ViiV Healthcare submits regulatory application to European Medicines Agency for investigational cabotegravir to be used in combination with rilpivirine as the first monthly, injectable treatment for HIV
The marketing application is based on phase III ATLAS and FLAIR pivotal trials in which the once-monthly, injectable treatment regimen showed similar efficacy and safety to daily, 3-drug oral treatment.
Issued: London, UK July 2019
ViiV Healthcare, the global specialist HIV company majority owned by GSK, with Pfizer Inc. and Shionogi Limited as shareholders, today announced the submission of a marketing authorisation application (MAA) to the European Medicines Agency (EMA) for the investigational, once-monthly, injectable cabotegravir, which will be used in combination with Janssen's once-monthly, injectable rilpivirine to treat HIV-1 infection in adults whose viral load is suppressed and who are not resistant to cabotegravir or rilpivirine. The application also includes data for cabotegravir oral tablets, intended for use as oral lead-in therapy prior to the commencement of injectable therapy.
Deborah Waterhouse, CEO of ViiV Healthcare, said: "ViiV Healthcare is proud to be sending a regulatory submission to the EMA for what will be a first-of-its-kind treatment. If approved, this long-acting, injectable regimen of cabotegravir and rilpivirine has the potential to give people living with HIV one month between doses with similar safety and efficacy as today's standard of care - an oral, 3-drug regimen taken every day. We are excited to be one step closer to delivering this long-acting therapy to patients in Europe."
The submission is based on the global ATLAS (Antiretroviral Therapy as Long-Acting Suppression) and FLAIR (First Long-Acting Injectable Regimen) pivotal phase III studies that included more than 1,100 patients from 16 countries and demonstrated the combination of cabotegravir and rilpivirine, injected monthly, was as effective as a daily, oral, 3-drug regimen in maintaining viral suppression throughout the 48-week study period. The ATLAS and FLAIR studies are part of ViiV Healthcare's innovative clinical trial programme for 2-drug regimens (2DRs).
Kimberly Smith, M.D., Head of Global Medical Research and Strategy at ViiV Healthcare, said: "This regulatory submission supports ViiV Healthcare's commitment to developing new and innovative options for people living with HIV to manage their virus. We are proud to be at the forefront of this innovation for patients by potentially changing the frequency of therapy from 365 days per year to just 12."
This application to the EMA follows the recent submission of a New Drug Application (NDA) for the 2DR of cabotegravir and rilpivirine, as well as cabotegravir oral tablets, to the US Food and Drug Administration (FDA) in April 2019. In June, this submission was granted a Priority Review Designation by the FDA with an expected action date of December 29, 2019. ViiV Healthcare and Janssen also plan to submit additional regulatory applications for cabotegravir and rilpivirine to other regulatory agencies in the coming months.
FLAIR (NCT02938520) is a phase III, randomised, open-label, multicentre, parallel-group, non-inferiority study designed to assess the antiviral activity and safety of a 2-drug regimen of intramuscular, long-acting, injectable cabotegravir and rilpivirine in virologically suppressed adults living with HIV, following 20 weeks of induction therapy with Triumeq (abacavir, dolutegravir and lamivudine tablets). The primary endpoint for FLAIR is the proportion of participants with plasma HIV-1 RNA ≥50 c/mL per the FDA Snapshot algorithm at Week 48 (Missing, Switch, or Discontinuation = Failure, Intent-to-Treat Exposed [ITT-E] population).
Important Safety Information (ISI) for EDURANT® (Rilpivirine)
Note: this is taken from the US label and local variations apply. Please refer to applicable local labelling.
About EDURANT® (Rilpivirine)
• EDURANT® (rilpivirine) is a prescription medicine that is used with other antiretroviral medicines to treat Human Immunodeficiency Virus-1 (HIV-1) in people 12 years of age and older and who weigh at least 77 lbs (35 kg):
• Have never taken HIV medicines before, and
• Have an amount of HIV in their blood (called "viral load") that is no more than 100,000 copies/mL
• EDURANT® is not recommended for patients less than 12 years of age or who weigh less than 77 lbs (35 kg)
IMPORTANT SAFETY INFORMATION
Who should not take EDURANT®?
Do not take EDURANT® if you also take:
• anti-seizure medicines:
• anti-tuberculosis (anti-TB) medicines:
• proton pump inhibitor (PPI) medicine for certain stomach or intestinal problems:
- pantoprazole sodium
• more than 1 dose of the steroid medicine dexamethasone or dexamethasone sodium phosphate
• John's wort (Hypericum perforatum)
What should I tell my healthcare provider before taking EDURANT®?
