Chugai Pharmaceutical Co., Ltd. announced that it has obtained approval for manufacturing tocilizumab (genetical recombination) injection, a humanized anti-human IL-6 (interleukin-6) receptor monoclonal antibody, in Japan. The drug, Actemra 200, which will be manufacturered and marketed in Japan for the treatment of Castleman's disease. Tocilizumab is the first antibody drug originating from Japan.
Castleman's disease is a very rare lymphoproliferative disease, first reported in 1956. Its major symptoms are fever, general fatigue, weight loss, skin rash, anemia, splenomegaly, hepatomegaly, and various abnormal laboratory findings. Complications such as amyloidosis, haemolytic anaemia, or interstitial pneumonia have been reported. Although the mechanism of Castleman's disease has not been fully revealed, a large amount of IL-6 is released from enlarged lymph nodes, and excessive IL-6 production is believed to be closely related to the symptoms and pathology of this disease.
Tocilizumab was engineered/discovered by Chugai in collaboration with Osaka University, utilizing genetic recombinant technology to produce humanized monoclonal antibody from mouse anti-IL-6 receptor monoclonal antibody. Tocilizumab competitively blocks IL-6, binding to its receptor inhibiting biological activity of IL-6. Tocilizumab has been developed as an orphan drug for treatment of Castleman's disease since its designation as an orphan drug in December 2000 to meet the unmet medical need.
In the phase II study of tocilizumab performed in Japan, 8 mg/kg was administered every other week, eight times in total. As a result, inflammation markers (CRP, fibrinogen and ESR), general fatigue, anaemia, and hypoalbuminemia improved significantly during treatment with tocilizumab. The results of long-term repeated treatment (maximum: 1,568 days, average: 1,191 days) also significantly maintained the therapeutic effect, including improvement of the inflammation markers. The major adverse events observed were nasopharyngitis, skin rash, abdominal pain, itching, and neutropenia.
In Japan, Chugai is conducting phase III clinical trials for rheumatoid arthritis (RA), and submission for approval is planned in 2006. Phase III studies in RA in countries outside Japan are being performed in collaboration with Roche for more than 4,000 patients in over 20 countries, and filling is planned in 2007.
Improvement of symptoms and findings (e.g. increased C reactive protein, increased fibrinogen, increased erythrocyte sedimentation rate, decreased haemoglobin, decreased albumin, general malaise). Administration should be limited to patients for whom swollen lymph node resection is not indicated.