The Nordic Pharma Group announces a strategic collaboration with Nippon Kayaku on Spanidin® (gusperimus) in selected territories outside Japan, including Europe.
Tokyo, Japan and Paris, France (December 20, 2010). Nippon Kayaku (NK) and the Nordic Pharma Group (Nordic) have signed a licensing agreement under which NK grants exclusive rights to NORDIC for the development and commercialisation of Spanidin® (gusperimus) in selected territories outside of Japan, including Europe.
Spanidin® is an immunosuppressive agent developed and commercialised in Japan by NK in acute and accelerated rejection crisis after renal transplantation. The product has also obtained promising results and orphan medicinal product status in Europe for the treatment of Wegener´s Granulomatosis (WG).
Under this agreement, Nordic will design and execute the global clinical development of Spanidin®, which includes a pivotal, comparative Phase III study for patients suffering from WG relapse. Nordic will also be responsible for the regulatory filing and commercialisation of the product in the relevant countries. NK will ensure production of the active ingredient until registration and beyond.
Spanidin® has the potential to offer a treatment for relapsing WG patients, who currently have no approved drug to cure their disease.
With this new agreement, Nordic is actively pursuing its strategy to bring innovative drugs to the market in specialized therapeutic areas that have specific, unmet medical needs.
About Wegener’s Granulomatosis
Wegener’s Granulomatosis is a form of primary, systemic vasculitis with granulomatous inflammation of the respiratory tract combined with necrotising vasculitis of the small to medium sized blood vessels. Although it primarily involves the respiratory tract, lungs and kidneys, almost any organ can be affected. WG is a rare disease with an estimated prevalence of 42 to 63 per million inhabitants in the European Union. In the past, prognosis was poor, with a mortality rate of 80% within a year.
The development by Fauci and co-workers in 1983 of a treatment regimen using cyclophosphamide (CYC) and prednisone improved the prognosis, and the disease became one marked by remissions and relapses (i.e., recurrence or new onset of disease activity represented by active inflammation) associated with significant morbidity. Improvement or remission can be achieved in 75% to 90% of patients. However, WG remains life threatening with frequent relapses, and treatment, which in itself is associated with high morbidity and mortality, is needed on a long-term basis.
To induce remission in naive patients, the first treatment of choice is oral CYC in combination with corticosteroids. CYC is associated with an increased risk of bladder cancer. The estimated incidence of bladder cancer was 16% after 15 years, and the risk is proportional to the cumulative CYC dose. CYC can cause gonadal toxicity and reproductive failure, is known to be hepatotoxic, and can cause bone marrow toxicity.
Approximately 10 % of patients do not respond to CYC and corticosteroids. Furthermore, some patients cannot tolerate the treatment or continue to relapse.
Spanidin® (gusperimus) is a chemically synthesised immunosuppressant, which was developed in collaboration with Institute of Microbial Chemistry and Takara Shuzo. It suppresses the functions of various immunocompetent cells, i.e., T-lymphocytes, B-lymphocytes, macrophages and dendritic cells. Through its specific binding to Hsp70, a heat shock protein, it inhibits the chaperone function of Hsp70 family proteins, the translocation of NF-κB to the nucleus and the loading of antigenic peptides into MHC molecules. It also inhibits the activation of dendritic cells by Hsp70. This mechanism is unique to gusperimus and different from presently used immunosuppressive agents, such as calcineurin inhibitors (cyclosporin and tacrolimus), mammalian TOR (sirolimus) and anti-metabolites (mycophenolate mofetil).
Gusperimus is effective as a single prophylactic and therapeutic agent in prolonging allograft survival in mice, rats, dogs, and non-human primates. Furthermore, combining gusperimus with other immunosuppressants, such as steroids, cyclosporin and tacrolimus, is useful for prolonging allograft survival rates.
Gusperimus is also effective in various autoimmune animal models, such as rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis, crescentic glomerulonephritis, Type I diabetes, uveitis, idiopathic thrombocytopenia purpura, and colitis.
An early phase II study was performed in Germany from 1999 to 2000 on 20 patients with intractable ANCA-associated vasculitis (19 Wegener’s Granulomatosis patients and 1 microscopic polyangiitis patient). Gusperimus was intravenously (only in the first week of the first course) or subcutaneously administered once a day at 0.5 mg/kg/day for 28 days. If the White Blood Cell (WBC) count dropped to 3000/μl during the period, administration was suspended until a least a WBC of 4000/μl was reached again. This was repeated for up to 6 cycles. During the study, no other immunosuppressants, except steroids, were allowed. Improvement during treatment was achieved in 70% of the cases. Most of the patients experienced transient leucopoenia of a similar pattern (decrease after administration and recovery before next course) during the study. No mortality or septicaemia was observed. Mild to moderate infections, mainly of the respiratory tract, were observed but resolved under appropriate treatment without after-effects.
A late Phase II study was performed in Europe from 2003 to 2006 on 45 patients with refractory Wegener’s Granulomatosis. Gusperimus was self-administered subcutaneously at 0.5 mg/kg/day for 21 days followed by a minimum, seven-day rest period. Each patient was supposed to receive six treatment cycles. The response rate as per the study protocol definition was 92%, with complete remission in 46% patients and partial remission in 46% patients. The most clinically significant side effects were reversible leucopoenia, neutropoenia and anaemia. All side effects were manageable and reversible.