Market Overview

ViiV Healthcare announces SWORD 100-week data for Juluca (dolutegravir/rilpivirine) at AIDS 2018

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Juluca, the first 2-drug regimen, once daily, single pill regimen,
maintains viral suppression through 100 weeks

ViiV Healthcare today presented 100-week results from its phase III
programme evaluating the safety and efficacy of switching
virologically-suppressed people living with HIV (PLHIV) from a three or
four-drug antiretroviral regimen to a 2-drug regimen of dolutegravir
(ViiV Healthcare) and rilpivirine (Janssen Sciences Ireland UC, part of
the Janssen Pharmaceutical Companies of Johnson & Johnson.)1
These results were presented at the 22nd International AIDS Conference
taking place 23-27 July 2018 in Amsterdam.

John C. Pottage, Jr., MD, Chief Scientific and Medical Officer, ViiV
Healthcare, commented, "As we progress further into a new era of HIV
treatment, these 100-week data from the SWORD studies add to the growing
evidence base for Juluca and 2-drug regimens. The results confirm the
ability of Juluca to maintain efficacy over a 100-week period and
importantly support that the long-term safety profile of this regimen is
consistent with the respective labels of the component medicines. This
100-week data should provide physicians with further confidence that
they may be able to reduce the number of antiretroviral drugs required
to effectively maintain virologic suppression in their patient's HIV."

In pooled data from the SWORD 1 and SWORD 2 studies, 89% (456/513) of
participants on the 2-drug regimen of dolutegravir and rilpivirine for
100 weeks (n=513) maintained viral suppression, with a viral load of
less than 50 copies/mL. A low rate of snapshot virologic non-response
was observed (n=13; 3%) and 6 participants met the confirmed virologic
withdrawal criterion. Three participants failed with NNRTI mutations,
one that had pre-existing NNRTI mutations at baseline developed
resistance to rilpivirine and was withdrawn; no participants developed
integrase inhibitor resistance. There were no new safety findings in the
second year of the study. A total 34 participants (7%) experienced
adverse events that led to withdrawal through week 100.1

In the ‘late switch' arm (n=477), where participants continued on their
current antiretroviral regimen until week 52 before switching to the
2-drug regimen of dolutegravir and rilpivirine, 93% (n=444) of
participants maintained viral suppression through week 100. Two
participants (<1%) met the confirmed virologic withdrawal criterion, and
the safety profile of the late switch group was comparable to the early
switch group (dolutegravir and rilpivirine from day 1 to week 100). 30
participants (6%) experienced serious adverse events and 15 participants
(3%) experienced adverse events that led to withdrawal.1

The SWORD clinical programme is part of ViiV Healthcare's ongoing
commitment to lessening the burden of HIV treatment on PLHIV through
research into 2-drug regimens. The 48-week results from the SWORD
studies were presented at CROI 2017 and later published in The Lancet.2
Data from the SWORD studies as well as a pivotal bioequivalence study3
has led to successful regulatory approval of the 2-drug regimen in the
United States, European Union, Canada and Australia, marketed under the
trade name Juluca.4,5,6,7

- 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 2013,8 but more can be done for
the estimated 36.7 million people living with HIV9 of which
160,000 were newly diagnosed in the Europe region alone in
2016.10

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

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 INIs
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.

About the SWORD phase III programme for Juluca

The SWORD phase III programme 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.11,12 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
2-drug, daily oral regimen of dolutegravir plus rilpivirine compared
with current antiretroviral therapy11,12 (the 148-week data
will be shared in 2019). In the SWORD clinical trials, dolutegravir and
rilpivirine are provided as individual tablets.11,12

The primary endpoint is the proportion of patients with plasma HIV-1 RNA
<50 copies per millilitre (copies/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.11,12

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

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

Edurant is a registered trademark of Janssen Sciences Ireland UC.

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 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 Aboud M, Orkin C, Podzamczer D, et al. Durable Suppression
2 years after switch to DTG+RPV 2-Drug Regimen: SWORD 1&2 Studies.
Presented at the 22nd International AIDS Conference (AIDS 2018), 23-27
July 2018, Amsterdam, The Netherlands.

2 Llibre JM, et al. Efficacy, safety, and tolerability of
dolutegravir-rilpivirine for the maintenance of virological suppression
in adults with HIV-1: phase 3, randomised, non-inferiority SWORD-1 and
SWORD-2 studies. The Lancet. 2018 Mar 3;391(10123):839-849.

3 Metha R, et al. Bioequivalence of a fixed dose combination
tablet of dolutegravir and rilpivirine in healthy subjects. Presented at
the 18th Workshop on Clinical Pharmacology of Antiviral Therapy, 2017.
Chicago, United States.

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.

8 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.

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

10 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.

11 SWORD-1 - Regimen Switch to Dolutegravir + Rilpivirine
From Current Antiretroviral Regimen in Human Immunodeficiency Virus Type
1 Infected and Virologically Suppressed Adults (SWORD-1). Available at: https://clinicaltrials.gov/ct2/show/NCT02429791?term=dolutegravir+AND+sword&cond=HIV&rank=3
Last accessed July 2018.

12 SWORD-2 - Regimen Switch to Dolutegravir + Rilpivirine
From Current Antiretroviral Regimen in Human Immunodeficiency Virus Type
1 Infected and Virologically Suppressed Adults (SWORD-2). Available at: https://clinicaltrials.gov/ct2/show/NCT02422797?term=dolutegravir+AND+sword&cond=HIV&rank=1
Last accessed July 2018.

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