Abstract
IntroductionLong-term outcome data provide important insights into the clinical utility of enzyme replacement therapies. Such data are presented for velmanase alfa in the treatment of alpha-mannosidosis (AM).MethodsPatient data (n = 33; 14 adults, 19 paediatric) from the clinical development programme for velmanase alfa were integrated in this prospectively-designed analysis of long-term efficacy and safety. Patients who participated in the phase I/II or phase III trials and were continuing to receive treatment after completion of the trials were invited to participate in a comprehensive evaluation visit to assess long-term outcomes. Primary endpoints were changes in serum oligosaccharide and the 3-minute stair climb test (3MSCT).ResultsMean (SD) treatment exposure was 29.3 (15.2) months. Serum oligosaccharide levels were significantly reduced in the overall population at 12 months (mean change: –72.7%, P < 0.001) and remained statistically significant at last observation (−62.8%, P < 0.001). A mean improvement of +9.3% in 3MSCT was observed at 12 months (P = 0.013), which also remained statistically significant at last observation (+13.8%, P = 0.004), with a more pronounced improvement detected in the paediatric subgroup. No treatment-emergent adverse events were reported leading to permanent treatment discontinuation.ConclusionsPatients treated with velmanase alfa experienced improvements in biochemical and functional measures that were maintained for up to 4 years. Long term follow-up is important and further supports the use of velmanase alfa as an effective and well-tolerated treatment for AM. Based on the currently available data set, no baseline characteristic can be predictive of treatment outcome. Early treatment during paediatric age showed better outcome in functional endpoints.
Highlights
Long-term outcome data provide important insights into the clinical utility of enzyme replacement therapies
Individual patient data from phase I/II (Borgwardt et al 2013) and III trials and the subsequent rhLAMAN-07 (NCT01908712), rhLAMAN-09 (NCT01908725) and rhLAMAN-10 (NCT02478840) studies were integrated into a single database. rhLAMAN-07 and rhLAMAN-09 are ongoing clinical trials of once-weekly 1 mg/kg velmanase alfa treatment in patients from France, or from Poland and Norway, respectively, who previously participated in velmanase alfa trials. rhLAMAN-10 is a single-centre clinical trial of 1 mg/kg velmanase alfa in which patients who had previously participated in velmanase alfa clinical trials and subsequently enrolled in the international compassionate use (CU) programme were invited to undergo a comprehensive evaluation visit
Thirty-four patients participated in phase I/II and III trials and received velmanase alfa treatment as part of rhLAMAN-07, −09 or CU programme
Summary
Long-term outcome data provide important insights into the clinical utility of enzyme replacement therapies. Such data are presented for velmanase alfa in the treatment of alpha-mannosidosis (AM). Serum oligosaccharide levels were significantly reduced in the overall population at 12 months (mean change: –72.7%, P < 0.001) and remained statistically significant at last observation (−62.8%, P < 0.001). Velmanase alfa is a recombinant human lysosomal alphamannosidase, developed as intravenous (IV) enzyme replacement therapy (ERT) for AM (Borgwardt et al 2013). In phase I/II trials, velmanase alfa was associated with a sustained decrease in serum oligosaccharides after 18 months of therapy (mean percentage change −89.9%, P < 0.001) and achievement of an average improvement of 39 steps in the 3-minute stair climb test (3MSCT; P = 0.004) (Borgwardt et al 2014b). We present long-term outcomes in patients with AM treated with velmanase alfa
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