Janssen Announces Two-drug Combination of Dolutegravir and Rilpivirine Demonstrates Efficacy in Maintaining Viral Suppression in Phase III Clinical Studies

Seattle (ots/PRNewswire) -

- First Detailed Results from SWORD Clinical Trial Program Show
Investigational Two-drug Combination as Effective as Three- or
Four-drug Regimens as Maintenance Therapy in Patients who have
Already Achieved Viral Suppression

Janssen Sciences Ireland UC (Janssen) announced positive results
from the full data read out for two Phase III studies evaluating the
safety and efficacy of switching virologically suppressed patients
from a three- or four-drug antiretroviral regimen to the two-drug
regimen of dolutegravir (ViiV Healthcare) and rilpivirine (Janssen).
Full results were presented at the annual Conference on Retroviruses
and Opportunistic Infections (CROI) in Seattle, WA.

(Logo: http://photos.prnewswire.com/prnh/20160223/336306LOGO )

If approved, this treatment could be the first two-drug regimen
for HIV and could offer those living with HIV who are virally
suppressed the option to switch to a regimen which does not include a
nucleotide reverse transcriptase inhibitor (NRTI).

The dolutegravir and rilpivirine regimen achieved non-inferior
viral suppression (HIV-1 RNA <50 c/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 (current antiretroviral therapy (CAR)
485/511 (95%), dolutegravir + rilpivirine 486/513 (95%) (adjusted
difference -0.2%, (95% CI: [3.0%, 2.5%]), pooled analysis). Virologic
suppression rates were similar between treatment arms. The median
duration of antiretroviral treatment was just over four years at the
time of entry into the studies. The most commonly reported (>5%)
adverse events in the dolutegravir and rilpivirine arm were
nasopharyngitis, headache, diarrhea and upper respiratory tract
infection. For the CAR arm, the most commonly reported adverse events
were nasopharyngitis, upper respiratory tract infection, back pain,
headache and diarrhea. The studies are ongoing for 148 weeks.

"The SWORD Phase III results represent an important step forward
in our efforts to deliver a two-drug regimen that may help simplify
dosing regimens and reduce pill burden for people living with HIV,"
says Lawrence M. Blatt, Global R&D Head, Infectious Diseases &
Vaccines, Janssen. "As HIV is increasingly treated as a life-long
condition, we remain committed to ongoing research and development of
further medicines to treat HIV more simply and to help all those
living with HIV to achieve an undetectable viral load and have an
improved quality of life."

Virologic failure rates were <1% in the DTG+RPV arm and 1% in the
three- or four- antiretroviral-drug arm. No integrase strand
inhibitor (INSTI) resistance-associated mutations were reported.
Protocol-defined virologic failure with a non-nucleoside
reverse-transcriptase inhibitor (NNRTI) resistance-associated
mutation (RAMs; K101K/E) was reported in only one patient in the
DTG+RPV arm in the context of documented non-adherence, but with no
impact on regimen efficacy as the subject re-suppressed on
dolutegravir and rilpivirine prior to withdrawal from the study.

The overall rate of serious adverse events was comparable between
treatment groups (DTG+RPV: 27, CAR: 21). As would be expected when
switching from a stable regimen to a new regimen (in most cases
containing two new drugs), more adverse events were reported and led
to withdrawal from the study in the DTG+RPV arm (DTG+RPV: 21, CAR:
3).

The safety profiles for dolutegravir and rilpivirine in these
studies were consistent with the product labelling for each medicine.

About the SWORD Phase III Program for dolutegravir (Tivicay®) and
rilpivirine (Edurant®)

The 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. In the clinical trials,
dolutegravir and rilpivirine are provided as individual tablets.
SWORD-1 (NCT02429791) and SWORD-2 (NCT02422797) are replicate
148-week, randomized, 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.

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 also includes 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

EDURANT® (Rilpivirine)

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

- 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® 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®.

EDURANT® is not recommended for patients less than 12 years of
age.

EDURANT® 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.

Please read Important Safety Information below, and talk to your
healthcare professional to learn if EDURANT® is right for you.

