Teva Pharmaceutical Industries Ltd. and Active Biotech AB announced that data from a 36-week, randomized, doubleblind, placebo-controlled Phase IIb study demonstrated that an oral 0.6 mg dose of laquinimod given daily significantly reduced magnetic resonance imaging (MRI) disease activity by 38 percent in RRMS patients and was well tolerated.
In addition, there was a favorable trend towards reducing annual relapse rates, the number of relapse-free patients and time to first relapse compared with placebo. Treatment with a 0.3 mg dose showed no statistical significant difference compared with placebo.These data were presented at the 59th Annual Meeting of the American Academy of Neurology (AAN) in Boston, MA, April 28 ? May 5, 2007. “Current RRMS options are effective for the treatment of the disease, but an oral therapy such as laquinimod would represent a milestone for patients as it would provide them with a completely unique, non-invasive method of drug delivery,” said Giancarlo Comi, M.D., Director of Department of Neurology and Institute of Experimental Neurology,
Universita Vita-Salute, San Raffaele, Milan, Italy. “Preliminary studies have already demonstrated the positive effect of laquinimod versus placebo, but these new data confirmed that a higher dose was even more effective and remained well tolerated.” The 36-week study evaluated the effect of oral daily 0.3 and 0.6 mg doses of laquinimod on MRI-monitored disease activity in patients with RRMS. The majority of the patients who participated in the study continued treatment with laquinimod in an ongoing, blinded 9 month extension study. This extension study is followed by an open label study where patients will receive 0.6 mg laquinimod for an additional 24 months.
“The results of this study, which once again demonstrate the efficacy and tolerability of once-daily oral laquinimod, are very exciting for the MS community?both patients and researchers,” said Shlomo Yanai, President and CEO of Teva Pharmaceutical Industries Ltd. “Teva will soon initiate Phase III studies to confirm oral laquinimod’s therapeutic benefits, and we expect to begin enrollment of the trial later this year.”
About the Study Study participants were required to have experienced one or more relapses in the year prior to entry and at least one Gd-enhancing lesion at screening. The patients (n=306) in the study were randomized to receive placebo (n=102), 0.3 mg dose of laquinimod (n=98) or 0.6 mg dose of laquinimod (n=106). At entry, active treatment and placebo groups were comparable for demographic, clinical and MRI characteristics.
Patients were assessed clinically and by MRI scan at week -4, baseline, and monthly from weeks 12 to 36. The primary outcome of the study was the cumulative number of Gdenhancing lesions at weeks 24, 28, 32 and 36. Secondary outcomes of the study included additional MRI metrics and confirmed relapse rate. The laquinimod 0.6 mg dose showed a reduction compared with placebo in the cumulative number of enhancing lesions per scan in the last four scans (mean SD= 2.6 5.3 vs. 4.2 9.2, p = 0.0048); treatment with the 0.3 mg dose showed no significant difference. Significant differences in favor of the 0.6 mg dose were found for most examined secondary and exploratory MRI-based outcome measures. Trends favored the group receiving the 0.6 mg dose on measures of annual relapse rate (0.52 +/- 0.92 vs. placebo 0.77 +/- 1.25; p = 0.21), relapse-free subjects (70.8 percent vs. 62.7 percent; p = 0.33) and time to first relapse (p = 0.14). Treatment with both 0.3 and 0.6 mg doses of laquinimod were well tolerated with only some transient and dose-dependent increases in liver enzymes. About laquinimod Laquinimod is a novel once-daily, orally administered immunomodulatory compound developed as a disease modifying treatment for multiple sclerosis (MS). Active Biotech developed laquinimod and licensed it to Teva Pharmaceutical Industries, Ltd. in June 2004. A previous 24-week Phase IIa trial conducted by Active Biotech demonstrated that oral 0.3 mg laquinimod given daily was well tolerated and reduced the formation of active lesions in RRMS. To date, 460 MS patients have received laquinimod in various clinical trials.