Juluca(R) (Dolutegravir and Rilpivirine) Approved in US as First 2-drug Regimen, Once-daily, Single Pill - a Complete Regimen for the Maintenance Treatment of Virologically Suppressed HIV-1 Infection

PR71175

LONDON, November 22, 2017 /PRNewswire=KYODO JBN/ --

ViiV Healthcare, the global specialist HIV company, majority owned by

GlaxoSmithKline, with Pfizer Inc. and Shionogi Limited as shareholders, today

announced that the US Food and Drug Administration (FDA) has approved

Juluca(R), indicated as a complete regimen for the maintenance treatment of

HIV-1 infection in adults who are virologically suppressed (HIV-1 RNA less than

50 copies per mL) on a stable antiretroviral (ART) regimen for at least six

months with no history of treatment failure and no known substitutions

associated with resistance to the individual components of Juluca.[1]

     (Logo: http://photos.prnewswire.com/prnh/20160223/336449LOGO )

Juluca is the first 2-drug regimen (2DR) comprising dolutegravir 50mg (ViiV

Healthcare), an integrase strand transfer inhibitor and rilpivirine 25mg

(Janssen Therapeutics, Division of Janssen Products LP), a non-nucleoside

reverse transcriptase inhibitor.

Deborah Waterhouse, CEO ViiV Healthcare said, "The FDA approval of Juluca marks

an important milestone in our commitment to deliver innovative advances in HIV

care by providing new treatment options that challenge the traditional approach

to care.  This is the start of a new era in HIV treatment. We are delighted to

be able to provide the first 2-drug regimen to physicians and people living

with HIV in the US, to support the reduction of long-term ART exposure as they

receive life-long treatment for their chronic condition."

This FDA approval is based primarily upon data from two pivotal phase III

clinical trials, SWORD-1[2] and SWORD-2,[2] which showed the 2-drug regimen

achieved non-inferior viral suppression (HIV-1 RNA less than 50 copies per mL)

at 48 weeks compared with a three- or four-drug regimen in both pooled and

individual analyses of the SWORD-1 and SWORD-2 studies (CAR 485/511 [95%],

dolutegravir + rilpivirine 486/513 [95%] [adjusted difference  -0.2% (95%

confidence interval CI: 3.0%, 2.5%), pooled analysis]).[2] Virologic

suppression rates were similar between treatment arms.[2]  Drug related adverse

events and adverse events leading to withdrawal occurred in low frequencies in

both arms of the study, but more frequently in the investigational arm.

John C Pottage, Jr, MD, Chief Scientific and Medical Officer, ViiV Healthcare,

commented, "Based on the fundamental principle that no one should have to take

more medicines than necessary, ViiV Healthcare has put in place a comprehensive

2-drug regimen research and development programme built around the

characteristics of dolutegravir. Juluca, our new 2-drug regimen, once-daily,

single pill, now provides people living with HIV who are virologically

suppressed, the option to reduce the number of antiretrovirals they take, while

maintaining the efficacy of a traditional three-drug regimen."

Juluca is the first medicine in our 2-drug regimen pipeline, which looks to

help lessen the lifetime burden of treatment for people living with HIV.  Our

R&D efforts are exploring the potential of two further 2-drug regimens both in

phase III development, a once-daily, single pill containing

dolutegravir/lamivudine for treatment naive patients, as well as

cabotegravir/rilpivirine long-acting injectable for treatment-experienced and

naive patients.

Notes to editors  

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.

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 leading to a 22% drop in global HIV mortality between

2009 and 2013,[3] but more can be done for the estimated 36.7 million people

living with HIV and 1.8 million individuals newly infected each year

worldwide.[4]

About Juluca

Juluca is a 2-drug regimen, once-daily, single pill that combines the INSTI

dolutegravir (50mg), with the NNRTI rilpivirine (25mg) taken once-daily as a

complete HIV regimen for people living with HIV who are virologically

suppressed.  

Two essential steps in the HIV life cycle include reverse transcription - when

the virus turns its RNA (ribonucleic acid) copy into DNA (deoxyribonucleic

acid) - and integration - the moment when viral DNA becomes part of the host

cell's DNA. These processes require two enzymes called nucleoside reverse

transcriptase and integrase. NNRTIs and INSTIs interfere with the action of

these two enzymes to prevent the virus from replicating. This decrease in

replication can lead to less virus being available to cause subsequent

infection of uninfected cells.

Juluca was approved by the US Food and Drug Administration (FDA) on 21st

November 2017, as a complete regimen for the treatment of HIV-1 infection in

adults who are virologically suppressed (HIV-1 RNA less than 50 copies per mL)

on a stable antiretroviral regimen for at least 6 months with no history of

treatment failure and no known substitutions associated with resistance to the

individual components of Juluca. Juluca is expected to be available in

pharmacies in the US from 11th December 2017.

ViiV Healthcare has also submitted regulatory marketing applications in Europe,

Canada, Australia and Switzerland.

