AstraZeneca Launches Two Phase 3 Clinical Trials in China for ALXN1850, a Next-Generation Enzyme Replacement Therapy for Hypophosphatasia

▎Edited by the WuXi AppTec content team

Screenshot source:China Drug Clinical Trial Registration and Information Disclosure Platform Official Website

Hypophosphatasia (HPP) is aRare Single-Gene Hereditary DiseasesDisease,Bone Mineralization Disorders and Tooth Loss, Blood and BonesAlkaline Phosphatase (ALP) LevelCharacterized by paradoxical reduction.HPP is mainly composed ofALPLCaused by gene mutations,ALPLLoss-of-function mutations lead to a reduction in tissue-nonspecific alkaline phosphatase (TNSALP), causing the accumulation of its substrate, extracellular pyrophosphate, which inhibits hydroxyapatite formation. Additionally, extracellular pyrophosphate induces the production of osteopontin, further suppressing hydroxyapatite formation. This is the main mechanism responsible for early tooth loss and abnormal skeletal mineralization in patients.

According to the "Guidelines for the Diagnosis and Treatment of Rare Diseases (2019 Edition)",For HPP patients, excessive calcium or vitamin D supplementation may induce or exacerbate hypercalcemia, hypercalciuria, and hyperphosphatemia, while providing no benefit to bone lesions. Specific enzyme replacement therapy is currently the most effective treatment for HPP.

ALXN1850（efzimfotase alfa) is aTissue-nonspecific alkaline phosphatase (TNSALP) enzyme replacement therapy.Compared with AstraZeneca's earlier HPP therapy asfotase alfa, ALXN1850 has a longer half-life, increased enzyme activity, improved bioavailability and in vivo exposure, and an enhanced manufacturing process.

Screenshot source: Reference [2]

AstraZeneca has launched two Phase 3 clinical trials in China, respectively:

• 1) A randomized, double-blind, placebo-controlled, multicenter Phase 3 study, in previously untreatedasfotase alfaTreatment for Pediatric Patients with Hypophosphatasia (2 years to <12 years)Evaluation of the Efficacy and Safety of Subcutaneous Administration of ALXN1850 Compared to Placebo in Subjects, with the Principal Investigator in China being from Beijing Children's Hospital, Capital Medical UniversityDirector Physician Gong Chunxiu；

• 2) A randomized, double-blind, placebo-controlled, multicenter, Phase 3 study to evaluate ALXN1850 inPreviously untreatedasfotase alfaAdolescent (≥12 years to <18 years) and adult subjects with hypophosphatasiaThe efficacy and safety of subcutaneous administration in China, the main investigator in China for this study is Peking Union Medical College Hospital, Chinese Academy of Medical Sciences.Director Physician Xia Weibo。

[2] AstraZeneca Q4. Retrieved February 9, 2023, from https://www.astrazeneca.com/content/dam/az/PDF/2022/fy/Full-year-and-Q4-2022-results-presentation.pdf