January 18, 2024
Nobelpharma Co., Ltd.

mTOR inhibitor “RAPRLIMUS®” Approved for
Additional Indication for Tablets 1 mg andAdditional Formulation of Granule 0.2%
Nobelpharma Co., Ltd. (Headquarters: Chuo-ku, Tokyo, Managing Director & CEO: Jin
Shiomura) announced today that an additional indication for the company’s product
RAPALIMUS® Tablets 1 mg and an additional formulation of granules 0.2% have been
approved.
We are deeply grateful for all of the efforts of the principal investigator, Dr. Michio Ozeki,
Department of Pediatrics, Gifu University and many other physicians participated in theinvestigator initiated studies and the specified clinical researches, the cooperation from thepatients entered in the clinical trials, as well as the assistance from Japan Agency for Medical
Research and Development (AMED) and National Institutes of Biomedical Innovation, Healthand Nutrition, owing to which the additional indication of “intractable vascular tumors andvascular malformations” and the additional formulation for the same indication were approved.
(RAPALIMUS granules 0.2% is under preparation for launch.)
Indications
RAPALIMUA tablets 1 mg

〇 lymphangioleiomyomatosis〇 Following intractable vascular anomalies
lymphangioma (lymphatic malformation), lymphangiomatosis,
Gorham’s disease, lymphangiectasia
hemangioendothelioma, tufted angioma, arteriovenous
malformation, blue rubber bleb nevus syndrome, combined
vascular malformation, Klippel-Trenaunay-Weber syndrome

RAPALIMUS granules 0.2%

〇Following intractable vascular anomalies
lymphangioma (lymphatic malformation), lymphangiomatosis,
Gorham’s disease, lymphangiectasia
hemangioendothelioma, tufted angioma, arteriovenous
malformation, blue rubber bleb nevus syndrome, combined
vascular malformation, Klippel-Trenaunay-Weber syndrome* Newly approved additional indications and newly approved formulation are underlined.
〇 “Vascular Tumors and Vascular Malformation (Vascular Anomalies)”“Vasculature” includes “blood vessels” and “lymphatic vessels.”

“Vascular tumors” mainly means angioma that is made of quickly dividing cells of blood vessel
walls, while the size of which tends to change in size within a short period as the tumor cells
grow and involute. On the other hand, “vascular malformation” differs from tumors and does
not change much in size but does not disappear either. In a longer term, it is said to enlarge as thepatients grow and may become worse driven by certain events, including age of puberty,
pregnancy, infection and trauma.1)〇 Refractory Vascular Anomalies
Stubborn cases are called “refractory” and the treatment may become lengthy depending on thesites, size and symptoms. The symptoms of each case vary from continuing pain andhemorrhagic tendency to breathing trouble due to lesion sites. Some may interfere with certain
aspects of life and cause aesthetic problems.1)〇 Treatment
The therapeutic approaches for vascular anomalies include surgical, laser, and intravasculartreatments. As a course of medication for symptoms, pain relief (such as acetaminophen) andhemostat (such as tranexamic acid) have been used. For the disorder itself, various moleculartargeted drugs is recently becoming high-profile, while steroids and anticancer drugs were used tobe prescribed.1)〇 Number of Refractory Vascular Anomalies
It is estimated approximately 6,000 – 8,000 people in Japan have intractable vascular tumor or
intractable vascular malformation (including arteriovenous malformation and Sturge-Webersyndrome which are not the indications of this product).
We hope the RAPALIMUS tablets become one of the treatment options and can be of any help
for refractory vascular anomaly patients.
We have also created the web site for lymphatic disorder in Nobelpharma corporate site.
https://www.nobelpharma.co.jp/general/lymphangioma/1)

Site for Information of Drug Therapy Working Group for Intractable Vascular Anomalies
https://cure-vas.jp/

We are determined to continue contributing to society by providing critical but neglectedpharmaceuticals and medical devices.

[Contact for Inquiries]
Noboru Kudo, Head of Communications
Nobelpharma Co., Ltd.
1-17-24, Shinkawa, Chuo-ku, Tokyo 104-0033
Tel: 03-6670-3800