Bone Abstracts

Objectives: Hypophosphatasia (HPP) is a rare metabolic disease caused by loss-of-function mutation(s) in the gene encoding tissue-nonspecific alkaline phosphatase (TNSALP). HPP in infants is characterized by poor skeletal mineralization, respiratory compromise, and a high risk of mortality. We previously reported improved mineralization and respiratory function in 15 patients enrolled in this second study of asfotase alfa, a bone-targeted recombinant human TNSALP, in infants and young children.¹ Here we update this information with data from longer follow-up (≤120 weeks) and additional patients (total n=28).

Methods: Study ENB-010-10 is an ongoing multinational, Phase II, open-label trial of asfotase alfa (SC, 6 mg/kg per week; adjustments permitted) in patients ≤5 years old with HPP onset <6 months. The primary endpoint is change in bone manifestations of HPP at Week 24 (data imputation applied), assessed using a 7-point Radiographic Global Impression of Change (RGI-C) scale (−3=severe worsening; +3=complete healing). Other evaluations include respiratory status and safety. Data are reported as median (min, max).

Results: Twenty-eight patients (57% female, age 66.9 (0.1, 309.9) weeks) were included in this interim analysis: 27 and 15 patients were treated ≥3 and ≥12 months, respectively (duration: 393 (3, 1199) days); one patient withdrew (encephalopathy considered unrelated to treatment). Two patients died (respiratory compromise considered unrelated to treatment). RGI-C score improved with +1.7 (−1.7,+3.0; P<0.0001; n=28) at 24 weeks, +2.0 (0,+3.0; P<0.0001; n=19) at 48 weeks, and +2.5 (+1.7,+3.0; P=0.002; n=10) at 120 weeks of treatment. Twelve (43%) patients did not require respiratory support at any time. Of 16 patients who required support (12 at baseline): five no longer required support and three improved their respiratory status at last assessment. The most common treatment-related adverse events were mild-to-moderate injection-site reactions (180 events/15 patients). Three serious adverse events were considered possibly related to treatment (injection-associated chills and pyrexia: one patient; pneumonia: one patient).

Conclusions: Infants and young children with HPP treated with asfotase alfa experienced improvement in bone manifestations and respiratory function, sustained through up to 120 weeks of treatment. This study further supports the efficacy and safety of asfotase alfa in this population.

References

1. Rockman-Greenberg Horm Res Paediatr 2013 80 (Suppl 1)

Disclosure:: Tatjana Odrljin and Scott Moseley are employees of Alexion Pharmaceuticals Inc, which sponsored the study.

Christine Hofmann is a Study investigator. She has received research support, grants, and consulting fees from Alexion Pharmaceuticals Inc.

Cheryl Rockman-Greenberg is clinical trials site investigator. She has received honoraria and travel support from Alexion Pharmaceuticals, Inc.

Paul Harmatz is a Study investigator. He has received consulting fees from Alexion Pharmaceuticals, Inc.

Johannes Liese is a Study investigator. He has received study grants from Alexion Pharmaceuticals, Inc.