Efficacy of anti-sclerostin monoclonal antibody BPS804 in adult patients with hypophosphatasia
Lothar Seefried, … , Uwe Junker, Franz Jakob
Lothar Seefried, … , Uwe Junker, Franz Jakob
Published April 24, 2017
Citation Information: J Clin Invest. 2017;127(6):2148-2158. https://doi.org/10.1172/JCI83731.
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Clinical Research and Public Health Bone biology Clinical trials

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

Abstract

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. Novartis Institutes for BioMedical Research, Basel, Switzerland.

Authors

Lothar Seefried, Jasmin Baumann, Sarah Hemsley, Christine Hofmann, Erdmute Kunstmann, Beate Kiese, Yue Huang, Simon Chivers, Marie-Anne Valentin, Babul Borah, Ronenn Roubenoff, Uwe Junker, Franz Jakob

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Consolidated Standards of Reporting Trials (CONSORT) diagram. A total of...
A total of 9 patients were screened for the study. Only 8 patients were enrolled in the study, as 1 patient did not meet the study entry criteria. Of the 8 patients, 7 completed the study as per the protocol. One patient discontinued the study due to SAEs of angina pectoris and dyspnea. All patients who received the study drug were included in the safety analysis set; patients with evaluable pharmacokinetic (PK) parameter data were included in the PK analysis set; and patients with evaluable pharmacokinetic (PD) parameter data were included in the PD analysis set.