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Laquinimod

Laquinimod is an orally administered immunomodulator being studied in patients with RRMS and SPMS. The anti-inflammatory properties of laquinimod are thought to be secondary to downregulation of MHC class II gene transcription factors, stimulation of neurotrophic factors, activation of the anti-inflammatory IL-4 pathway in CD4+ T cells, promotion of apoptosis in CD8+ T cells and B cells, and suppression of the metabolic activity of CD14+ and natural killer cells [Thöne et al. 2011]. Therefore, it is proposed that laquinimod acts by affecting the Th1 to Th2 cytokine shift. Two phase II trials in patients with RRMS and SPMS have been completed, with varying results [Comi et al. 2008; Polman et al. 2005]. In the phase III Assessment of Oral Laquinimod in Preventing Progression in Multiple Sclerosis (ALLEGRO study), laquinimod significantly improved clinical and radiologic outcomes, resulting in a 23% reduction in relapse rate, and a 37% reduction in mean cumulative number of Gad+ lesions [Comi et al. 2012b]. The Benefit Risk Assessment of Avonex and Laquinimod (BRAVO) study is another phase III study comparing laquinimod at 0.6 mg/day with weekly intramuscular IFN-β1a at 30 μg in patients with RRMS. At the 5th Joint Triennial Congress of the European and Americas Committees for Treatment and Research in Multiple Sclerosis (ECTRIMS/ACTRIMS), the results of a randomized, placebo-controlled, double-blind, active-comparator phase III study, BRAVO, were presented. This study did not achieve its primary endpoint of reducing the ARR. Laquinimod appears to be well tolerated, with only transient and dose-dependent increases in liver enzymes [Vollmer et al. 2011].


Zamítnuté léky:

Nerventra (laquinimod) - tabletkový lék podávaný 1x denně. Výbor pro humánní léčiva (CHMP) doporučil Evropské komisi v lednu 2014 neschválit toto léčivo pro evropský trh a po odvolání výrobce potom v květnu 2014 toto své doporučení potvrdil. Poukázal přitom na zvýšený výskyt rakoviny u laboratorních zvířat, na nichž bylo léčivo dlouhodobě testováno a na poškození plodu zvířat, která při této terapii zabřezla. Studie na zvířatech navíc naznačují, že některé škodlivé účinky léčiva se mohou projevit i se zpožděním, tedy až v pozdějším životě dítěte pacientky, která by užila Nerventru v těhotenství.