Asfotase Alfa Treatment Improves Survival for Perinatal and Infantile Hypophosphatasia

Whyte, Michael P.; Rockman‐Greenberg, Cheryl; Ozono, Keiichi; Riese, Richard J.; Moseley, Scott; Melian, Agustin; Thompson, David D.; Bishop, Nicholas; Hofmann, Christine

doi:10.1210/jc.2015-3462

Cited by 199 publications

(193 citation statements)

References 33 publications

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“…Impaired hydrolysis of PLP in severely affected babies can lead to neurotransmitter deficiency and vitamin B 6 -dependent seizures (11). The clinical expressivity of hypophosphatasia is classified according to whether there are dental complications alone (odontohypophosphatasia) or to patient age when skeletal and other problems first manifest (1,2,12). Perinatal hypophosphatasia is almost always fatal soon after birth (13), and infantile hypophosphatasia has a mortality estimate of 50% during the first year of life (1,2).…”

Section: Introductionmentioning

confidence: 99%

Asfotase alfa therapy for children with hypophosphatasia

Whyte¹,

Madson²,

Phillips³

et al. 2016

JCI Insight

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Section: Introductionmentioning

confidence: 99%

Asfotase alfa therapy for children with hypophosphatasia

Whyte¹,

Madson²,

Phillips³

et al. 2016

JCI Insight

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129

110

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“…Currently, new pharmacologic treatment includes using enzyme replacement therapy with asfotase alfa to help replace ALP. Recent literature shows asfotase alfa to be effective in treating, decreasing the burden of disease, and improving overall survival of HPP patients [18,19].…”

Section: Discussionmentioning

confidence: 99%

Surgical management for tibial shaft fractures using flexible nailing in adult hypophosphatasia

Bhagat¹,

Sun²,

Rao³

2018

Int J Case Rep Images

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International Journal of Case Reports and Images (IJCRI) is an international, peer reviewed, monthly, open access, online journal, publishing high-quality, articles in all areas of basic medical sciences and clinical specialties.Aim of IJCRI is to encourage the publication of new information by providing a platform for reporting of unique, unusual and rare cases which enhance understanding of disease process, its diagnosis, management and clinico-pathologic correlations. IJCRI publishes Review

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“…Currently, specific medical treatment options for HPP are limited to bone-targeted enzyme replacement therapy (asfotase alfa, Strensiq, Alexion), approved for pediatric-onset HPP (22,37). However, there is only limited evidence demonstrating its efficacy in adults with mild and/or late-onset forms of HPP, and in particular patients with adult onset of the disease are not covered by the label.…”

Section: Discussionmentioning

confidence: 99%

“…with a historical cohort, along with improved skeletal mineralization and significant reductions in the TNSALP substrates PPi and PLP (21,22). However, access to this enzyme replacement therapy is limited by regulatory specifications.…”

Section: Introductionmentioning

confidence: 99%

Efficacy of anti-sclerostin monoclonal antibody BPS804 in adult patients with hypophosphatasia

Seefried

Baumann

Hemsley

et al. 2017

Journal of Clinical Investigation

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BACKGROUND. Hypophosphatasia (HPP) is a rare genetic disorder resulting in variable alterations of bone formation and mineralization that are caused by mutations in the ALPL gene, encoding the tissue-nonspecific alkaline phosphatase (ALP) enzyme. METHODS.In this phase IIA open-label, single-center, intra-patient, dose-escalating study, adult patients with HPP received 3 ascending intravenous doses of 5, 10, and 20 mg/kg BPS804, a fully human anti-sclerostin monoclonal antibody, on days 1, 15, and 29, respectively. Patients were followed for 16 weeks after the last dose. We assessed the pharmacodynamics, pharmacokinetics, preliminary efficacy, and safety of BPS804 administrations at specified intervals during treatment and follow-up. RESULTS.Eight patients (mean age 47.8 years) were enrolled in the study (6 females, 2 males). BPS804 treatment increased mean ALP and bone-specific ALP enzymatic activity between days 2 and 29. Transient increases in the bone formation markers procollagen type-I N-terminal propeptide (PINP), osteocalcin, and parathyroid hormone as well as a transient decrease in the bone resorption marker C-telopeptide of type I collagen (CTX-1) were observed. Lumbar spine bone mineral density showed a mean increase by day 85 and at end of study. Treatment-associated adverse events were mild and transient.CONCLUSION. BPS804 treatment was well tolerated and resulted in increases in bone formation biomarkers and bone mineral density, suggesting that sclerostin inhibition could be applied to enhance bone mineral density, stability, and regeneration in non-life-threatening clinical situations in adults with HPP. TRIAL REGISTRATION. Clinicaltrials.gov NCT01406977. FUNDING.

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Asfotase Alfa Treatment Improves Survival for Perinatal and Infantile Hypophosphatasia

Abstract: Asfotase alfa mineralizes the HPP skeleton, including the ribs, and improves respiratory function and survival in life-threatening perinatal and infantile HPP.

Cited by 199 publications

References 33 publications

Asfotase alfa therapy for children with hypophosphatasia

Asfotase alfa therapy for children with hypophosphatasia

Surgical management for tibial shaft fractures using flexible nailing in adult hypophosphatasia

Efficacy of anti-sclerostin monoclonal antibody BPS804 in adult patients with hypophosphatasia

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