Bone Abstracts (2014) 3 PP363 | DOI: 10.1530/boneabs.3.PP363

Sustained efficacy and tolerability in infants and young children with life-threatening hypophosphatasia treated with asfotase alfa

Michael Whyte1, Jill Simmons2, Richard Lutz3, Marc Vallée4, Agustin Melian5, Tatjana Odrljin4 & Nick Bishop6,7


1Shriner’s Hospital for Children, St Louis, Missouri, USA; 2School of Medicine, Vanderbilt University Nashville, Tennessee, USA; 3University of Nebraska Medical Center, Omaha, Nebraska, USA; 4Alexion Pharmaceuticals, Cambridge, Massachusetts, USA; 5Alexion Pharmaceuticals, Cheshire, Connecticut, USA; 6Sheffield Children’s Hospital, Sheffield, UK; 7University of Sheffield, Sheffield, UK.


Background: Hypophosphatasia (HPP) results from inactivating mutation(s) in the gene for tissue non-specific alkaline phosphatase (TNSALP). Substantial improvement has been reported in skeletal mineralization and physical function in patients (pts) with life-threatening perinatal and infantile HPP treated for 48 weaks with asfotase alfa, a bone-targeted recombinant human TNSALP.

Objective: To evaluate long-term efficacy and tolerability of asfotase alfa in these pts.

Design/methods: Continued assessment using a Radiographic Global Impression of Change (RGI-C) scale (−3=severe worsening; +3=complete healing), Rickets Severity Scale (RSS; 0–10, 10=severe) and respiratory status during asfotase alfa treatment (Rx; s.c. injection, 3x/week, 1–3 mg/kg) for ≥3 years.

Results: The study enrolled 11 points (median age 6.8 months; range 2.9 weeks-3 years). One point withdrew after first Rx and one point died at Rx 7.9 mo (sepsis unrelated to Rx). Median Rx duration was 35 months (n=11, range 1 day-49 months). Asfotase alfa was well tolerated; the most common adverse events (AEs) were mild/moderate injection-site reactions and upper respiratory tract infection (six points each). Three serious AEs were reported as possibly Rx-related; craniosynostosis (a known complication of HPP), conductive deafness and chronic hepatitis. Median RGI-C (+2.50, range: 1.67–3.0; P=0.008) and median change from baseline in RSS (−6.25, range −9.5 to 0.0; P=0.016) showed sustained improvement from baseline at 3 years of Rx (n=8, one pt missing data at 3 years). Ten pts (including the two who died or withdrew) required respiratory support at some time during the first 48 weeks, after which three points remained on respiratory support. Subsequently two discontinued support and one improved to supplemental oxygen at last assessment (≥3 years). Probability of survival at 3 years of Rx was 90%.

Conclusion: Infants and young children with life-threatening HPP treated with asfotase alfa show sustained improvement in skeletal mineralization and respiratory status for ≥3 years.

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