Important Safety Information

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:

- Severe skin rash and allergic reactions. Call your doctor right
away if you get a rash. Stop taking EDURANT® and seek medical help
right away if you get a rash with any of the following symptoms:
severe allergic reaction causing swelling of the face, eyes, lips,
mouth, tongue, or throat (which may lead to difficulty swallowing
or breathing); mouth sores or blisters on your body; inflamed eye
(conjunctivitis); fever; dark urine; or pain on the right side of
the stomach area (abdominal pain).
- 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 side effects of prescription drugs to
the FDA. Visit http://www.fda.gov/medwatch, or call 1-800-FDA-1088.
You may also report side effects to Janssen Products, LP at
1-800-JANSSEN (1-800-526-7736).

Please see full Product Information
(http://www.edurant.com/shared/product/Edurant/EDURANT-PI.pdf) for
more details.

TIVICAY® (dolutegravir) tablets

Professional Indication(s) and Important Safety Information

Indications 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
in adults and pediatric patients weighing at least 30 kg.

Limitations of Use:

- 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

Contraindications:

TIVICAY® is contraindicated in patients:

- with previous hypersensitivity reaction to dolutegravir
- receiving dofetilide (antiarrhythmic)

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% of subjects receiving TIVICAY® in Phase 3 clinical trials.
- Discontinue TIVICAY® and other suspect agents immediately if signs
or symptoms of hypersensitivity reactions develop, as a delay in
stopping treatment may result in a life-threatening reaction.
Monitor clinical status, including liver aminotransferases, and
initiate appropriate therapy if hypersensitivity reaction is
suspected.

Effects on Serum Liver Biochemistries in Patients with Hepatitis B
or C Co-infection:

- 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 or accumulation has been observed in patients
receiving antiretroviral therapy.

Immune Reconstitution Syndrome, including the occurrence of
autoimmune disorders with variable time to onset, has been reported.

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%), fatigue (2%), and headache (2%).

Drug Interactions:

- Coadministration of TIVICAY® with certain inducers of UGT1A and/or
CYP3A may reduce plasma concentrations of dolutegravir and require
dose adjustments of TIVICAY®.
- Administer TIVICAY® 2 hours before or 6 hours after taking
polyvalent cation-containing antacids or laxatives, sucralfate,
oral supplements containing iron or calcium, or buffered
medications. Alternatively, TIVICAY® and supplements containing
calcium or iron can be taken with food
- Consult the full Prescribing Information for TIVICAY® for more
information on potentially significant drug interactions, including
clinical comments

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

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

Cautions Concerning Forward-Looking Statements

This press release contains "forward-looking statements" as
defined in the Private Securities Litigation Reform Act of 1995
regarding development of treatment and prevention options for HIV.
The reader is cautioned not to rely on these forward-looking
statements. These statements are based on current expectations of
future events. If underlying assumptions prove inaccurate or known or
unknown risks or uncertainties materialize, actual results could vary
materially from the expectations and projections of Janssen Sciences
Ireland UC, any of the other Janssen Pharmaceutical Companies and/or
Johnson & Johnson. Risks and uncertainties include, but are not
limited to: challenges and uncertainties inherent in product
development, including uncertainty of clinical success and obtaining
regulatory approvals; competition, including technological advances,
new products and patents attained by competitors; challenges to
patents; changes to applicable laws and regulations, including global
health care reforms; and trends toward health care cost containment.
A further list and description of these risks, uncertainties and
other factors can be found in Johnson & Johnson's most recent Annual
Report on Form 10-K, including in Exhibit 99 thereto, and the
company's subsequent filings with the Securities and Exchange
Commission. Copies of these filings are available online at
http://www.sec.gov, http://www.jnj.com or on request from Johnson &
Johnson. None of the Janssen Pharmaceutical Companies or Johnson &
Johnson undertakes to update any forward-looking statement as a
result of new information or future events or developments.

ots Originaltext: Janssen Sciences Ireland UC
Im Internet recherchierbar: http://www.presseportal.de

Contact:
Katie Buckley
+44 7971 956 179
Kbuckle8@its.jnj.com | Kristina Chang
+1 201-213-4115
Kchang12@its.jnj.com | INVESTOR RELATIONS: Lesley Fishman
Phone: +1 732-524-3922
Joseph J. Wolk
Phone: +1 732-524-1142

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