In late November, the FDA approved ViiV Healthcare’s Juluca (dolutegravir + rilpivirine) for the treatment of adults infected with human immunodeficiency virus (HIV), specifically as a maintenance therapy for those with virologically suppressed HIV-1 infections. Not only is Juluca the first two-drug regimen to be approved for the treatment of HIV, but it is also the first nucleoside reverse transcriptase inhibitor (NRTI)-free regimen to receive licensure—both of which are distinctions that GlobalData anticipates will allow the product to establish a solid position in a niche population in the increasingly competitive HIV marketplace.
Juluca’s approval was based on the fact that it demonstrated non-inferior viral suppression (HIV-1 RNA <50copies/mL) at 48 weeks compared to three- and four-drug regimens in two pivotal Phase III studies (SWORD-1 and SWORD-2). Drug-related adverse events (AEs) occurred with equally low frequency across all treatment arms from both studies, and importantly, treatment-emergent resistance—specifically resistance to dolutegravir—was not reported. The absence of treatment-associated resistance across both trials is noteworthy, as all previously approved antiretroviral therapies (ARTs) included at least three drugs, two of which were NRTIs, in order to suppress viral resistance.
ViiV is driving the development of two-drug combination therapies with two further products in development, cabotegravir + rilpivirine and dolutegravir + lamivudine. As current ART regimens contain at least three drugs, including a backbone of two NRTIs, this causes an increased risk of AEs associated with cumulative ART exposure, particularly renal- and bone-related issues. Drug toxicity creates a burden for HIV patients receiving these drugs, resulting in lower compliance to treatment and increased risk of HIV transmission.
GlobalData also identifies long-acting treatments as a major unmet need in HIV care, as they would address compliance issues in certain patients. GlaxoSmithKline (GSK), the majority stakeholder in ViiV, is now turning its focus to the development of its two-drug, long-acting HIV treatment with the announcement of another Phase III trial, investigating a two-month dosing regimen. This long-acting combination therapy consisting of cabotegravir + rilpivirine is currently being investigated in two Phase III trials with a monthly dosing regimen.
Although Phase III results are yet to be published, if cabotegravir + rilpivirine is shown to be effective with administration every two months, it will massively improve the uptake of the product. As such, ViiV’s range of two-drug therapies currently looks promising. GlobalData expects Juluca’s annual sales to exceed $2B by 2025.
Nevertheless, stiff competition is expected in the HIV space, with Gilead’s bictegravir + emtricitabine + tenofovir alafenamide (BIC/FTC/TAF) looking set for approval in 2018. Gilead’s combination therapy targets treatment-naïve patients and therefore has the potential to undercut Juluca by treating new patients, in addition to obtaining patient switching from Gilead’s other TAF-containing, single-tablet regimens (STRs). As market positioning holds such high stakes in a crowded space, both Juluca and BIC/FTC/TAF submitted Priority Review vouchers with their New Drug Applications, positioning these products for a showdown in 2018.