2018年3月23日,Nobelpharma Co.Ltd宣布，孤儿药Rapalimus（Sirolimus，ラパリムスゲル0.2%，西罗莫司） 凝胶0.2%在日本获批上市，用于治疗结节性硬化综合征中的血管纤维瘤。
结节性硬化症是一种罕见的遗传疾病，可导致发育障碍和肿瘤病变覆盖整个身体，如大脑、皮肤和肾脏。其中，皮肤病变如血管纤维瘤经常发生，症状在青春期变得明显，给病人降低他们的生活质量。然而，目前的治疗方法是侵入性的，例如手术或激光治疗难以用于幼儿或发育障碍患者。
Nobelpharma利用这项研究的结果，对0.2%的Rapalimus凝胶进行了三期比较试验和长期剂量试验，以验证其有效性和安全性，并于2017年10月成为世界上第一个申请上市批准的药物，并在不到6个月的短时间内于2018年3月获得该药物的批准。
Rapalimus（0.2%拉帕林凝胶）是第一个在2015年10月获得SAKIGAKE指定的药物，然后在2015年12月获得孤儿药地位。 在最初的发展阶段，国家研发机构新能源和工业技术发展组织（NEDO）提供了支持，在后期阶段，国家研究开发机构国家生物医药创新、健康和营养研究院提供了支持。
Rapalimus（Sirolimus，西罗莫司）凝胶0.2%是唯一一种有可能局部给药的药物，用于治疗面部血管纤维瘤来自结节性硬化症，有望有助于提高质量病人的生命。
附：完整说明书资料:https://www.info.pmda.go.jp/go/pack/4291700Q1028_1_07/?view=frame&style=XML&lang=ja
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General information on Japanese Rapalimus gel 0.2% for skin lesions in tuberous sclerosis (sirolimus, rapamycin)
Package details: 1 tube * 10g
Manufacturer: Nobelpharma Co., Ltd., Japan
Active ingredients: sirolimus (chemical formula C51H79NO13)
Medical effect: Rapalimus gel is effective for the treatment of skin erosions associated with tuberous sclerosis complex.
Contraindications and precautions: do not use for pregnant or breastfeeding women.
Do not use on mucous membrane. When applying around eyes, take care not to get the medicine into your eyes. Do not apply on the injured areas.
If the area of application is exposed to sunlight or ultraviolet rays, allergy-like symptoms may occur. Patient should take measures such as applying sunscreen on and around the application area.
After opening, store in a refrigerator at 2-8 degrees Celsius. Do not freeze.
If an allergic reaction occurs, stop using the medicine and consult with your doctor. If you’re taking any other medication or receiving any other treatment, you have to consult with your doctor before use.
Dosage and administration
Apply an appropriate amount to the affected area 2times a day. In general, the maximum single dose is 0.2g(approx. 0.5 cm) for 5 years old or younger, 0.3g(approx. 0.75cm)for 6to 11years old, and 0.4g (approx. 1 cm) for 12 years old or older.
How effective are Rapalimus gel 0.2% from Japan for skin lesions in tuberous sclerosis (sirolimus, rapamycin)?
Rapalimus gel contains sirolimus, also called rapamycin, a macrolide compound produced the bacterium Streptomyces hygroscopicus. It works by inhibiting a protein kinase called mTOR (mechanistic target of rapamycin) which is activated in patients with tuberous sclerosis complex. As the result, Rapalimus gel suppresses excessive cell proliferation and improves the skin lesions.
Who should use Rapalimus gel 0.2% from Japan?
Rapalimus gel is effective for the treatment of skin lesions associated with tuberous sclerosis complex. Studies of Japanese scientists showed that topical gel with sirolimus is safe and well-tolerated even in long-term (from 52 to 136 weeks) use (M. Wataya-Kaneda, H. Nagai et al. “Safety and Efficacy of the Sirolimus Gel for TSC Patients With Facial Skin Lesions in a Long-Term, Open-Label, Extension, Uncontrolled Clinical Trial”. Dermatology and Therapy, 2020, 10(4): 635–650).
