Janssen Pharmaceutical Announces Submissions In Europe And U.S. For Single-Tablet Regimen Of Dolutegravir Plus Rilpivirine - The First Two-Drug HIV Maintenance Treatment

CORK, Ireland, June 1, 2017 /PRNewswire/ -- Janssen Sciences Ireland UC, today announced that ViiV Healthcare has made regulatory submissions to both the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA) for a single-tablet, two-drug regimen of dolutegravir (ViiV Healthcare) and rilpivirine (Janssen). If approved, this will be the first two-drug regimen for the maintenance treatment of HIV-1 infection and will 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 submissions are based on the Phase III SWORD studies which included more than one thousand patients who previously achieved viral suppression on a three or four drug antiretroviral regimen. The data were presented at the 2017 Conference on Retroviruses and Opportunistic Infections (CROI) in February.

A Priority Review voucher was submitted to the FDA along with the dolutegravir and rilpivirine two-drug regimen New Drug Application (NDA). Under the Prescription Drug User Fee Act, the anticipated target action date is six months after receipt of the application by the FDA.

"People living with HIV have always faced complex treatment regimens and a high pill burden. We know adherence is critically important for treatment outcomes and these regulatory submissions for dolutegravir plus rilpivirine represent a significant step forward in our efforts to deliver the first single-tablet, two-drug regimen for people living with HIV," said Lawrence M. Blatt, Global Therapeutic Area Head, Infectious Disease Therapeutics, Janssen. "If approved, this novel regimen will offer patients who are virally suppressed a safe and effective treatment option."  

Janssen have brought medicines to market across a range of patient populations that have helped to transform the efficacy and tolerability of treatment. In the US, approximately one in three people are managing their HIV with a treatment regimen containing a Janssen medicine.

Use of dolutegravir and rilpivirine as a two-drug regimen for HIV maintenance therapy is investigational and not approved anywhere in the world.

Notes to editors

In June 2014, ViiV Healthcare and Janssen Sciences Ireland UC, one of the Janssen Pharmaceutical Companies of Johnson & Johnson (Janssen) 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 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, 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. 

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 studies also include exploratory measures to assess change in health-related quality of life, willingness to switch, and adherence to treatment regimens.

About Janssen Pharmaceutical Companies of Johnson & Johnson

At Janssen, we are dedicated to addressing and solving some of the most important unmet medical needs of our time in oncology, immunology, neuroscience, infectious diseases and vaccines, and cardiovascular and metabolic diseases. Driven by our commitment to patients, we develop innovative products, services and healthcare solutions to help people throughout the world. Janssen Sciences Ireland UC is part of the Janssen Pharmaceutical Companies of Johnson & Johnson. Please visit http://www.janssenrnd.com for more information.

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

Tivicay is a registered trademark of the ViiV Healthcare group of companies
EDURANT^® is a registered trademark of Janssen Sciences Ireland UC

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 least4 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 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 for more details. http://www.edurant.com/shared/prescribing-information-edurant.pdf

TIVICAY (dolutegravir) tablets

Important Safety Information for TIVICAY^® (dolutegravir) 10-, 25-, and 50-mg tablets, for oral use

The following Important Safety Information (ISI) is based on the Highlights section of the US Prescribing Information for TIVICAY and local variations apply. Please consult the full Prescribing Information for all the labeled safety information for TIVICAY or please refer to applicable local labelling.

FDA 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 integrase strand transfer inhibitor (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.

CONTRAINDICATIONS

• Previous hypersensitivity reaction to dolutegravir.
• Coadministration with dofetilide.

WARNINGS AND PRECAUTIONS

• Hypersensitivity reactions characterized by rash, constitutional findings, and sometimes organ dysfunction, including liver injury, have been reported. 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.
• Patients with underlying hepatitis B or C may be at increased risk for worsening or development of transaminase elevations with use of TIVICAY. Appropriate laboratory testing prior to initiating therapy and monitoring for hepatotoxicity during therapy with TIVICAY is recommended in patients with underlying hepatic disease such as hepatitis B or C.
• Redistribution/accumulation of body fat and immune reconstitution syndrome have been reported in patients treated with combination antiretroviral therapy.

ADVERSE REACTIONS

The most common adverse reactions of moderate to severe intensity and incidence at least 2% (in those receiving TIVICAY in any one adult trial) are insomnia, fatigue, and headache.

DRUG INTERACTIONS

• Drugs that are metabolic inducers may decrease the plasma concentrations of dolutegravir.
• TIVICAY should be taken 2 hours before or 6 hours after taking 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 together with food.

USE IN SPECIFIC POPULATIONS

• Pregnancy: TIVICAY should be used during pregnancy only if the potential benefit justifies the potential risk.
• Lactation: Breastfeeding is not recommended.

Please visit the following link for the full US prescribing and patient information: https://www.gsksource.com/pharma/content/dam/GlaxoSmithKline/US/en/Prescribing_Information/Tivicay/pdf/TIVICAY-PI-PIL.PDF#page=1

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 www.sec.gov, 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.

MEDIA CONTACT:
Katie Buckley
+44 7971 956 179
kbuckle8@its.jnj.com

INVESTOR RELATIONS:   
Lesley Fishman
Phone: +1 732-524-3922

Joseph J. Wolk
Phone: +1 732-524-1142

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SOURCE Janssen