FDA Accepts Lodotra New Drug Application for Rheumatoid Arthritis

Horizon Pharma announced last Tuesday that the FDA had accepted its new drug application for Lodotra, a delayed-release formulation of low-dose prednisone, for treatment of rheumatoid arthritis in adults. The agency expects to reach a decision on whether to approve the drug by the end of July 2012.

The company’s application was based primarily on the results of the Circadian Administration of Prednisone in RA (CAPRA-2) trial, a 12-week Phase 3 trial including 350 RA patients, 231 of whom received Lodotra, and 119 placebo. (Both treatment groups also received standard RA treatment with a disease-modifying anti-rheumatic drug.)

The trial found a statistically significant improvement in ACR20 response for Lodotra patients (48.0%) compared with placebo patients (29.4%), the primary study end point; a statistically significant improvement in ACR50 response compared with placebo (22.3% vs. 10.1%); improvement in the ACR70 response (7.0% vs. 2.5%); and statistically significant reduction in duration of morning stiffness compared with those taking placebo (median relative change: 55.2% vs. 34.6%).

Also included in the application were data from the CAPRA-1 study, a 12-week trial in Europe of 288 RA patients, which compared night-time administration of Lodotra (144 patients) with morning administration of immediate-release prednisone (144 patients) at the same individual dose (average dose 6.7 mg).

Results from CAPRA-1 showed a statistically significant reduction in duration of morning stiffness for those taking Lodotra compared with those taking immediate-release prednisone (22.7% vs. 0.4%) and a statistically significant reduction in IL-6 levels of those taking Lodotra (29% relative median change) compared with no change in IL-6 levels of those taking immediate-release prednisone.

Patients in CAPRA-1 were followed in a nine-month, open-label extension study including 249 RA patients, 219 of whom completed the study. Those continuing with Lodotra treatment had a 55% reduction in duration of morning stiffness. Those newly assigned to Lodotra had a 45% reduction in duration of morning stiffness and had a 50% median reduction in IL-6 levels.