AstraZeneca's Novel Enzyme Replacement Therapy ALXN1850 Granted Clinical Trial Approval in China for Hypophosphatasia

Feb 20, 2024 08:01 CST Updated 08:01

AstraZeneca

Biopharmaceutical Manufacturer

Alexion

Developer of New Drugs for Rare Disease Treatment

▎WuXi AppTec Content Team Report

On February 19, the official website of the Center for Drug Evaluation (CDE) of the China National Medical Products Administration (NMPA) announced,Alexion, AstraZeneca Rare Disease, a unit of AstraZeneca focused on rare diseasesAlexion's Class 1 new drug ALXN1850 Injection has received implied permission for clinical trials and is proposed for development.As enzyme replacement therapy for the treatment ofHypophosphatasia (HPP). According to publicly available information from AstraZeneca, thisIs a new generation under developmentTissue Non-Specific Alkaline Phosphatase Enzyme Replacement Therapy (ERT), and several Phase 3 clinical trials for the treatment of HPP are currently being conducted internationally.

Screenshot source:CDE Official Website

Hypophosphatasia (HPP) is aRare Monogenic Hereditary DiseaseDisease,Bone mineralization disorders, tooth loss, blood and boneAlkaline Phosphatase (ALP) LevelCharacterized by paradoxical reduction.HPP is mainly composed ofALPLCaused by gene mutations,ALPLInactivating gene 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 primary 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 patients with HPP, excessive supplementation of calcium or vitamin D may induce or exacerbate hypercalcemia, hypercalciuria, and hyperphosphatemia, without benefiting their skeletal disorders. 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 systemic exposure, and an enhanced manufacturing process.

Screenshot source: Reference [2]

According toClinicalTrialsAccording to the official website, Alexion is currently conducting three projects in the United States, Australia, and other places.The international multi-center Phase 3 clinical study of ALXN1850, respectively targetingPreviously untreated with asfotase alfaAdolescent and Adult HPP Patients, previously treated with asfotase alfa and untreatedChildren with HPP(2~12 years old).ThisALXN1850 Approved for Clinical Trials in China, Indicating the Product is Set to Begin Clinical Research for HPP Treatment in China.

References:

[1] Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) of China. Retrieved Feb 18, 2024, from https://www.cde.org.cn/main/xxgk/listpage/4b5255eb0a84820cef4ca3e8b6bbe20c

[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

[3]Alexion Official Website. Fromhttps://alexion.com/our-research/pipeline

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