Janssen Announces Results Of Two Phase 3 Studies Which Showed Long-Acting Injectable HIV Treatment Regimen Of Rilpivirine And Cabotegravir Demonstrated Comparable Safety And Efficacy To Daily Oral HIV Therapy

CORK, Ireland, March 7, 2019 /PRNewswire/ -- The Janssen Pharmaceutical Companies of Johnson & Johnson confirmed that the novel, investigational, long-acting two-drug injectable regimen of rilpivirine and cabotegravir met its primary endpoints in two major Phase 3 studies - the Antiretroviral Therapy as Long-Acting Suppression (ATLAS) trial and the First Long-Acting Injectable Regimen (FLAIR) trial. The positive 48-week results from both studies showed that Janssen's rilpivirine and ViiV Healthcare's cabotegravir, injected every four weeks, had similar efficacy in maintaining viral suppression in adults living with HIV-1 when compared to a standard of care, daily, oral three-drug regimen. These data were presented at the 2019 Conference on Retroviruses and Opportunistic Infections (CROI) in Seattle, Washington.  A livestream of the CROI press conference where these studies were highlighted can be viewed here: https://zoom.us/j/755218010 

"The Phase 3 results from these studies show that a two-drug injectable treatment regimen may provide people living with HIV the option of managing their virus with just 12 injection regimens a year. If approved by regulators, this will be the first monthly dosing solution for people living with HIV and represents a major step for HIV treatment," said Brian Woodfall, M.D., Global Head, Development, Infectious Diseases, Janssen Pharmaceutica NV.  "At Janssen, we are committed to the ongoing research and development of innovative solutions to fight HIV across the continuum of care. Using heart, science and ingenuity, we are partnering with others and utilizing our scale with the aim to make HIV history."

ATLAS

The global, pivotal, Phase 3 ATLAS study met its primary endpoint, with rilpivirine  and cabotegravir (long acting, or LA regimen) demonstrating non-inferiority to an oral three-drug regimen of two nucleoside reverse transcriptase inhibitors (NRTIs) plus a third agent on viral nonresponse, as measured by the proportion of patients with plasma HIV-1 RNA ≥50 copies per milliliter [c/mL] using the FDA Snapshot algorithm at Week 48 [LA regimen: 5/308 (1.6 percent), current antiretroviral therapy: (CAR) 3/308 (1.0 percent), adjusted difference: 0.6 percent, 95 percent confidence interval: -1.2, 2.5)].

The study found virologic suppression rates (HIV-1 RNA <50 c/mL) at Week 48 were similar between treatment arms [LA regimen: 285/308 (92.5 percent), CAR: 294/308 (95.5 percent), adjusted difference: -3 percent, 95 percent confidence interval: -6.7, 0.7].  Confirmed virologic failure (CVF) was infrequent.  Three patients (1 percent) who received the LA regimen developed CVF with subsequent identification of resistance mutations to one or both agents.  In two of these cases, pre-existing NNRTI resistance was identified. Two of the three individuals were from Russia and all three had HIV-1 A subtypes, which are seen frequently in Russia, Eastern Europe and East Africa; however, they are seen infrequently in other parts of the world. This unexpected pattern warrants further investigation. In the oral CAR arm, four participants developed CVF, three of whom developed drug resistance mutations.

Patient treatment satisfaction significantly improved after switching to the LA regimen from the previous oral therapy compared to remaining on oral therapy at Week 44 based on the HIV Treatment Satisfaction Questionnaire (HIVTSQs mean difference 5.68; 95 percent CI [4.37, 6.9]; p<0.001). Patient preference data from a single-item question administered at Week 48 showed that 266/308 (86.4 percent) preferred the long-acting injectable regimen whereas 7/308 (2.3 percent) preferred their previous oral therapy.

