PR67400

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

SEATTLE, Feb. 14, 2017 /PRNewswire=KYODO JBN/ --

    

       - 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(R)) and

rilpivirine (Edurant(R))  

    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(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 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(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 12 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.  

    Please read Important Safety Information below, and talk to your healthcare

professional to learn if EDURANT(R) is right for you.  

    Important Safety Information  

    Can EDURANT(R) be taken with other 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:  

＜start_indent＞

    

    - 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(R) 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).  

         - Any of these medicines (if taken by mouth or injection):

clarithromycin (Biaxin(R)), erythromycin (E-Mycin(R), Eryc(R), Ery-Tab(R),

PCE(R), Pediazole(R), Ilosone(R)), fluconazole (Diflucan(R)), itraconazole

(Sporanox(R)), ketoconazole (Nizoral(R)), methadone (Dolophine(R)),

posaconazole (Noxafil(R)), telithromycin (Ketek(R)), voriconazole (Vfend(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:

    

    - Severe skin rash and allergic reactions. Call your doctor right away if

you get a rash. Stop taking EDURANT(R) 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(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 side effects of prescription drugs to the FDA.

Visit http://www.fda.gov/medwatch, [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/prescribing-information-edurant.pdf ] for more

details.

    TIVICAY(R) (dolutegravir) tablets  

    Professional Indication(s) and Important Safety Information  

    Indications and Usage  

    TIVICAY(R) 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(R) in INSTI-experienced patients should be guided by the

number and type of baseline INSTI substitutions. The efficacy of TIVICAY(R)

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(R) 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(R) in

Phase 3 clinical trials.

    - Discontinue TIVICAY(R) 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(R). 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(R) 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 (greater than or equal to2%)

adverse reactions of moderate to severe intensity in treatment-naive adult

subjects in any one trial receiving TIVICAY(R) in a combination regimen were

insomnia (3%), fatigue (2%), and headache (2%).

    Drug Interactions:   

    

    - Coadministration of TIVICAY(R) with certain inducers of UGT1A and/or

CYP3A may reduce plasma concentrations of dolutegravir and require dose

adjustments of TIVICAY (R).

    - Administer TIVICAY(R) 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(R)

and supplements containing calcium or iron can be taken with food

    - Consult the full Prescribing Information for TIVICAY(R) for more

information on potentially significant drug interactions, including clinical

comments

    Pregnancy: TIVICAY(R) 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.

SOURCE: Janssen Sciences Ireland UC