Seattle, WA, 13 February 2017 – 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.
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: www.clinicaltrials.gov
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:
o Anti-seizure medicines: carbamazepine (Carbatrol®, Equetro®, Tegretol®, Tegretol-XR®, Teril®, Epitol®), oxcarbazepine (Trileptal®), phenobarbital (Luminal®), phenytoin (Dilantin®, Dilantin-125®, Phenytek®).
o 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®).
o More than 1 dose of the steroid medicine dexamethasone or dexamethasone sodium phosphate.
o St. John’s wort (Hypericum perforatum).
- Especially tell your doctor if you take:
o 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.
o Medicines used to treat HIV.
o 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®.
o 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®.
o 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.
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
TIVICAY® is contraindicated in patients:
- with previous hypersensitivity reaction to dolutegravir
- receiving dofetilide (antiarrhythmic)
- 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%).
- 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 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.
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Joseph J. Wolk
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