Janssen Announces Health Canada Approval of CABENUVA™, the First Long-Acting Regimen for the Treatment of HIV

Cork, Ireland, March 20, 2020 – The Janssen Pharmaceutical Companies of Johnson & Johnson today announced that Health Canada has approved CABENUVA™ (cabotegravir and rilpivirine extended release injectable suspensions), the first and only once-monthly, long-acting regimen for the treatment of HIV-1 infection in adults. CABENUVA™ is indicated as a complete regimen for the treatment of HIV-1 infection in adults to replace the current antiretroviral regimen in patients who are virologically stable and suppressed (HIV-1 RNA less than 50 copies per milliliter [mL]).

CABENUVA™, a co-packaged kit with two separate injectable medicines – Janssen’s rilpivirine and ViiV Healthcare’s cabotegravir – offers people living with HIV a new approach for maintaining viral suppression.¹ This novel regimen was co-developed as part of a collaboration with ViiV Healthcare and builds on Janssen’s 25-year commitment to make HIV history. ViiV Healthcare holds marketing authorization for CABENUVA™ in Canada.

“At Johnson & Johnson, we are dedicated to changing the course of the HIV epidemic through our pursuit of improved therapies and the development of an HIV vaccine,” said Paul Stoffels, M.D., Vice Chairman of the Executive Committee and Chief Scientific Officer of Johnson & Johnson. “The approval of CABENUVA™, the first once-monthly injectable treatment regimen, marks a historic step forward in that journey. We are proud to have brought forward an option for patients living with HIV to maintain viral suppression with just 12 treatments a year.”

The approval of CABENUVA™ is based on the pivotal Phase 3 ATLAS (Antiretroviral Therapy as Long-Acting Suppression) and FLAIR (First Long-Acting Injectable Regimen) studies that included more than 1,100 patients from 16 countries. The studies demonstrated that CABENUVA™ was as effective as continuing their daily, oral, antiretroviral regimens in maintaining viral suppression throughout the 48-week study period.

CABENUVA™ was preferred over their previous daily oral therapy by approximately nine out of 10 patients who switched to rilpivirine and cabotegravir long-acting in ATLAS and FLAIR studies. Treatment preference data was collected from ATLAS and FLAIR clinical trial participants who received CABENUVA™. In a pooled exploratory analysis of this Intent-to-Treat Exposed (ITT-E) population, 532 patients completed a single-item question at Week 48 (59 participants did not) and 88 percent (523/591) preferred CABENUVA™ compared with 2 percent (9/591) who preferred their previous antiretroviral (ARV) treatment. The results were descriptive in nature and are not intended to infer clinical significance.

In both ATLAS and FLAIR studies, the most common adverse reactions (Grades 1 to 4) observed in ≥2 percent of patients receiving CABENUVA™ were injection site reactions, pyrexia, fatigue, headache, musculoskeletal pain, nausea, sleep disorders, dizziness, rash and diarrhea. Over the 48-week study period, a total of 4 percent of participants discontinued CABENUVA™ due to adverse events. The New England Journal of Medicine published the 48-week results of these studies in its March 4, 2020 issue.

“The once-monthly injections of CABENUVA™ showed comparable efficacy to daily oral antiretroviral treatment in maintaining viral suppression,” said David Alain Wohl*, M.D., Professor of Medicine, Division of Infectious Diseases, University of North Carolina. “Continued advances like CABENUVA™ are truly a paradigm shift in treatment for those living with HIV.”

The rilpivirine and cabotegravir long-acting injectable regimen is currently under review by the European Medicines Agency (EMA) and regulatory authorities in Switzerland and Australia. Several additional submissions are planned throughout 2020. Janssen will also work closely with ViiV and the FDA to determine the appropriate next steps for a New Drug Application in the US.

*Dr. David Alain Wohl has served as a paid consultant for Janssen. He has not been compensated for any media work.

