Type of information: Positive opinion for the granting of a Market Authorisation in the EU
Product name: Juluca® (dolutegravir and rilpivirine)
Compound: dolutegravir and rilpivirine
Therapeutic area: Infectious diseases
- integrase inhibitor/non-nucleoside reverse transcriptase inhibitor. Dolutegravir is an investigational integrase inhibitor (INI). Integrase inhibitors block HIV replication by preventing the viral DNA from integrating into the genetic material of human immune cells (T-cells). This step is essential in the HIV replication cycle and is also responsible for establishing chronic infection. Given the stage of development of this investigational HIV therapy, the full picture of the efficacy and safety of dolutegravir has not been conclusively determined.
- Rilpivirine (Edurant®) is a non-nucleoside reverse transcriptase inhibitor.
- In June 2014, ViiV Healthcare UK and Janssen Sciences Ireland , announced a collaboration to investigate the potential of combining dolutegravir and rilpivirine in a single-pill in order to expand the treatment options available to people living with HIV.
Company: ViiV Healthcare (UK - USA)
Disease: maintenance treatment of HIV-1 infection
- On March 22, 2017, the Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion, recommending the granting of a marketing authorisation for Juluca®, intended for the treatment of HIV infection. Juluca® will be available as 50 mg/25 mg film-coated tablets. The benefit with this drug is its ability to maintain viral suppression of HIV strains that lack resistance
(documented or clinically suspected) to integrase inhibitors. The most common side effects are insomnia, headache, dizziness, nausea and diarrhoea.
- The full indication is: "Juluca is indicated for the treatment of human immunodeficiency virus type 1 (HIV1) 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. It is proposed that Juluca be prescribed by physicians experienced in the management of HIV infection.
- Data from the SWORD-1 and SWORD-2 trials was recently published in The Lancet (5 January, 2018) and showed that the dolutegravir and rilpivirine regimen is non-inferior to three- and four-drug regimens in maintaining virologic suppression (HIV-1 RNA <50 c/mL) through 48 weeks in adults who are infected with HIV-1 and have no resistance, in both pooled and individual analyses of these Phase 3 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]). Virologic suppression rates were similar between treatment arms.
- • On November 21, 2017, the FDA has approved Juluca®, indicated as a complete regimen for the maintenance treatment of HIV-1 infection in adults who are virologically suppressed (HIV-1 RNA less than 50 copies per mL) on a stable antiretroviral (ART) regimen for at least six months with no history of treatment failure and no known substitutions associated with resistance to the individual components of Juluca. The approval is based primarily upon data from two pivotal phase III clinical trials, SWORD-12 and SWORD-2,2 which showed the 2-drug regimen achieved non-inferior viral suppression (HIV-1 RNA less than 50 copies per mL) at 48 weeks compared with a three- or four-drug regimen in both pooled and individual analyses of the SWORD-1 and SWORD-2 studies (CAR 485/511 [95%], dolutegravir + rilpivirine 486/513 [95%] [adjusted difference -0.2% (95% confidence interval CI: 3.0%, 2.5%), pooled analysis]).2 Virologic suppression rates were similar between treatment arms.2 Drug related adverse events and adverse events leading to withdrawal occurred in low frequencies in both arms of the study, but more frequently in the investigational arm.
- • On June 1, 2017, ViiV Healthcare, the global specialist HIV company majority-owned by GSK, with Pfizer and Shionogi, announced regulatory submissions to the European Medicines Agency (EMA) and FDA for a single-tablet, two-drug regimen of dolutegravir (Tivicay, ViiV Healthcare) and rilpivirine (Edurant, Janssen Sciences Ireland UC) for the maintenance treatment of HIV-1 infection. The submissions are based on the SWORD studies that included more than one thousand patients who previously achieved viral suppression on a three- or four-drug (integrase inhibitor, non-nucleoside reverse transcriptase inhibitor, or protease inhibitor-based) antiretroviral regimen. This 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. 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 results of these studies were presented at the 2017 Conference on Retroviruses and Opportunistic Infections (CROI) in February.
- A recently acquired priority review voucher was submitted to the FDA along with the dolutegravir and rilpivirine 2-drug regimen New Drug Application (NDA). Under the Prescription Drug User Fee Act, the anticipated target action date is six months after receipt of the application by the FDA. The $130 million cost of the voucher will be reported as an R&D expense in GSK’s Q2 2017 Adjusted results.
Submission of marketing authorization application USA : 2017-06-01
Submission of marketing authorization application UE: 2017-06-01
Withdrawal of marketing authorization application USA:
Withdrawal of marketing authorization application UE:
US authorization: 2017-11-21
Favourable opinion UE: 2018-03-22
Favourable opinion USA:
Orphan status USA:
Orphan status UE:
Pediatric exclusivit _USA:
Pediatric exclusivity UE: