Discontinuation of higher doses in Phase III trials for laquinimod for MS.- Teva + Active Biotech
Teva Pharmaceutical Industries Ltd. and Active Biotech announced the discontinuation of higher doses of laquinimod in two ongoing studies in multiple sclerosis after the occurrence of cardiovascular events, none of which was fatal, in eight patients. The change comes at the recommendation of the data monitoring committee (DMC) overseeing two active clinical studies in MS. The DMC identified an imbalance in the number of cardiovascular events in the studies. Seven events were observed in patients receiving laquinimod daily at 1.2mg for treatment of relapsing-remitting MS (RRMS) in the CONCERTO trial. No events occurred in the 0.6mg or placebo groups. CONCERTO has 2,199 patients with 3,070 years of patient experience. One event was observed in the 1.5mg daily-dose arm of the ARPEGGIO trial in primary-progressive MS (PPMS). ARPEGGIO has enrolled 191 patients and has 35 years of patient experience. Teva is notifying trial sites to discontinue the higher doses immediately in both trials and will encourage participants to continue follow ups. Both trials, CONCERTO and ARPEGGIO, are continuing the lower-dose arms (0.6mg daily), and participants in the trials will be provided with an update to confirm re-consent for participation. The DMC did not identify a cardiovascular signal with the lower dose but recommended long-term monitoring.
Comment: Laquinimod is the intended successor to blockbuster Copaxone (glatiramer acetate) that is now off patent as a treatment for Multiple Sclerosis and faces competition from biosimilar Glatopa from Sandoz. The response of Teva has been to substitute Copaxone 40 mg, which is taken thrice weekly, for the now generic 20 mg version.
Comment: The appearance of CV risks in Phase III trials and withdrawal of the higher doses is a setback. There have been years of delay in development of the drug and several disappointing clinical trials and a rejection by EMA. Teva expects final data in 2017 and an approval in 2018. The question is whether the lower doses will support competitive efficacy.
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