About CABENUVA™ (cabotegravir and rilpivirine extended release injectable suspensions)
CABENUVA™ is indicated in Canada as a complete regimen for the treatment of HIV-1 infection in adults to replace the current antiretroviral regimen in patients who are virologically stable and suppressed (HIV-1 RNA less than 50 copies/mL). CABENUVA™ is administered intramuscularly as two individual injections in the buttocks once a month by a healthcare provider.

CABENUVA™ should not be used in patients with known or suspected resistance to cabotegravir or rilpivirine.

The complete regimen combines rilpivirine, a non-nucleoside reverse transcriptase inhibitor (NNRTI) developed by Janssen Sciences Ireland Unlimited Company, with the integrase strand transfer inhibitor (INSTI) cabotegravir, developed by ViiV Healthcare.

INSTIs, like cabotegravir, inhibit HIV replication by preventing the viral DNA from integrating into the genetic material of human immune cells (T-cells). This step is essential in the HIV replication cycle and is also responsible for establishing chronic infection. Rilpivirine is an NNRTI that works by interfering with an enzyme called reverse transcriptase, which in turn stops the virus from multiplying.

Each of these medicines are also approved as once-daily oral tablets for use as a lead-in, to establish the tolerability of cabotegravir and rilpivirine prior to CABENUVA™ injection. Once-daily oral rilpivirine and cabotegravir tablets may also be used for up to two months in place of monthly injectable CABENUVA™ therapy when injectable doses are missed. The oral formulation of rilpivirine is also approved for the treatment of HIV-1 infection in combination with other antiretroviral agents in antiretroviral treatment-naïve patients 12 years of age and older and weighing at least 35 kg with a viral load ≤ 100,000 HIV RNA copies/mL.

Trademarks are owned by or licensed to Janssen and the ViiV Healthcare group of companies. ViiV Healthcare holds marketing authorization for CABENUVA™ in Canada.

About ATLAS and FLAIR
ATLAS (NCT02951052) is a Phase 3, open-label, active-controlled, multicenter, parallel-group, non-inferiority study designed to assess the antiviral activity, safety and tolerability of a two-drug regimen of long-acting, injectable rilpivirine and cabotegravir dosed every four weeks compared to continuation of current oral antiretroviral therapy (ART) of two nucleoside reverse transcriptase inhibitors (NRTIs) plus an integrase strand transfer inhibitor (INSTI), non-nucleoside reverse transcriptase inhibitor (NNRTI), or protease inhibitor (PI) among virally suppressed individuals. Patients were required to be virally suppressed for six months or longer, on a first or second regimen, with no prior failure. The primary endpoint for ATLAS is the proportion of participants with plasma HIV-1 RNA ≥50 c/mL per the U.S. FDA Snapshot algorithm at Week 48 (Missing, Switch, or Discontinuation = Failure, Intent-to-Treat Exposed [ITT-E] population).

FLAIR (NCT02938520) is a Phase 3, randomized, open-label, multicenter, parallel-group, non-inferiority study designed to assess the antiviral activity, safety and tolerability of a two-drug regimen of intramuscular, long-acting, injectable rilpivirine and cabotegravir in adults living with HIV who were virologically suppressed following 20 weeks of induction therapy with either dolutegravir/abacavir/lamivudine or dolutegravir plus 2 other NRTIs if patients were HLA-B*5701 positive. Patients who were virologically suppressed (HIV-1 RNA less than 50 copies/mL) were then randomized (1:1) to receive either a cabotegravir plus rilpivirine regimen or remain on the current antiretroviral regimen. 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 for CABENUVA™ (cabotegravir and rilpivirine extended release injectable suspensions)

Indications and clinical use:
CABENUVA™ (cabotegravir and rilpivirine extended release injectable suspensions) is indicated as a complete regimen for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in adults to replace the current antiretroviral regimen in patients who are virologically stable and suppressed (HIV-1 RNA <50 copies/mL).

