辉瑞：PDE4湿疹药物Crisaborole,获婴儿适应症
1.2016年5月，辉瑞以52亿美元巨资收购Anacor，旨在获得其非甾抗炎PDE4（磷酸二酯酶4）抑制剂新药Crisaborole（克立硼罗，商品名Eucrisa）。2016年12月14日，美国FDA批准2%克立硼罗乳膏用于两岁以上患者中治疗轻度至中度特应性皮炎（ Atopic Dermatitis）（或称为湿疹，eczema）。
Crisaborole结构式
2.当时，辉瑞对Crisaborole的商业前景十分看好，预计年销售峰值将超过20亿美元。基于数量庞大的轻度至中度特应性皮炎/湿疹患者群体缺少安全有效的局部治疗药物，本领域存在着显着未获满足的巨大医疗需求。特应性皮炎/湿疹是一种常见的复发慢性炎性皮肤疾病，患者通常表现为以炎症和瘙痒为特点的慢性皮疹，好发于皮肤褶皱处，症状通常会持续14天以上。据估计，在美国大约有2500万人受特应性皮炎（湿疹）困扰，其中婴儿和儿童占8%~18%。
临床试验时，湿疹患者用药前后真实对比图，需要说明的是可能有个体差异。
3.2017年，Crisaborole（克立硼罗，商品名Eucrisa）销售额6700万美元；2018年，Crisaborole全球销售额为1.47亿美元；2019年，Crisaborole全球销售额同比下滑了7%，为1.38亿美元；2019前3季度仅9200万美元，同比下滑12%；目前除美国外，获批的国家还有加拿大、澳大利亚、以色列。销售额几乎来自于美国。
4.主要由于Crisaborole销售业绩大大低于预期，辉瑞2019年Q4约有27亿美元的资产减值损失。本靶点外用新药开发企业不算拥挤，可能由于看到了前方的失败。
IL-4Rα抗体Dupixent（Dupilumab），2019财年销售同比增长151%达到23.16亿美元，目前获批适应症有中度至重度特应性皮炎、哮喘和鼻窦炎伴鼻息肉，多个适应症处于后期临床阶段。本品最早于2017年3月获批。
5.此前在2019年7月1日，辉瑞公布Crisaborole（克立硼罗，商品名Eucrisa）用于治疗137名3个月~24个月大的轻度至中度特应性皮炎患儿的Ⅳ期临床试验（CrisADe CARE 1）的积极结果，连续用药4周具有良好的安全性特征，与先前的临床经验一致。
6.2020年3月24日，Crisaborole的用于3～24个月轻度至中度特应性皮炎婴幼儿患者适应症(sNDA)获批。3个月以下的婴儿适应症还未获批。
7.Crisaborole（克立硼罗）化合物专利为WO2006089067A2；中国化合物专利CN101914109B于2026年2月16日到期；美国于2026年6月专利到期。
8.2020年2月10日，CDE受理承办公示了辉瑞提交的克立硼罗软膏上市申请（受理号：JXHS2000008）。此前，Crisaborole（克立硼罗)被CDE纳入2019年5月发布的第二批临床急需境外新药名单。中国商品名为舒坦明®。
沛儿13价肺炎疫苗2019年销售额58.47亿美元 ；CDK4/6抑制剂哌柏西利2019年销售额49.61亿美元；JAK抑制剂托法替布，2019年销售额22.42亿美元；另外辉瑞生物类似药已成为公司重要业务单元之一，2019财年业绩达9.11亿美元，主要来自Inflectra/Remsima、 Retacrit驱动。
由生物制药小编制图
更全资料，发送辉瑞至药融圈微信公众号（扫描下二维码）后台可获得辉瑞2019年业绩报告原PDF文件。仅供学习交流分享！
附，获批新闻原文：
Tuesday, March 24, 2020 - 6:45am
Pfizer Inc. (NYSE: PFE) announced today that the U.S. Food and Drug Administration (FDA) has approved its supplemental New Drug Application (sNDA) for EUCRISA® (crisaborole) ointment, 2%, extending the lower age limit from 24 months down to 3 months in children with mild-to-moderate atopic dermatitis (AD), also known as eczema.1 EUCRISA was previously approved for use in adults and children 2 years of age and older.2 This supplemental approval makes EUCRISA the first and only steroid-free, topical prescription medication for mild-to-moderate AD patients as young as 3 months of age.