"The positive safety and efficacy results from the ATLAS study reinforce the potential of rilpivirine and cabotegravir as the first long-acting, injectable regimen option for people living with HIV," said Susan Swindells, MBBS, Professor, Department of Internal Medicine, Section of Infectious Diseases at the University of Nebraska Medical Center and ATLAS principal investigator.  "This novel approach may help alleviate the burden often associated with daily oral treatment regimens and contribute to making HIV a smaller part of people's lives."

Treatment with the LA regimen was generally well-tolerated, with low rates of serious adverse events (SAEs) [13/308 (4.2 percent)] and drug- or injection-related withdrawals. Of the patients who received the LA regimen, 83 percent (250/308) reported an injection site reaction (ISR) at some point through the 48-week study.  A majority of injections did not result in ISRs being reported; among a total of 6978 injections administered during the 48-week study, 1460 ISRs were reported. Most ISR events were mild [1156/1460 (79.2 percent)] and lasted an average of three days.  Four participants (1.3 percent) withdrew for injection-related events.

FLAIR

The global, pivotal, Phase 3 study met its primary endpoint, with the LA regimen demonstrating non-inferiority to Triumeq^® (abacavir/dolutegravir/lamivudine-ABC/DTG/3TC), as measured by the proportion of patients with plasma HIV-1 RNA ≥50 copies per milliliter [c/mL] using the FDA Snapshot algorithm at Week 48 [LA regimen: 6/283 (2.1 percent), Triumeq^® 7/283 (2.5 percent), adjusted difference: -0.4 percent, 95 percent confidence interval: -2.8, 2.1)].  The study found virologic suppression rates (HIV-1 RNA <50 c/mL) at Week 48 were similar between treatment arms [LA regimen: 265/283 (93.6 percent), Triumeq^®: 264/283 (93.3 percent), adjusted difference: 0.4 percent. 95 percent confidence interval: -3.7, 4.5].

Confirmed virologic failure (CVF) was infrequent across both treatment arms. Of the individuals who received the LA regimen, there were three confirmed virologic failures (approximately 1 percent), all of whom had treatment-emergent, NNRTI and INSTI resistance.  All of these individuals were from Russia and had HIV-1 subtype A1, which is seen frequently in Russia, Eastern Europe and East Africa; however, it is seen infrequently in other parts of the world. This unexpected pattern warrants further investigation. Three participants in the Triumeq^® arm developed CVF with no treatment emergent resistance.

Patient treatment satisfaction significantly improved after switching to the LA regimen from the previous oral therapy compared to remaining on oral therapy at Week 48 based on the HIV Treatment Satisfaction Questionnaire (HIVTSQc mean difference 4.1; 95 percent CI [2.8, 5.5], p<0.001). Patient preference data from a single-item question administered at Week 48 showed that 257/283 (90.8 percent) preferred the LA regimen whereas 2/283 (0.7 percent) preferred their previous oral therapy.

"The robust results of the FLAIR study lend further evidence to the potential of rilpivirine and cabotegravir as an alternative option for people currently on daily, oral therapy," said Chloe Orkin, M.D., Consultant Physician and Clinical Professor at Queen Mary University of London and FLAIR principal investigator. "This long-acting, two-drug regimen may provide an opportunity to change the paradigm for people living with HIV by breaking the cycle of daily pill taking, which has been a defining characteristic of HIV therapy for several decades."

Treatment with the LA regimen was generally well-tolerated, with low rates of SAEs [18/283 (6.4 percent)] and adverse events (AEs) leading to withdrawal [9/283 (3.2 percent)]. Of the patients who received the LA regimen, 86 percent (239/283) reported an ISR at some point through the 48-week study. A majority of injections did not result in an ISR being reported, with a total of 7704 injections administered during the 48-week study resulting in 2203 ISR events. Nearly all ISRs (99.4 percent) were mild or moderate (mild: 1907/2203, moderate: 282/2203), with a median duration of three days and the frequency of these events decreasing over time. Four participants (1.4 percent) withdrew for injection related events.

