Actemra®, a Humanized Anti-Human IL-6 Receptor Monoclonal Antibody Obtained Approval for Indications of Rheumatoid Arthritis

Actemra®, a Humanized Anti-Human IL-6 Receptor Monoclonal Antibody Obtained Approval for Indications of Rheumatoid Arthritis, Polyarticular-Course Juvenile Idiopathic Arthritis and Systemic-Onset Juvenile Idiopathic Arthritis

April 16, 2008 (Tokyo) - Chugai Pharmaceutical Co., Ltd. [Head Office: Chuo-ku Tokyo; President: Osamu Nagayama (hereafter, "Chugai")] announced today that the humanized anti-human interleukin-6 (IL-6) receptor monoclonal antibody, Actemra® 200mg for Intravenous Infusion (hereafter, "Actemra®") [generic name: tocilizumab (genetical recombination)] was approved by the Japanese Ministry of Health, Labour and Welfare for additional indications of "rheumatoid arthritis (including prevention of structural damage of joints)," "polyarticular-course juvenile idiopathic arthritis (hereafter, "pJIA")" and "systemic-onset juvenile idiopathic arthritis (hereafter, "sJIA")," as well as additional 80mg and 400mg preparations. Actemra® is marketed in Japan for the indication of "Castleman's disease" since June 2005.

Actemra®, the first antibody drug (humanized monoclonal antibody) originating from Japan, was created by Chugai in collaboration with Osaka University, utilizing genetic recombinant technology to produce a monoclonal antibody against the anti-IL6 receptor. It works by inhibiting biological activity of IL-6 through competitively blocking the binding of IL-6 to its receptor.

Based on the clinical studies conducted in Japan, Chugai filed the application in April 2006, with phase I, phase II and two phase III studies for rheumatoid arthritis, phase III study for pJIA, and phase II and phase III studies for sJIA, together with efficacy and safety data of their extension studies.

Outside of Japan, applications were filed in Europe and the U.S. for Actemra in November 2007, with the results and the interim analysis of phase III clinical studies and extension studies conducted with more than 4,000 rheumatoid arthritis patients in 40 countries worldwide including co-development between Chugai and F. Hoffmann-La Roche Ltd. [Head Office: Basel, Switzerland; CEO: Severin Schwan (hereafter "Roche")]. Following approval in Europe, the product will be co-promoted by Chugai and Roche in the United Kingdom, France and Germany.
 
Rheumatoid arthritis is a systemic inflammatory disease for which the cause is unknown. It appears more commonly in females in their 40s and 50s, and the disease is causing serious psychological and social problems not only for the patients but also for their families, and measures to counter the disease are seriously needed. Juvenile idiopathic arthritis is the collective term for diseases with unknown cause associated with symptoms in joints occurring in children aged below 16. While clinical findings of pJIA have many similarities to rheumatoid arthritis, sJIA is accompanied by systemic symptoms, mostly remittent fever, and is said to be a very severe disease. Patients are often forced to spend a long time fighting the disease, causing various difficulties in social life such as school life and employment.

Chugai focuses on bone and joint diseases area as one of the strategic domains, and hopes to contribute to the treatment by providing new therapeutic options for medical professionals and patients.

[References]

* The underlined descriptions are newly added.

Brand name:
Actemra® 80 mg for Intravenous Infusion
Actemra® 200 mg for Intravenous Infusion
Actemra® 400 mg for Intravenous Infusion

Generic name:
Tocilizumab (genetical recombination)

Indications:
- The following diseases which do not show sufficient response to the existing therapies:
  Rheumatoid arthritis (RA) (including inhibition of progression of structural joint damage), polyarticular-course juvenile idiopathic arthritis (pJIA), and systemic juvenile idiopathic arthritis (sJIA)
- Improvement of various symptoms (e.g. generalised fatigue) and laboratory findings (increased C-reactive protein, fibrinogen, and erythrocyte sedimentation rate, decreased haemoglobin and albumin) associated with Castleman's disease. However, treatment with Actemra® should be limited to patients for whom lymph node resection is not indicated.

Dosage and administration:
1. RA and pJIA:
   The recommended dose of tocilizumab (genetical recombination) is 8 mg/kg as a single intravenous drip infusion administered at 4-week intervals.
2. sJIA and Castleman's disease:
   The recommended dose of tocilizumab (genetical recombination) is 8 mg/kg as a single intravenous drip infusion administered at 2-week intervals. The dosing interval can be shortened to a minimum of 1 week depending on the patient’s disease condition.

Conditions for approval:
Castleman's disease:
 During the reexamination period, all patients treated with Actemra® should be registered as subjects, and post-marketing surveillance of the efficacy and safety of Actemra® including changes in lymph node swelling and effect on progression of complications should be conducted. At the same time, information about efficacy and safety of long-term treatment with Actemra® should also be collected.
RA, pJIA, and sJIA:
 1. After marketing, while data is being gathered for a fixed number of patients, safety and efficacy data for Actemra® should be swiftly collected by conducting a drug use-results survey of all cases and necessary measures should be taken for the proper use of Actemra®.
 2. A large-scale post-marketing surveillance should be conducted with a comprehensive investigation of the safety of Actemra® including the safety of long-term treatment and occurrence of infections, etc.

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