Janssen Presents Switch Data for New HIV-1 Treatment SYMTUZA™ (D/C/F/TAF) and Second Study Supporting its Use in a Rapid Initiation Scenario

Phase 3 EMERALD and DIAMOND studies at AIDS 2018 reinforce the safety and efficacy of SYMTUZA^TM (darunavir 800 mg, cobicistat 150 mg, emtricitabine 200 mg and tenofovir alafenamide 10 mg), the first darunavir-based HIV-1 single-tablet regimen

Amsterdam, The Netherlands, [July 24, 2018] – The Janssen Pharmaceutical Companies of Johnson & Johnson today announced new data reinforcing the safety and efficacy of switching to SYMTUZA^TM (D/C/F/TAF) for the treatment of HIV-1 regardless of prior treatment regimen among treatment-experienced patients. Data presented from another Phase 3 study also provide evidence to support a darunavir-based regimen when rapidly initiating treatment in people who are newly diagnosed with HIV-1.

Analyses from the pivotal Phase 3 EMERALD trial further support the efficacy and safety of switching from boosted protease inhibitor-based (bPI) regimens to D/C/F/TAF for the treatment of HIV-1 regardless of prior treatment regimen in virologically suppressed, treatment-experienced adults as previously published in The Lancet. Results from EMERALD showed similar virologic response rates at Week 48 (HIV-1 RNA <50 copies/mL: 95% vs 94%; HIV-1 RNA ≥50 copies/mL: 1% vs 1%) and rates of virologic rebound (2.5% vs 2.1%) were demonstrated with D/C/F/TAF compared to continuation of previous treatment in the overall population.

In the new analyses, data is presented in subgroups according to baseline regimen. Results were consistent across subgroups based on bPI regimens used at screening. The EMERALD trial investigates the proportion of patients with virologic rebound cumulative through Week 48.

“Forty-eight-week data from the pivotal EMERALD trial demonstrate continued virologic control following a switch to treatment with SYMTUZA^TM regardless of the individual’s previous boosted protease inhibitor-based regimen,” said Gregory Huhn, M.D., Infectious Disease Specialist, Cook County Health System, Chicago, Illinois. “These data add to the growing body of evidence that supports healthcare professionals to navigate treatment options.”

Additionally, interim results from the Phase 3 DIAMOND study provide evidence to support the use of a darunavir-based regimen when rapidly initiating treatment in newly diagnosed HIV-1 patients, as recommended by the U.S. Department of Health and Human Services guidelines.

DIAMOND is the first Phase 3 trial for a single-tablet regimen conducted in a rapid initiation scenario. In this study, no patients met predefined resistance stopping rules and 81% of patients achieved virologic suppression <50 copies/mL at Week 24 in an intent-to-treat (ITT) analysis. 90% of patients achieved virologic suppression <50 copies/ML at Week 24 based on as-observed analysis. Analysis at 24 Weeks is interim, and the primary endpoint will be at 48 Weeks. No patients stopped due to protocol-defined virologic failure, or lack of efficacy, and only one patient discontinued due to an adverse event.
DIAMOND is a single-arm pilot ongoing study to assess the efficacy and safety of D/C/F/TAF in a Test-and-Treat model over 48 weeks. In this study, adults diagnosed with HIV-1 infection within 14 days were immediately enrolled and started on D/C/F/TAF without screening/baseline laboratory or HIV genotypic resistance information. Screening/baseline laboratory and resistance findings were reviewed by investigators as results became available and patients not meeting predefined safety or resistance stopping rules continued treatment.

“HIV drug resistance and rapid initiation of treatment are key issues in today’s HIV care landscape,” said Brian Woodfall, M.D. Vice President, Global Head, Late Development, Infectious Diseases & Vaccines, Janssen Pharmaceutica NV. “We are committed to developing treatments for HIV that address key real-world challenges such as these. SYMTUZA^TM provides an important new option for people living with HIV.”

SYMTUZA^TM was approved by the U.S. FDA on July 17, 2018. It received European Commission approval in September 2017.