Before taking EDURANT®, tell your healthcare provider about all your medical conditions, including if you:
• have or had liver problems, including hepatitis B or C virus infection
• have kidney problems
• have ever had a mental health problem
• are pregnant or plan to become pregnant. It is not known if EDURANT® will harm your unborn baby. Tell your healthcare provider if you become pregnant during treatment with EDURANT®.
• are breastfeeding or plan to breastfeed. Do not breastfeed if you take EDURANT®.
◦ You should not breastfeed if you have HIV-1 because of the risk of passing HIV-1 to your baby.
◦ It is not known if EDURANT® passes into your breast milk. Talk with your healthcare provider about the best way to feed your baby during EDURANT®
Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.
Do not start taking a new medicine without telling your healthcare provider. Your healthcare provider can tell you if it is safe to take EDURANT® with other medicines.
How should I take EDURANT®?
• Take EDURANT® every day exactly as your healthcare provider tells you to.
• Take EDURANT® 1 time each day with a meal. A protein drink alone does not replace a meal.
• Do not change your dose or stop taking EDURANT® without first talking with your healthcare provider. Stay under the care of your healthcare provider during treatment with EDURANT®.
• Do not miss a dose of EDURANT®.
• If you take an H2-receptor antagonist (famotidine, cimetidine, nizatidine, or ranitidine), you should take these medicines at least 12 hours before or at least 4 hours after you take EDURANT®.
• If you take antacids, or other products that contain aluminum, calcium carbonate, or magnesium hydroxide, you should take these medicines at least 2 hours before or at least 4 hours after you take EDURANT®.
• If you miss a dose of EDURANT® within 12 hours of the time you usually take it, take your dose of EDURANT® with a meal as soon as possible. Then, take your next dose of EDURANT® at the regularly scheduled time. If you miss a dose of EDURANT® by more than 12 hours of the time you usually take it, wait and then take the next dose of EDURANT® at the regularly scheduled time.
• Do not take more than your prescribed dose to make up for a missed dose.
• If you take too much EDURANT®, call your healthcare provider or go to the nearest hospital emergency room right away.
What are the possible side effects of EDURANT®?
EDURANT® can cause serious side effects including:
• Severe skin rash and allergic reactions. Skin rash is a common side effect of EDURANT®. Skin rash can be serious. Call your healthcare provider right away if you get a rash. In some cases, rash and allergic reaction may need to be treated in a hospital.
If you get a rash with any of the following symptoms, stop taking EDURANT® and get medical help right away:
o fever o trouble breathing or swallowing
o skin blisters o pain on the right side of the stomach (abdominal) area
o mouth sores o dark-colored urine "tea colored"
o redness or swelling of the eyes (conjunctivitis)
o swelling of the face, lips, mouth, tongue, or throat
• Change in liver enzymes. 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 with EDURANT®. Liver problems have also happened during treatment with EDURANT® in people without a history of liver disease. Your healthcare provider may need to do tests to check your liver enzymes before and during treatment with EDURANT®.
• Depression or mood changes. Tell your healthcare provider 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
• Changes in body fat can happen in people who take HIV medicine. These changes may include increased amount of fat in the upper back and neck ("buffalo hump"), breast, and around the middle of your body (trunk). Loss of fat from the legs, arms, and face may also happen. The exact cause and long-term health effects of these problems are not known.
• Changes in your immune system (Immune Reconstitution Syndrome) can happen when you start taking HIV medicines. Your immune system may get stronger and begin to fight infections that have been hidden in your body for a long time. Tell your healthcare provider right away if you start having any new symptoms after starting your HIV-1 medicine.
The most 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 provider right away. Do not stop taking EDURANT® or any other medications without first talking to your healthcare provider.
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 accompanying full Product Information for more details.
Full US prescribing information including is available at:
For the EU Summary of Product Characteristics, please visit:
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 as a shareholder 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.
GSK is a science-led global healthcare company with a special purpose: to help people do more, feel better, live longer. For further information please visit www.gsk.com/about-us.
Cautionary statement regarding forward-looking statements
GSK cautions investors that any forward-looking statements or projections made by GSK, including those made in this announcement, are subject to risks and uncertainties that may cause actual results to differ materially from those projected. Such factors include, but are not limited to, those described under Item 3.D 'Principal risks and uncertainties' in the company's Annual Report on Form 20-F for 2018.