Janssen Reports Positive Topline Results For FLAIR Phase 3 Study Of A Novel, Long Acting Injectable Two-Drug Regimen For The Treatment Of HIV-1

- Dec 18, 2018-

The Janssen Pharmaceutical Companies of Johnson & Johnson today confirmed positive topline results from the global, Phase 3 FLAIR (First Long-Acting Injectable Regimen) study of a long-acting, injectable two-drug regimen (2DR) for the treatment of HIV.

The study, conducted by ViiV Healthcare, showed long-acting rilpivirine and cabotegravir, injected once a month, had similar efficacy to TRIUMEQ (abacavir/dolutegravir/lamivudine-ABC/DTG/3TC) based on the proportion of participants with plasma HIV-1 RNA ≥50 copies per millilitre [c/mL] using the FDA Snapshot algorithm at Week 48. Overall safety, virologic response and drug resistance results for the injectable regimen were consistent with results from the Phase 2 LATTE and LATTE-2 studies.

“These results offer further evidence to suggest that this investigational, two-drug, once a month dosing regimen may reduce the impact of treatment on people’s lives,” said Wim Parys, M.D., Head of R&D, Global Public Health, Janssen Pharmaceutica N.V. “This novel approach would signify a much-needed treatment evolution for people living with HIV, moving from dosing 365 to just 12 times per year.”

The FLAIR study was designed to establish whether adult participants infected with HIV-1, whose virus is suppressed after 20 weeks on the daily, oral medicine TRIUMEQ, remain suppressed at a similar rate to continuing TRIUMEQ after switching to the novel, two-drug long-acting regimen of rilpivirine and cabotegravir. Detailed results from the FLAIR study, co-funded by Janssen and ViiV Healthcare, will be presented at an upcoming scientific meeting.

Positive 160 Week Results from LATTE-2

At HIV Glasgow Drug Therapy Meeting in Scotland this week, three-year results were presented from LATTE-2, a Phase 2b study investigating a long-acting injectable, two-drug regimen of rilpivirine and cabotegravir, administered either every eight weeks or every four weeks. These results demonstrated high rates of virologic response, long-term durability of virologic response and good overall tolerability.

At 160 weeks, 90% (104/115) and 83% (95/115) of the patients receiving the injectable regimen of rilpivirine and cabotegravir every eight and four weeks, respectively, remained virally suppressed. Of the patients on the oral comparator arm who elected to switch to the injectable regimen at Week 96, 97% (33/34) and 100% (10/10) remained virally suppressed on every eight- and four-week dosing schedule, respectively, at Week 160. Through Week 48, two patients developed protocol-defined virologic failure (PVDF) on the every-eight-week dosing arm, one with treatment-emergent, non-nucleoside reverse transcriptase inhibitor (NNRTI) and integrase inhibitor (INI) resistance. No additional PVDF cases were observed on any arm between Week 48 and Week 160.

A majority of participants reported an injection site reaction (ISR) through Week 160, of which 85% were mild and 14% were moderate. Eighty-seven percent of ISRs resolved within seven days. Excluding ISRs, the most common adverse events (AEs) were nasopharyngitis (38%), diarrhoea (22%), and headache (22%). Three percent (3/115; Q8W) and 10% (12/115; Q4W) of patients had AEs leading to withdrawal or discontinuation and only 3/274 patients had ISRs leading to discontinuation through Week 160.

Further Studies of Novel Regimen

FLAIR is the second, Phase 3 clinical trial to examine the safety and efficacy of monthly dosing of injectable formulations of cabotegravir and rilpivirine. The ATLAS (Antiretroviral Therapy as Long Acting Suppression) study, for which positive headline data were reported in August 2018, compares a long-acting, injectable regimen against the continuation of current daily oral antiretroviral therapy in virologically suppressed, treatment-experienced patients. Pooled data from the FLAIR and ATLAS studies will be used for future regulatory submissions.

This novel regimen is being co-developed as part of a collaboration with ViiV Healthcare. Rilpivirine is approved as oral tablets and is investigational as an extended release suspension for injection.

About FLAIR (NCT02938520)

FLAIR is a Phase 3, randomised, open-label, multicentre, 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 participants 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/NCT0293852.

About LATTE-2 (NCT02120352)

LATTE-2 is a Phase 2b, multicentre, parallel-group, open-label study in antiretroviral therapy-naïve HIV-infected adults designed to test the antiviral activity, tolerability, and safety of two intramuscular dosing regimens of long-acting injectable rilpivirine and cabotegravir. After a 20-week induction period on oral cabotegravir and abacavir/lamivudine, suppressed patients were randomized 2:2:1 to receive the long-acting injectable rilpivirine and cabotegravir every eight weeks, every four weeks or to continue the oral cabotegravir and abacavir/lamivudine. After 96 weeks, treatment for patients on the long-acting, injectable regimen was extended through 160 weeks and patients on the oral regimen were given the option of transitioning to the long-acting regimen either every four or eight weeks. For further information please see https://clinicaltrials.gov/ct2/show/NCT02120352.

About Rilpivirine & 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 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. Learn more at www.janssen.com and follow us at @JanssenGlobal.