About EMERALD
EMERALD (NCT02269917) is a Phase 3, randomized (2:1), non-inferiority trial among treatment-experienced, virologically suppressed HIV-1–infected adults with viral load (VL) <50 copies/mL for ≥2 months (one 50≤VL<200 copies/mL allowed in prior 12 months). Previous non-darunavir virologic failure is allowed. The primary endpoint is the proportion of patients with virologic rebound (confirmed VL ≥50 copies/mL or premature discontinuation with last VL ≥50 copies/mL) cumulative through Week 48. Virologic response at Week 48 was VL <50 copies/mL (FDA snapshot). Safety was assessed by adverse events (AEs). Results were evaluated in subgroups based on bPI (darunavir [with ritonavir or cobicistat] vs atazanavir [with ritonavir or cobicistat] or lopinavir [with ritonavir]) and boosting agent (ritonavir vs cobicistat) used at baseline. A total of 1141 patients were randomized and treated. At screening, use of darunavir (70% of patients) was more common than atazanavir or lopinavir (30% combined), and boosting with ritonavir (85%) was more common than cobicistat (15%). Fifty eight percent had prior exposure to ≥5 ARVs and 15% had experienced prior VF. Results showed that virologically suppressed, treatment-experienced HIV-1–infected adults who switched to D/C/F/TAF had low, non-inferior cumulative virologic rebound rates versus continuation of prior therapy. In the overall population, similar rates of virologic rebound and virologic response were seen with D/C/F/TAF regardless of previous regimen. No patients developed resistance to study drugs.
For more information on this clinical trial, please visit: www.clinicaltrials.gov

About DIAMOND
DIAMOND (NCT03227861) is an ongoing, Phase 3, single‐arm, open‐label, prospective, multicenter study assessing the efficacy/safety of D/C/F/TAF 800/150/200/10 mg in a rapid initiation scenario over 48 weeks. Adults diagnosed with HIV‐1 infection within 14 days were immediately enrolled and started on D/C/F/TAF without screening/baseline laboratory or HIV genotypic resistance information available. Investigators reviewed screening/baseline laboratory and resistance findings as results became available; patients not meeting predefined safety or resistance stopping rules continued treatment. At the Week 24 interim analysis, 91% (99/109) of patients continued on D/C/F/TAF and only 10/109 discontinued (3 due to safety stopping rules, 3 lost to follow up, 2 withdrew consent, 1 protocol violation, 1 adverse event [AE]). No patients were required to discontinue treatment due to resistance stopping rules. At Week 24, in an Intent-to-Treat analysis, 88 of 109 (81%) patients had achieved HIV-1 RNA <50 copies/mL (FDA snapshot), no participants experienced protocol-defined virologic failure, or discontinued due to lack of efficacy. Most adverse events were Grade 1 or Grade 2 and only one participant discontinued treatment due to an adverse event. No serious adverse events related to study drug were reported.

The DIAMOND study was not included in the data submission package for U.S. FDA approval.

For more information on this clinical trial, please visit: www.clinicaltrials.gov

Further details on our work in HIV and the breadth of science being driven by Johnson & Johnson companies and their partners is available at jnj.com/HIV.

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Notes to editors
About SYMTUZA^TM

SYMTUZA^TM is a prescription human immunodeficiency virus type 1 (HIV-1) medicine used to treat HIV-1 infection in adults who have not received HIV-1 medicines in the past, or when their healthcare provider determines that they meet certain requirements.

SYMTUZA^TM is a fixed-dose combination of four active substances (darunavir, cobicistat, emtricitabine and tenofovir alafenamide), available as 800 mg/150 mg/200 mg/10 mg film-coated tablets. Darunavir inhibits the HIV protease and prevents the formation of mature infectious virus particles. Emtricitabine and tenofovir alafenamide are substrates and competitive inhibitors of HIV reverse transcriptase. After phosphorylation, they are incorporated into the viral DNA chain, resulting in chain termination. Cobicistat enhances the systemic exposure of darunavir and has no direct antiviral effect.

IMPORTANT SAFETY INFORMATION

What is the most important information I should know about SYMTUZA™?

SYMTUZA™ can cause serious side effects including:

• Worsening of hepatitis B virus infection. Your healthcare provider will test you for hepatitis B virus (HBV) before starting treatment with SYMTUZA™. If you have HBV infection and take SYMTUZA™, your HBV may get worse (flare-up) if you stop taking SYMTUZA™.

• Do not stop taking SYMTUZA™ without first talking to your healthcare provider.
• Do not run out of SYMTUZA™. Refill your prescription or talk to your healthcare provider before your SYMTUZA™ is all gone.
• If you stop taking SYMTUZA™, your healthcare provider will need to check your health often and do blood tests regularly for several months to check your HBV infection or give you a medicine to treat your HBV infection. Tell your healthcare provider about any new or unusual symptoms you may have after you stop taking SYMTUZA™.