About the SWORD phase III program for dolutegravir (Tivicay(R)) and rilpivirine

(Edurant(R))

The SWORD phase III program evaluates the efficacy, safety, and tolerability of

switching to dolutegravir plus rilpivirine from current integrase inhibitor-,

non-nucleoside reverse transcriptase inhibitor-, or boosted protease

inhibitor-based antiretroviral regimen in HIV-1-infected adults who are

virologically suppressed with a three or four-drug regimen. 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, daily oral regimen of dolutegravir plus rilpivirine compared

with current antiretroviral therapy (full 148-week data will be shared in

2018). In the SWORD clinical trials, dolutegravir and rilpivirine are provided

as individual tablets.

The primary endpoint is the proportion of patients with plasma HIV-1 RNA <50

copies per millilitre (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

studies 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

Juluca and Tivicay are registered trademarks of the ViiV Healthcare group of

companies.

*Edurant is a registered trademark of Janssen Sciences Ireland UC.

HIGHLIGHTS OF PRESCRIBING INFORMATION

These highlights do not include all the information needed to use JULUCA safely

and effectively. See full prescribing information for JULUCA.

JULUCA (dolutegravir and rilpivirine) tablets, for oral use Initial U.S.

Approval: 2017

INDICATIONS AND USAGE

JULUCA, a two-drug combination of dolutegravir, a human immunodeficiency virus

type 1 (HIV-1) integrase strand transfer inhibitor (INSTI), and rilpivirine, a

HIV-1 non-nucleoside reverse transcriptase inhibitor (NNRTI), is indicated 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 less than 50 copies per mL) on a stable antiretroviral regimen for at least

6 months with no history of treatment failure and no known substitutions

associated with resistance to the individual components of JULUCA.

DOSAGE AND ADMINISTRATION

One tablet taken orally once daily with a meal.

Rifabutin coadministration: Take an additional 25-mg tablet of rilpivirine with

JULUCA once daily with a meal for the duration of the rifabutin

coadministration.

DOSAGE FORMS AND STRENGTHS

Each tablet contains: 50 mg of dolutegravir (equivalent to 52.6 mg dolutegravir

sodium) and 25 mg of rilpivirine (equivalent to 27.5 mg rilpivirine

hydrochloride).

CONTRAINDICATIONS

Previous hypersensitivity reaction to dolutegravir or rilpivirine.

Coadministration with dofetilide.

Coadministration with drugs where significant decreases in rilpivirine plasma

concentrations may occur, which may result in loss of virologic response.

WARNINGS AND PRECAUTIONS

Severe skin and hypersensitivity reactions characterised by rash,

constitutional findings, and sometimes organ dysfunction, including liver

injury, have been reported with the individual components. Discontinue JULUCA

immediately if signs or symptoms of severe skin or hypersensitivity reactions

develop, as a delay in stopping treatment may result in a life-threatening

reaction.

Hepatotoxicity has been reported in patients receiving a dolutegravir- or

rilpivirine-containing regimen. Monitoring for hepatotoxicity is recommended.

Depressive disorders have been reported with the use of rilpivirine- or

dolutegravir-containing regimens. Immediate medical evaluation is recommended

for severe depressive symptoms.

ADVERSE REACTIONS

The most common adverse reactions (all Grades) observed in at least 2% of

subjects were diarrhoea and headache.

To report SUSPECTED ADVERSE REACTIONS, contact ViiV Healthcare at

1-888-844-8872 or FDA at 1-800-FDA-1088 or http://www.fda.gov/medwatch.

DRUG INTERACTIONS

Because JULUCA is a complete regimen, coadministration with other

antiretroviral medications for the treatment of HIV-1 infection is not

recommended.

Refer to the full prescribing information for important drug interactions with

JULUCA.

Drugs that induce or inhibit CYP3A4 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.

USE IN SPECIFIC POPULATIONS

Lactation: Breastfeeding is not recommended due to the potential for HIV

transmission.

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 http://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 http://www.gsk.com.

References

1. Juluca US label information

2. Llibre JM, Hung C-C, Brinson C, et al. SWORD 1 & 2: Switch to DTG + RPV

maintains virologic suppression through 48 weeks, a Phase III study. Presented

at: Conference on Retroviruses and Opportunistic Infections; February 13-16,

2017; Seattle, WA, USA.

3. 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 November 2017.

4. World Health Organization. HIV/AIDS Fact Sheet. Available at:

http://www.who.int/mediacentre/factsheets/fs360/en/. Last accessed November

2017.

ViiV Healthcare Media enquiries:    

Patricia O'Connor, +44-208-047-5982

Marc Meachem, +1-919-483-8756

GSK Global Media enquiries:    

Simon Steel, +44(0)20-8047-3763

David Daley, +44(0)20-8047-2615

Analyst/Investor enquiries:    

Sarah Elton-Farr, +44(0)20-8047-5194

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

SOURCE: ViiV Healthcare