlaxoSmithKline and Pfizer 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 http://www.viivhealthcare.com.

Important Information about EDURANT(R)(rilpivirine)

EDURANT(R) (rilpivirine) is a prescription HIV medicine that is used with other antiretroviral medicines to treat Human Immunodeficiency Virus-1 (HIV-1) in adults:

- Who have never taken HIV medicines before and
- Who have an amount of HIV in their blood (called "viral load") that is no more
  than 100,000 copies/mL. Your healthcare professional will measure your viral load
 

EDURANT(R) should be taken in combination with other HIV medicines. Your healthcare professional will work with you to find the right combination of HIV medicines

It is important that you remain under the care of your healthcare professional during treatment with EDURANT(R)

EDURANT(R) is not recommended for patients less than 18 years of age

EDURANT(R) does not cure HIV infection or AIDS. You should remain on your HIV medications without stopping to ensure that you control your HIV infection and decrease the risk of HIV-related illnesses. Ask your healthcare professional about how to prevent passing HIV to other people.

Important Safety Information for EDURANT(R) (rilpivirine)

Can EDURANT(R) betaken withother medicines?

EDURANT(R) may affect the way other medicines work and other medicines may affect how EDURANT(R) works and may cause serious side effects. If you take certain medicines with EDURANT(R), the amount of EDURANT(R) 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(R) or other HIV medicines that are like it. To help get the right amount of medicine in your body, you should always take EDURANT(R) with a meal. A protein drink alone does not replace a meal.

Do not take EDURANT(R) if:

- Your HIV infection has been previously treated with HIV medicines
- You are taking any of the following medicines:
     - Anti-seizure medicines: carbamazepine (Carbatrol(R), Equetro(R),
     Tegretol(R), Tegretol-XR(R), Teril(R), Epitol(R)), oxcarbazepine (Trileptal(R)),
     phenobarbital (Luminal(R)), phenytoin (Dilantin(R), Dilantin-125(R), Phenytek(R))
     - Anti-tuberculosis (anti-TB) medicines: rifampin (Rifater(R), Rifamate(R),
     Rimactane(R), Rifadin(R)), rifapentine (Priftin(R))
     - Proton pump inhibitor (PPI) medicine for certain stomach or intestinal
     problems: esomeprazole (Nexium(R), Vimovo(R)), lansoprazole (Prevacid(R)),
     omeprazole (Prilosec(R), Zegerid(R)), pantoprazole sodium (Protonix(R)),
     rabeprazole (Aciphex(R))
     - 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(R), 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(R)
- Medicines to block acid in your stomach, including cimetidine (Tagamet(R)),
  famotidine (Pepcid(R)), nizatidine (Axid(R)), or ranitidine hydrochloride (Zantac(R)).
  Take these medicines at least 12 hours before or at least 4 hours after you take
  EDURANT(R)
 

This is not a complete list of medicines. Before starting EDURANT(R), 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(R), 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(R) will harm your unborn baby. You and your healthcare professional will need to decide if taking EDURANT(R) is right for you.

- Do not breastfeed if you are taking EDURANT(R). 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(R)?

EDURANT(R) 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(R) 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(R) 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 http://www.fda.gov/medwatch, or call1-800-FDA-1088.

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

About Edurant(R) (rilpivirine)

Rilpivirine was developed by Janssen Sciences Ireland UC, one of the Janssen Pharmaceutical Companies of Johnson & Johnson. Rilpivirine is a tablet dosed at 25mg taken once a day in combination with other antiviral agents. The overall safety profile of rilpivirine is based on Phase III clinical studies. In the rilpivirine arm, the most frequently reported adverse drug reactions (greater than or equal to 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(R) (US) or EVIPLERA(R), 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.

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 2014.

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1. Edurant(R) is a registered trademark of Janssen Janssen Sciences Ireland UC.

Contact:

Contacts: ViiV UK/US Media enquiries: Sebastien Desprez,
+44(0)7920-567-707; Marc Meachem, +1-919-483-8756; GSK Global Media
enquiries: Kathleen Cuca, +1-215-859-1922; David Daley,
+44(0)20-8047-5502;
Melinda Stubbee, +1-919-483-2510; Analyst/Investor enquiries: Ziba
Shamsi,
+44(0)20-8047-5543; Tom Curry, +1-215-751-5419; Gary Davies,
+44(0)20-8047-5503; James Dodwell, +44(0)20-8047-2406; Jeff
McLaughlin,
+1-215-751-7002


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