• Change in liver enzymes. People with a history of hepatitis B or C virus infection or who have certain liver enzyme changes may have an increased risk of developing new or worsening liver problems during treatment with SYMTUZA™. Liver problems can also happen during treatment with SYMTUZA™ 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 SYMTUZA™.
• Severe liver problems. In rare cases, severe liver problems can happen that can lead to death. Tell your healthcare provider right away if you get these symptoms:

• Skin or the white part of your eyes turn yellow
• Dark “tea-colored” urine
• Light-colored stools
• Loss of appetite for several days or longer
• Nausea
• Vomiting
• Stomach area pain

SYMTUZA™ may cause severe or life-threatening skin reactions or rashes which may sometime require treatment in a hospital. Call your healthcare provider right away if you develop a rash. Stop taking SYMTUZA™ and call your healthcare provider right away if you develop any skin changes with symptoms below:

• Fever
• Tiredness
• Muscle or joint pain
• Blisters or skin lesions
• Mouth sores or ulcers
• Red or inflamed eyes, like “pink eye” (conjunctivitis)

Who should not take SYMTUZA™?

• Do not take SYMTUZA™ with any of the following medicines: alfuzosin, carbamazepine, cisapride, colchicine (if you have liver or kidney problems), dronedarone, elbasvir and grazoprevir, ergot-containing medicines (such as: dihydroergotamine, ergotamine tartrate, methylergonovine), lovastatin or a product that contains lovastatin, lurasidone, oral midazolam (when taken by mouth), phenobarbital, phenytoin, pimozide, ranolazine, rifampin, St. John’s wort (Hypericum perforatum) or a product that contains St. John’s wort, sildenafil when used for pulmonary arterial hypertension (PAH), simvastatin or a product that contains simvastatin, or triazolam.
• Serious problems can happen if you take any of these medicines with SYMTUZA™.

Before taking SYMTUZA™, tell your healthcare provider about all of your medical conditions, including if you:

• have liver problems (including hepatitis B or hepatitis C), have kidney problems, are allergic to sulfa (sulfonamide), have diabetes, have hemophilia, or have any other medical condition.
• are pregnant (if you become pregnant while taking SYMTUZA™), or plan to become pregnant. It is unknown if SYMTUZA™ will harm your unborn baby.

• SYMTUZA™ should not be used during pregnancy.
• are breastfeeding or plan to breastfeed. Do not breastfeed if you take SYMTUZA™.

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Some medicines interact with SYMTUZA™. Keep a list of your medicines to show your healthcare provider and pharmacist. Do not start taking a new medicine without telling your healthcare provider.

How should I take SYMTUZA™?

• Take SYMTUZA™ 1 time a day with food.

What are the possible side effects of SYMTUZA™?

SYMTUZA™ may cause serious side effects including:

• See “What is the most important information I should know about SYMTUZA™?”
• Immune system changes can happen in people who start HIV medications.
• New or worse kidney problems, including kidney failure.

• Your healthcare provider should do blood and urine tests to check your kidneys before you start and while you are taking SYMTUZA™.
• Too much lactic acid in your blood (lactic acidosis).

• Too much lactic acid is a serious but rare medical emergency that can lead to death. Tell your healthcare provider right away if you get these symptoms: weakness or being more tired than usual, unusual muscle pain, being short of breath or fast breathing, stomach pain with nausea and vomiting, cold or blue hands and feet, feel dizzy or lightheaded, or a fast or abnormal heartbeat.
• Diabetes and high blood sugar (hyperglycemia). Some people who take protease inhibitors including SYMTUZA™ can get high blood sugar, develop diabetes, or your diabetes can get worse. Tell your healthcare provider if you notice an increase in thirst or if you start urinating more often while taking SYMTUZA™.
• Changes in body fat can happen in people taking HIV-1 medications.
• Increased bleeding can occur in people with hemophilia who are taking SYMTUZA™.

The most common side effects of SYMTUZA™ are: Diarrhea, rash, nausea, fatigue, headache, stomach problems, and gas.

These are not all of the possible side effects of SYMTUZA™.

Call your doctor for medical advice about side effects. You are encouraged to report negative 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, including Boxed Warning for SYMTUZA™.

About Janssen

At the Janssen Pharmaceutical Companies of Johnson & Johnson, we are working to create a world without disease. Transforming lives by finding new and better ways to prevent, intercept, treat and cure disease inspires us. We bring together the best minds and pursue the most promising science. We are Janssen. We collaborate with the world for the health of everyone in it. Janssen Pharmaceutica NV is one of the Janssen Pharmaceutical Companies of Johnson & Johnson. Learn more at www.janssen.com and follow us at @JanssenGlobal.

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 potential preventive and treatment regimens 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 the Janssen Pharmaceutical Companies and 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; uncertainty of commercial success for new indications and therapeutic combinations; competition, including technological advances, new products and patents attained by competitors; challenges to patents; product efficacy or safety concerns resulting in product recalls or regulatory action; changes in behaviour and spending patterns of purchasers of health care products and services; 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 Annual Report on Form 10-K for the year ended January 1, 2017, including under “Item 1A Risk Factors,” its most recently filed Quarterly Report on Form 10-Q, including in the section captioned “Cautionary Note Regarding Forward-Looking Statements,” 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.