ViiV Healthcare, the global specialist HIV company, majority owned by GlaxoSmithKline, with Pfizer Inc. and Shionogi Limited as shareholders, announced that the European Commission has granted marketing authorisation for Juluca (dolutegravir 50mg/rilpivirine 25mg) for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in adults who are virologically suppressed (HIV-1 RNA <50 copies/mL) on a stable antiretroviral regimen for at least six months with no history of virological failure and no known or suspected resistance to any non-nucleoside reverse transcriptase inhibitor or integrase inhibitor.

Juluca is a 2-drug regimen of dolutegravir (ViiV Healthcare), the most widely prescribed integrase inhibitor worldwide, and rilpivirine (Janssen Sciences Ireland UC, part of the Janssen Pharmaceutical Companies of Johnson & Johnson).

Deborah Waterhouse, CEO ViiV Healthcare said, “The European Commission Decision for Juluca is very positive news for people living with HIV (PLHIV) across Europe, who will now have the opportunity to maintain their viral suppression with a complete treatment regimen composed of only two drugs within a single-pill. Thanks to advances in treatment, many PLHIV who are on therapy are living longer, with near-normal life expectancies. We listened to their concerns about the potential long-term effects of being on treatment for decades, and have developed a solution aligned with a preference to streamline care by taking fewer antiretrovirals to manage their HIV.”  

This approval brings another treatment option to the estimated 810,000 PLHIV in Europe. It follows the Positive Opinion from the European Medicines Agency’s (EMA) Committee for Human use of Medicinal Products (CHMP) on 22 March 2018. Juluca was approved by the US Food and Drug Administration (FDA) in November 2017 and Health Canada on 18 May 2018.

John C Pottage, Jr, MD, chief scientific and medical officer, ViiV Healthcare, commented, “We are delighted to be able to provide dolutegravir with rilpivirine in a once-daily 2-drug regimen for PLHIV. ViiV Healthcare is committed to delivering innovative advances to meet the unmet needs of PLHIV and our robust clinical research programme has the potential to revolutionalise how we care for PLHIV for the long-term. With the advent of Juluca, we have found a way to reduce the number of antiretrovirals whilst maintaining the efficacy of the traditional 3-drug regimen. This is already being recognised by the European AIDS Society (EACS 2017) guidelines recommending a dolutegravir and rilpivirine regimen as a switch option for virologically suppressed patients.”

Data from the SWORD studies, presented at the Conference for Retroviruses and Opportunistic Infections (CROI) 2017 and later published in The Lancet, showed that the dolutegravir and rilpivirine regimen is non-inferior to traditional three and four drug regimens in maintaining virologic suppression (HIV-1 RNA <50 copies/mL) through 48 weeks in adults who are infected with HIV-1, in both pooled and individual analyses of the SWORD-1 and SWORD-2 studies (dolutegravir+rilpivirine 486/513 [95%] current antiretroviral regimen 485/511 [95%], [adjusted difference -0.2% (95% confidence interval: -3.0%, 2.5%), pooled analysis]). The most commonly reported (>5%) adverse events in the dolutegravir+rilpivirine arm were nasopharyngitis, headache, diarrhoea and upper respiratory tract infection. Participating adults had stable plasma HIV-1 RNA (viral load <50 copies/mL) for 6 months or longer at screening, with no resistance-associated major integrase inhibitor, protease inhibitor, nucleoside and non-nucleoside reverse transcriptase inhibitor mutations.

In June 2014, ViiV Healthcare and Janssen Sciences Ireland UC, one of the Janssen Pharmaceutical Companies of Johnson & Johnson, announced a collaboration to investigate the potential of combining dolutegravir and rilpivirine in a single tablet in order to expand the treatment options available to people living with HIV.

Juluca was approved by the US Food and Drug Administration (FDA) on 21 November 2017, as a complete regimen for the treatment of HIV-1 infection in adults who are virologically suppressed (HIV-1 RNA less than 50 copies per mL) on a stable antiretroviral regimen for at least 6 months with no history of treatment failure and no known substitutions associated with resistance to the individual components of dolutegravir/rilpivirine.

Juluca is a 2-drug regimen, single pill that combines the integrase inhibitor (INI) dolutegravir (50mg), with the non-nucleoside reverse transcriptase inhibitor (NNRTI) rilpivirine (25mg) taken once-daily as a complete HIV regimen for people living with HIV who are virologically suppressed.

Two essential steps in the HIV life cycle include reverse transcription – when the virus turns its RNA (ribonucleic acid) copy into DNA (deoxyribonucleic acid) – and integration – the moment when viral DNA becomes part of the host cell’s DNA. These processes require two enzymes called nucleoside reverse transcriptase and integrase. NNRTIs and INIs interfere with the action of these two enzymes to prevent the virus from replicating. This decrease in replication can lead to less virus being available to cause subsequent infection of uninfected cells.

ViiV Healthcare has also submitted regulatory marketing applications in other countries worldwide.

The SWORD phase III programme evaluates the efficacy, safety, and tolerability of switching to dolutegravir plus rilpivirine from current integrase inhibitor-, non-nucleoside reverse transcriptase inhibitor-, or boosted protease inhibitor-based antiretroviral regimen in HIV-1-infected adults who are virologically suppressed with a three or four-drug regimen. SWORD-1 (NCT02429791) and SWORD-2 (NCT02422797) are replicate 148-week, randomised, open-label, non-inferiority studies to assess the antiviral activity and safety of a two-drug, daily oral regimen of dolutegravir plus rilpivirine compared with current antiretroviral therapy (100-week data will be shared in Q3 2018 with the full 148-week data being shared in 2019). In the SWORD clinical trials, dolutegravir and rilpivirine are provided as individual tablets.

The primary endpoint is the proportion of patients with plasma HIV-1 RNA <50 copies per millilitre (c/mL) at week 48. Key secondary endpoints include evaluation of the development of viral resistance, measurements of safety and tolerability, and changes in renal, bone and cardiovascular biomarkers. The studies also include exploratory measures to assess change in health-related quality of life, willingness to switch and adherence to treatment regimens.