Regulatory Decision Summary for Juluca
The Regulatory Decision Summary explains Health Canada’s decision for the product seeking market authorization. The Regulatory Decision Summary includes the purpose of the submission and the reason for the decision.
Type of submission:
What was the purpose of this submission?
The purpose of the New Drug Submission was to seek market authorization for Juluca, which is indicated as a complete drug regimen to replace the current antiretroviral regimen for the treatment of Human Immunodeficiency Virus 1 (HIV-1) infection in adults who are virologically stable and -suppressed (HIV-1 RNA less than 50 copies per mL).
Why was the decision issued?
Health Canada considers that the benefit/risk profile of Juluca is favourable when used as a complete regimen in the treatment of Human Immunodeficiency Virus 1 (HIV-1) infection in adults who are virologically suppressed (HIV-1 RNA less than 50 copies per mL) and on a stable antiretroviral treatment regimen.
Juluca is a two-drug treatment regimen (fixed dose combination containing dolutegravir and rilpivirine) indicated for use in virologically suppressed HIV-1 infected adults. It is intended to provide a simplified treatment regimen with improved tolerability and offer continued suppression of HIV-1 in individuals who are already virologically-suppressed.
The efficacy, clinical safety and tolerability of Juluca were evaluated in two pivotal, identical, ongoing, randomized, parallel groups, 148 week Phase III studies. The clinical Phase III studies were conducted with the single entities of dolutegravir (DTG) + rilpivirine (RPV). The bioequivalence was established between the single entities and the commercial fixed-dose combination tablet.
The studies assessed the non-inferiority of the antiviral activity of DTG + RPV once daily in subjects who changed from their original treatment regimen to DTG+RPV compared to the patients who remained on their current antiretroviral 3-drug regimen through 48 weeks. The studies also investigated the long-term antiviral activity, tolerability and safety of DTG+RPV through week 148. The primary efficacy endpoint was the proportion of subjects with plasma HIV-1 RNA <50 copies per millilitre (c/mL) at Week 48 using the Snapshot algorithm for the Intent-to-treat exposed population.
The non-inferiority was demonstrated for continued suppression at <50 copies/ml until 48 weeks and for rates of virologic failure through 48 weeks for the 2-drug DTG+RPV fixed dose combination in virologically suppressed patients compared to patients who remained on their current antiretroviral regimen. There were few cases of virologic failure in the DTG+RPV group in either study and no association with virologic resistance to integrase inhibitors or nucleoside reverse transcriptase inhibitors was detected after 48 weeks.
The individual components of Juluca have established safety profiles. The adverse event profiles showed a risk of psychiatric disorders, gastrointestinal and hepatic events in particular. There were no new safety concerns associated with this product.
The risks for a two-drug regimen as compared to standard three drug regimen are virologic failure and the potential for development of resistance. The benefit of a two-drug fixed dose combination is improved adherence, tolerability and quality of life for eligible subjects. Additionally, Juluca does not include any of the nucleoside reverse-transcriptase inhibitor or protease inhibitor classes of drugs (which are both typical components of three-drug regimens), hence these classes are preserved for future use, if considered necessary.
Based on the data submitted, at this time Health Canada considers that the anticipated benefits outweigh the potential risks under the conditions of use as described in the Product Monograph for Juluca.
Approved; issued a Notice of Compliance in accordance with the Food and Drug Regulations.