"Families often spend hours each day attempting to ease their child’s eczema symptoms, affecting both infants and caregivers. This is a struggle I see in my daily practice, and it can take a toll on the entire family," said Lawrence Eichenfield, M.D., chief of Pediatric and Adolescent Dermatology at Rady Children's Hospital-San Diego, vice chair of the Department of Dermatology, and a professor of Dermatology and Pediatrics at UC San Diego School of Medicine. "The approval of a steroid-free treatment option for this age group offers potential relief for these very young patients."
AD is a chronic skin disease characterized by inflammation of the skin and skin barrier defects that affects nearly 18 million people and approximately 11% of children in the U.S.3,4,5 Early onset AD is the most common form of the condition and begins within the first two years of life.6 A total of 45% of all AD cases begin within the first six months of life, and 60% begin during the first year.4,7
“Despite atopic dermatitis often manifesting during infancy, there are few approved treatment options for this population available today,” said Richard Blackburn, Global President, Inflammation & Immunology, Pfizer. “We are committed to making a meaningful difference to patients’ lives, and with this indication extension, we look forward to now helping many of the youngest children suffering with eczema.”
The approval for the expanded indication of EUCRISA was supported by
data from a Phase 4, open-label, clinical study designed to assess the
safety of crisaborole ointment in infants aged 3 months to less than 24
months with mild-to-moderate AD, with effectiveness as an exploratory
endpoint. In this study, crisaborole ointment, 2%, was well-tolerated
and demonstrated effectiveness in patients with mild-to-moderate AD with
no new safety signals identified.8
About the CrisADe CARE 1 Study
The sNDA submission was based on data from the Phase 4 CrisADe CARE 1 trial. The four-week, multicenter, open-label, single-arm study evaluated the safety of crisaborole ointment, 2%, applied twice daily in 137 pediatric patients who were 3 months to less than 24 months of age, with effectiveness as an exploratory endpoint. All patients had mild-to-moderate AD involving at least 5% treatable body surface area (%BSA), excluding the scalp. A cohort of 21 of the 137 subjects was included in a subgroup for pharmacokinetic (PK) assessment, with clinical diagnoses of moderate AD and a minimum of 35% treatable %BSA, excluding the scalp.8
Additional information about the study can be found at www.clinicaltrials.gov.
参考：
NMPA/CDE；
药融圈数据；
FDA/EMA；
相关公司公开披露；
https://s21.q4cdn.com/317678438/files/doc_financials/Quarterly/2019/q4/Q4-2019-PFE-Earnings-Release.pdf；
https://s21.q4cdn.com/317678438/files/doc_financials/2019/q4/Q4-2019-Earnings-Charts-FINAL.pdf；辉瑞2019业绩；
https://s21.q4cdn.com/317678438/files/PFE-USQ_Transcript_2020-01-28.pdf；辉瑞2019财报电话会纪要；
https://investors.pfizer.com/investor-news/press-release-details/2020/PFIZER-REPORTS-FOURTH-QUARTER-AND-FULL-YEAR-2019-RESULTS/default.aspx；
http://www.pharmatimes.com/news/pfizer_completes_$5.2bn_acquisition_of_anacor_1049226；
https://www.fda.gov/news-events/press-announcements/fda-approves-eucrisa-eczema?source=govdelivery&utm;_medium=email&utm;_source=govdelivery；
https://www.eucrisa.com/；
http://labeling.pfizer.com/ShowLabeling.aspx?id=5331；说明书等等。
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