In addition to the once-monthly dosing schedule being evaluated in the ATLAS study, a study is ongoing to investigate the LA regimen administered every two months in the ATLAS-2M study. The company plans to use data from the FLAIR and ATLAS studies for future regulatory submissions.

This novel regimen is being co-developed as part of a collaboration with ViiV Healthcare.

About ATLAS (NCT02951052) 
The ATLAS study includes 616 men and women living with HIV and is being conducted at research centers in Argentina, Australia, Canada, France, Germany, Italy, Mexico, Russia, South Africa, South Korea, Spain, Sweden, and the United States.

ATLAS is a Phase 3, open-label, active-controlled, multicenter, parallel-group, non-inferiority study designed to assess the antiviral activity and safety of a two-drug regimen of long-acting, injectable rilpivirine and cabotegravir dosed once per month compared to continuation of current ART of two nucleoside reverse transcriptase inhibitors (NRTIs) plus an integrase inhibitor (INI), non-nucleoside reverse transcriptase inhibitor (NNRTI), or protease inhibitor (PI). The primary endpoint for ATLAS is the proportion of patients with plasma HIV-1 RNA ≥50 copies per milliliter [c/mL] using the FDA Snapshot algorithm at Week 48 (Missing, Switch, or Discontinuation = Failure, Intent-to-Treat Exposed [ITT-E] population).

For further information, please see https://clinicaltrials.gov/ct2/show/NCT02951052.

About FLAIR (NCT02938520)
FLAIR includes 566 men and women living with HIV and is being conducted at research centers in Canada, France, Germany, Italy, Japan, the Netherlands, Russia, South Africa, Spain, the United Kingdom, and the United States.

FLAIR is Phase 3, randomized, open-label, multicenter, parallel-group, non-inferiority study designed to assess the antiviral activity and safety of a two-drug regimen of intramuscular, long-acting, injectable rilpivirine and cabotegravir in virologically suppressed adults living with HIV, following 20 weeks of induction therapy with Triumeq^®. The primary endpoint for FLAIR is the proportion of patients with a 'virologic failure' endpoint as per the FDA Snapshot algorithm at Week 48 compared to those continuing Triumeq^® (Missing, Switch, or Discontinuation = Failure, Intent-to-Treat Exposed [ITT-E] population).

For further information, please see https://clinicaltrials.gov/ct2/show/NCT02938520.

About rilpivirine and rilpivirine long-acting
Rilpivirine is a non-nucleoside reverse transcriptase inhibitor (NNRTI) approved as EDURANT^® for the treatment of HIV in combination with other antiretrovirals and is being developed by Janssen Sciences Ireland UC in a long-acting formulation (Rilpivirine LA).  Rilpivirine LA is an investigational injectable nanoparticle suspension for intramuscular injection which is not approved by regulatory authorities anywhere in the world.

About cabotegravir 
Cabotegravir is an investigational integrase inhibitor (INI) and is not approved by regulatory authorities anywhere in the world. Cabotegravir is being developed by ViiV Healthcare for the treatment and prevention of HIV and is currently being evaluated as a long-acting, nanosuspension formulation for intramuscular injection and also as a once-daily oral tablet for induction prior to long-acting injection.

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 and follow us at www.twitter.com/JanssenGlobal. Janssen Pharmaceutica NV and Janssen Sciences Ireland UC are members of the Janssen Pharmaceutical Companies of Johnson & Johnson.

About Johnson & Johnson
At Johnson & Johnson, we believe good health is the foundation of vibrant lives, thriving communities and forward progress. That's why for more than 130 years, we have aimed to keep people well at every age and every stage of life. Today, as the world's largest and most broadly-based health care company, we are committed to using our reach and size for good. We strive to improve access and affordability, create healthier communities, and put a healthy mind, body and environment within reach of everyone, everywhere. We are blending our heart, science and ingenuity to profoundly change the trajectory of health for humanity.

Notice to Investors 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 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 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 30, 2018, 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.

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