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

PR60404

LONDON, May 6 /PRN=KYODO JBN/ --

- 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 (＞＝2%) 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 (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

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 (＞＝

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.

Source: ViiV Healthcare