BASEL/REINACH, Switzerland—Nitec Pharma AG announced positive results from the second pivotal phase III trial for its lead product, Lodotra™ and will use those data plus data from the initial phase III study to file for US marketing approval for the delayed-release, low-dose prednisone in rheumatoid arthritis (RA).
Lodotra is taken at bedtime. The formulation releases prednisone during the night at around 2am, enabling suppression of nocturnal proinflammatory cytokines. This results in an effective relief of the early morning symptoms of RA, in addition to the well-established treatment effects of glucocorticoids.
The CAPRA-2 study (Circadian Administration of Prednisone in Rheumatoid Arthritis-2) was a 12-week, multicenter, double-blind phase III trial evaluating the safety and efficacy of Lodotra for the treatment of RA. CAPRA-2 included 350 patients with RA inadequately controlled by DMARD therapy. Patients were randomized to receive either Lodotra (5mg once daily), or placebo in addition to their existing therapy.
The primary efficacy endpoint was the ACR-20 response rate, which is defined as at least a 20% improvement in a number of disease-specific criteria. The key secondary endpoint was the change in the duration of morning stiffness.
Lodotra-treated patients showed an ACR-20 response of 49% compared to 29% in the placebo group (p=0.0002). Morning stiffness was reduced 44% in the Lodotra group vs. 21 % in the placebo group (p=0.0008). The number of adverse events was low and comparable in both groups.
The earlier CAPRA-1 pivotal phase III trial had shown superiority of Lodotra over standard prednisone treatment.
Dr. Anders Harfstrand, CEO of Nitec commented: "We are delighted to report successful and very positive outcomes of the CAPRA-2 study. These strongly underline the benefits of Lodotra in the treatment of RA. The study confirms clearly that the innovative delivery system of Lodotra is able to adapt the timing of glucocorticoid treatment to a patient's circadian rhythm in order to improve the efficacy and safety of prednisone. CAPRA-2 is the first pivotal phase III study to demonstrate the ACR-20 response of a very low dose of prednisone as a primary endpoint. Following the successful European launches of Lodotra and the positive feedback that we have received from RA specialists, we look forward to completing the regulatory process in the US."
The drug is marketed in Germany by Merck KGaA, which holds the exclusive distribution rights for Germany and Austria. In April 2009 Mundipharma acquired the distribution rights in the rest of Europe. Nitec retains all commercialization rights for the US and rest of the world.
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