Sanofi's Aubagio (Teriflunomide) Receives EU Approval as First Oral First-Line Therapy for Pediatric Relapsing-Remitting Multiple Sclerosis
Jun 19, 2021 04:52
CST Updated
04:52
Sanofi
Pharmaceutical R&D Developer
Multiple Sclerosis (MS, image source: medgadget.com)
June 18, 2021 /BioonBIOON/ -- Sanofi recently announced that the European Commission (EC) has approved an expanded indication for Aubagio (teriflunomide) for the first-line treatment of pediatric patients aged 10 to 17 years with relapsing-remitting multiple sclerosis (RRMS). Notably,Aubagio is the first oral MS therapy approved in the EU for the first-line treatment of multiple sclerosis (MS) in children and adolescents.The approval of this pediatric indication provides Aubagio with an additional year of market protection in the European Union.
Aubagio received marketing approval in the United States in September 2012 and in the European Union in August 2013 for the treatment of adult patients with relapsing-remitting multiple sclerosis (RRMS). As an industry-leading oral MS therapy, it has been launched in over 80 countries and regions worldwide.In China, Aubagio (Chinese trade name: Aobajie) received marketing approval in July 2018, becoming the first oral disease-modifying therapy (DMT) approved in China for the treatment of MS.
It is estimated that MS affects approximately 2.8 million people worldwide, with children and adolescents accounting for at least 30,000. Pediatric MS is a rare disease, with 98% of pediatric patients experiencing a relapsing-remitting disease course. Compared with adult-onset MS, pediatric patients typically present with a higher relapse rate and a greater lesion burden. Due to the earlier age of onset, irreversible disability and secondary progression generally occur at a younger age compared to adults. The symptoms of MS impact all aspects of children’s and adolescents’ lives, ranging from physical health to social development and self-esteem.
Erik Wallstrom, Head of Neurology Development at Sanofi Genzyme, said: “Pediatric MS remains an area of significant unmet medical need. The European Commission’s approval of Aubagio for pediatric patients means that children and adolescents with MS in Europe now have a new treatment option, and more importantly, this option can deliver meaningful improvements in the treatment of this serious disease.”
Efficacy and Safety of Aubagio in Pediatric Patients:
The Phase 3 TERIKIDS study (NCT02201108) is a multicenter, randomized, double-blind, placebo-controlled, parallel-group trial that enrolled 166 pediatric patients with relapsing-remitting multiple sclerosis (RRMS) from 22 countries. The study comprised a screening period (up to 4 weeks), followed by a double-blind treatment period (treatment for up to 96 weeks post-randomization). A 96-week open-label extension period is ongoing. The primary endpoint was the time to first confirmed clinical relapse, with pre-specified sensitivity analyses including high magnetic resonance imaging (MRI) activity as a relapse equivalent. Additionally, patients who completed the double-blind period or exhibited high MRI activity were eligible to continue into the open-label extension period.
In this study, 109 patients were randomized to the Aubagio group and 57 patients to the placebo group. During the double-blind treatment period, patients who experienced a clinical relapse or demonstrated high MRI activity were switched to open-label Aubagio treatment. Primary efficacy outcomes and safety and tolerability data from the double-blind core study period (96 weeks post-randomization) were presented online at the 2020 EAN...Conferencepublished on. Results showed:
— Regarding the primary endpoint,Numerically, the Aubagio group demonstrated a 34% reduction in the risk of clinical relapse compared with the placebo group., but did not reach statistical significance.The time to first confirmed clinical relapse was delayed in the Aubagio group compared with the placebo group (median time: 75.3 weeks vs 39.1 weeks; HR = 0.66; 95% CI: 0.39-1.1; p = 0.29). Due to high MRI activity, conversion from double-blind to open-label treatment occurred more frequently than expected. Compared with the Aubagio group, the placebo group exhibited a higher and earlier conversion rate (26% vs. 14%, respectively). This reduced the statistical power of the study for the primary endpoint.
In a prespecified sensitivity analysis of the composite endpoint of time to first disease activity (time to first confirmed clinical relapse or time to highly active MRI meeting study criteria for switching to open-label treatment),Compared with placebo, Aubagio reduced the risk of first confirmed clinical relapse or conversion to open-label treatment due to high MRI activity by 43% and delayed the time to event (median time: 72.1 weeks vs 37.0 weeks)；HR=0.57；95%CI:0.37-0.87；p=0.04）。
— Regarding the key secondary endpoints,Compared with placebo, Aubagio significantly reduced the number of gadolinium-enhancing (Gd+T1) lesions on MRI scans by 75% (p<0.0001) and the number of new or enlarging T2 lesions by 55% (p=0.0006).
In this study, Aubagio was well tolerated with a manageable safety profile in the pediatric population. The overall incidence rates of adverse events (AEs) and serious adverse events (SAEs) were similar between the Aubagio and placebo groups (88.1% vs. 82.5%, and 11.0% vs. 10.5%, respectively), and no deaths occurred during the study. AEs with a higher incidence in the Aubagio group compared to the placebo group (difference ≥5%) included nasopharyngitis, upper respiratory tract infection, alopecia, paresthesia, abdominal pain, and elevated blood creatine phosphokinase (≥3 times the upper limit of normal). During the double-blind period, pancreatitis occurred in 1.8% (2/109) of patients treated with Aubagio, whereas none were reported in the placebo group. During the open-label period of the study, two additional cases of pancreatitis and one case of severe acute pancreatitis (with pseudopapillary tumor) were reported in patients receiving Aubagio. (Bioon.com)