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The European Commission has granted extended approval for the use of ravulizumab-cwvz in young people weighing at least 10 kg, as well as in adolescents with paroxysmal nocturnal haemoglobinuria.
The European Commission has granted extended approval to ravulizumab-cwvz (Ultomiris) for young people weighing at least 10 kg, as well as adolescents with paroxysmal nocturnal haemoglobinuria (PNH). 1
The approval is on the interim effects of a phase 3 trial (NCT03406507), in which the long-acting supplement inhibitor C5 demonstrated efficacy and protection in the paediatric and adolescent patient population (n = 12) with NPH. Specifically, the effects showed that ravulizumab achieves total inhibition of the C5 supplement for 26 weeks in youth and adolescents up to 18 years of age.
In July 2021, the Committee for Medicinal Products for Human Use of the European Medicines Agency extended the indication for ravulizumab on the basis of those data. In June 2021, the FDA granted expanded approval for ravulizumab in the pediatric and adolescent patient population with PNH. .
“NPH is a devastating disease and [ravulizumab] is a breakthrough for paediatric patients in the EU with an established efficacy and protection profile,” said Austin Kulasekararaj, MD, of King’s College Hospital, London, UK. “By requiring fewer infusions per year than [eculizumab], [ravulizumab] would possibly decrease the desire of those young patients to miss school for treatment. “
PNH is a serious and rare blood disease in which the destruction of red blood cells causes thrombosis and causes organ injury and potentially premature death. Ravulizumab first won approval in the European Union in 2019 for the remedy of adult patients with PNH.
The interim effects of the multicenter, single-arm, open-label Phase 3 trial were presented at the 2021 European Hematology Association Congress. 2 Pediatric patients younger than 18 years of age who had not previously received treatment with supplement inhibitors and eculizumab (Soliris) were included. PNH, at nine sites in 6 countries.
Patients who had not previously received treatment with supplement inhibitors were treated with a weight-dependent loading dose of ravulizumab on day 1, followed by a weight-based maintenance dose on day 15, and then once every 8 weeks. day 1. 2 weeks after the last dose of eculizumab.
The number one endpoints of the trial were maximum and minimum serum concentrations of ravulizumab (Cmax, Ctrough), accumulation rate, and replacement in C5 loose concentration. Measures of secondary end-outcomes were lactate dehydrogenase (LDH) replacement rate from baseline, transfusion avoidance (BP), breakthrough hemolysis (BTH), and hemoglobin stabilization (Hgb-S).
Treatment-related adverse events (AAT) and serious adverse events (AAG) were assessed.
In the intermediate investigation (n = 12), four patients had not received any treatment with supplemental inhibitors and 10 (83. 3%) patients were at least 12 years old; median age at the first infusion of ravulizumab 15. 0 years (extremes: 9-17).
Knowledge showed that steady-state healing serum concentrations were reached without delay after the first dose of ravulizumab and remained the number one evaluation period; there was no evidence of accumulation (mean accumulation ratios (SDS) Cmax and Ctrough of 1. 1 [0. 1] and 1. 1 [0. 2], respectively).
In addition, complete terminal inhibition of the supplement is achieved at the end of the first infusion of ravulizumab (defined as the loose mean serum concentration of C5).
The mean percentage of substitution in LDH was –42. 1% (59. 0) in patients without prior treatment with supplement inhibitors; in patients who had gained eculizumab in the past, it remained solid at 4. 65% (44. 7). Ten patients (83. 3%) achieved BP, 8 (66. 7%) Hgb-S and 0 BTH.
In terms of safety, 10 patients had ITI, the non-unusual maximum of which were abdominal pain and nasopharyngitis; however, there has been no meningococcal infection, no death or discontinuation of treatment due to these events. At least 1 AAG occurred in 3 patients, none of whom were related to the remedy.
“This approval of Ultomiris reflects our ongoing commitment to offering new remedies that can make a significant difference in patients’ lives,” said Marc Dunoyer, CEO of Alexion. “Ultomiris has become the popular treatment for the adult remedy with HNP and we will get it as soon as possible to this younger patient population. “
Ravulizumab is given every four to eight weeks, depending on the weight of the structure, after a loading dose.
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