Positive Phase 3 Data for Darunavir-based Single Tablet Regimen for HIV

Yesterday, in an oral session at the 9th International AIDS Society Conference on HIV Science in Paris, Janssen-Cilag International NV announced that an investigational single-tablet regimen (STR) containing darunavir is effective and well tolerated.

Results from the pivotal Phase 3 EMERALD study showed that a once-daily STR containing darunavir 800 mg, cobicistat 150 mg, emtricitabine 200 mg and tenofovir alafenamide 10 mg [D/C/F/TAF] had a low cumulative virologic rebound rate and a high virologic suppression rate at 24 weeks in human immunodeficiency virus type 1 (HIV-1) positive, virologically suppressed adults who switched from a standard boosted protease inhibitor (PI) regimen.

The darunavir-based STR received a Positive Opinion from the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) earlier this month recommending marketing authorization under the brand name of Symtuza� in the European Union.

If approved, it would be the first darunavir-based complete regimen for the treatment of HIV-1 in adults and adolescents (aged 12 years and older with a body weight of at least 40kg, with genotypic testing guiding use), combining the proven efficacy and durability of darunavir with the improved renal laboratory and bone mineral density profile of F/TAF as compared to F/TDF (tenofovir disoproxil fumarate).

"The complexity and high pill burden of some HIV treatment regimens can result in non-adherence, which is one of the major contributors to the development of HIV drug resistance," said Professor Jean-Michel Molina, Professor of Infectious Diseases, Department of Infectious Diseases, St-Louis Hospital, University of Paris Diderot, Paris, France. "These promising results show that the darunavir-based STR was highly effective and well tolerated, providing a complete treatment regimen with a high genetic barrier to resistance with just one single daily tablet. If we can help to reduce the treatment burden for patients living with HIV-1, this can help to improve adherence which we know is essential for achieving viral suppression and reducing the emergence of resistance mutations."

EMERALD is a 48-week, non-inferiority study evaluating the efficacy and safety of switching to D/C/F/TAF (n=763) versus continuing on a boosted PI plus F/TDF regimen (n=378). Cumulative virologic rebound, defined as confirmed viral load (VL) >50c/mL or premature discontinuations, with last VL200c/mL. At Week 24, virologic suppression, defined as VL
Safety was similar between the study arms through 24 weeks with low incidences of Grade 3-4 adverse events (AEs) - 4.5 percent (D/C/F/TAF) and 4.5 percent (control); serious AEs - 2.6 percent (D/C/F/TAF) vs 3.2 percent (control); and treatment discontinuations - overall, 2.9 percent (D/C/F/TAF) vs 2.9 percent (control), and due to AEs, 1.4 percent (D/C/F/TAF) vs 1.1 percent (control). The most common AEs (>5 percent both arms) were nasopharyngitis; upper respiratory tract infection (URI) and vitamin D deficiency. There were no deaths reported during the interim analysis.

"Over the past decade, Janssen has developed a broad range of therapies for people living with HIV that have helped to transform the management of patients living with the disease. Darunavir is one of the most widely used HIV medicines globally and it offers a high genetic barrier to resistance," said Lawrence M. Blatt, Ph.D., Global Therapeutic Area Head, Infectious Disease Therapeutics, Janssen. "We remain dedicated to fulfilling our mission of delivering transformational innovations to meet the diverse needs of the HIV community and are excited to be bringing forward an evolved therapy with darunavir as its backbone. If approved, it has the potential to not only offer the benefits of darunavir but could also reduce the treatment burden faced by those taking life-long HIV therapy, which may help to address the issues of both adherence and resistance."

Additional Darunavir Data at IAS 2017

Two new analyses presented at the conference provide further support for a darunavir-based STR in the treatment of HIV. The first confirmed that the STR is bioequivalent to the combined administration of the separate agents. The bioequivalence study also found the STR was well tolerated. The other poster presentation evaluated the prevalence of darunavir resistance-associated mutations (RAMs) and primary PI resistance from 2010-2015 in clinical samples from the Monogram database and found the prevalence of darunavir RAMs remained low and generally stable.

Treatment regimens that combine DRV/C (REZOLSTA�, Janssen-Cilag International NV, U.S name PREZCOBIX�) and F/TAF (DESCOVY�, Gilead Sciences International Ltd) are currently approved for the treatment of HIV-1.

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