VOCABRIA (cabotegravir tablets) is indicated, in combination with EDURANT^® (rilpivirine tablets), as a complete regimen for short-term treatment of human immunodeficiency virus type 1 (HIV-1) infection in adults who are virologically stable and suppressed (HIV-1 RNA <50 copies/mL) as: An oral lead-in to assess tolerability of cabotegravir prior to initiating CABENUVA™

• Oral bridging therapy for missed CABENUVA™ injections

Geriatrics (>65 years of age): Not sufficiently studied to determine if they respond differently than patients <65 years of age.

Pediatrics (<18 years of age): Safety and efficacy not established

Contraindications:
In combination with:

• Anticonvulsants: Carbamazepine, oxcarbazepine, phenobarbital, and phenytoin

• Antimycobacterials: Rifabutin, rifampin, rifapentine

• Glucocorticoid: Systemic dexamethasone (more than a single dose)

• St John’s wort (Hypericum perforatum)

Relevant warnings and precautions:

• Should not be used in patients with known or suspected resistance to cabotegravir or rilpivirine

• Patients may still develop opportunistic infections and other complications of HIV infection

• Risk of transmission: precautions should be taken

• Depressive disorders

• Hepatotoxicity (serum transaminase elevations)

• Hepatic adverse events; increased risk for worsening or development of transaminase elevations in patients with hepatitis B or C co-infection or marked elevations in transaminases prior to treatment; monitoring of liver chemistries is recommended

• Loss of virologic response due to drug interactions; review concomitant medications during therapy

• Caution when used in combination with drugs that have a risk of Torsade de Pointes

• Skin and hypersensitivity reactions; discontinue immediately if signs or symptoms develop

• Administer the oral lead-in dosing prior to administration of CABENUVA™ to help identify patients who may be at risk of a hypersensitivity reaction

• Residual concentrations of cabotegravir and rilpivirine injections may remain in the systemic circulation of patients for up to 12 months or longer

• Risk of resistance due to treatment discontinuation

• Post-injection reactions within minutes after the injection of rilpivirine, including dyspnea, agitation, abdominal cramping, flushing, sweating, oral numbness, and changes in blood pressure. Reported in <0.5% of subjects and began to resolve minutes after the injection, and may have been associated with inadvertent (partial) IV administration

• Insufficient data in pregnant women; should not be used unless the potential benefits outweigh the potential risks

• HIV-1-infected mothers should not breastfeed their infants if receiving CABENUVA™

About the Janssen Pharmaceutical Companies of Johnson & Johnson
At Janssen, we’re creating a future where disease is a thing of the past. We’re the Pharmaceutical Companies of Johnson & Johnson, working tirelessly to make that future a reality for patients everywhere by fighting sickness with science, improving access with ingenuity, and healing hopelessness with heart. We focus on areas of medicine where we can make the biggest difference: Cardiovascular & Metabolism, Immunology, Infectious Diseases & Vaccines, Neuroscience, Oncology, and Pulmonary Hypertension.

Learn more at www.janssen.com. Follow us at www.twitter.com/JanssenGlobal. Janssen Sciences Ireland Unlimited Company is part of the Janssen Pharmaceutical Companies of Johnson & Johnson.

Cautions Concerning Forward-Looking Statements
This press release contains “forward-looking statements” as defined in the Private Securities Litigation Reform Act of 1995 regarding rilpivirine and 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 Janssen Sciences Ireland Unlimited Company, 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 research and development, including the uncertainty of clinical success and of obtaining regulatory approvals; uncertainty of commercial success; manufacturing difficulties and delays; 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 behavior 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 descriptions of these risks, uncertainties and other factors can be found in Johnson & Johnson’s Annual Report on Form 10-K for the fiscal year ended December 29, 2019, including in the sections captioned “Cautionary Note Regarding Forward-Looking Statements” and “Item 1A. Risk Factors,” and in the company’s most recently filed Quarterly Report on Form 10-Q, 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 nor Johnson & Johnson undertakes to update any forward-looking statement as a result of new information or future events or developments.

1. CABENUVA™ (cabotegravir and rilpivirine) Prescribing Information. Canada. Approval 2020.