Analysis of the success and failure of non-hormonal drug therapy development for menopausal hot flashes
10.13699/j.cnki.1001-6821.2024.16.025
- VernacularTitle:更年期潮热非激素药物疗法的研发成败案例分析
- Author:
Yu-Xi XIANG
1
;
Xia CHEN
Author Information
1. 中国药科大学基础医学与临床药学学院,江苏南京 211198
- Keywords:
desvenlafaxine extended-release tablet;
esmirtazapine tablet;
paroxetine capsule;
menopausal hot flashes;
case study
- From:
The Chinese Journal of Clinical Pharmacology
2024;40(16):2418-2423
- CountryChina
- Language:Chinese
-
Abstract:
This article provides an in-depth analysis of the clinical development process of three non-hormonal drugs,desvenlafaxine extended-release tablets,esmirtazapine tablets and paroxetine capsules,for the treatment of menopausal hot flashes.Both desvenlafaxine extended-release tablets and esmirtazapine tablets were rejected by regulators for poor benefit-risk balance due to inadequate efficacy and safety concerns.In contrast,paroxetine capsules effectively reduced the risk of drug development failure by setting placebo lead-in periods,more conservative sample size estimates,and pre-specifying meta-analyses of key efficacy measures in the two phase Ⅲ trials,not only demonstrating efficacy in the frequency and degree of hot flashes,but also exploring the best-tolerated dose through multiple phase Ⅱ trials,which was finally approved by the U.S.Food and Drug Administration.The development of non-hormonal drugs for the treatment of menopausal hot flashes faces many challenges,including drug safety characteristics that are different from those in patients with psychiatric diseases,weak drug efficacy,weak correlation between preclinical efficacy models and clinical symptom remission,and the need for large sample sizes for dose-finding trials.This case study provides a strategic reference for optimizing trial design and reducing the risk of drug development for subsequent drug development with similar indications.
