Linomide in relapsing and secondary progressive MS

Abstract

MS patients may be more prone to develop important linomide treatment-related adverse events than other previously studied patients. However, linomide may be a potentially more toxic drug than was suspected from observations made in smaller studies for other indications. Phase III trials may identify infrequent and important toxicities that may not be anticipated by phase I and II trials.

Open-label, clinical phase I studies of tasquinimod in patients with castration-resistant prostate cancer

“…Structurally, tasquinimod is related to roquinimex (linomide), which was tested in a series of phase II and III trials in patients with advanced renal cell carcinoma Pawinski et al, 1997) and in those with multiple sclerosis (MS) (Noseworthy et al, 2000). In patients with renal cell cancer, the efficacy was modest with influenza-like symptoms of myalgia, arthralgia and fatigue being the most common adverse events.…”

Cytochrome P450 3a4 Is the Major Enzyme Responsible for the Metabolism of Laquinimod, a Novel Immunomodulator

“…Laquinimod (ABR-215062, N-ethyl-N-phenyl-5-chloro-1,2-dihydroxy-1-methyl-2-oxo-3-quinoline-carboxamide) represents a novel orally active immunomodulator similar in structure to the previously clinically evaluated analog, roquinimex (Linomide) (Andersen et al, 1996;Karussis et al, 1996;Noseworthy et al, 2000;Tan et al, 2000;Tuvesson et al, 2000). Both roquinimex and laquinimod have been found to effectively inhibit disease in both acute experimental autoimmune encephalomyelitis and chronic relapsing experimental autoimmune encephalomyelitis, two mouse models for the study of multiple sclerosis (MS) (Karussis et al, 1993a,b;Brunmark et al, 2002;Jönsson et al, 2004).…”

Managed Approaches to Multiple Sclerosis in Special Populations

“…Laquinimod is a derivative of linomide, a structurally related compound that had previously reached phase 3 studies in patients with MS, but whose clinical development was halted due to such adverse effects as serositis and myocardial infarctions. [21][22][23] Laquinimod, a pharmacologically and chemically distinct molecule, was selected based on structure/ function testing as well as efficacy and safety in experimental autoimmune encephalomyelitis (EAE) models. 24,25 Although the exact mechanism(s) of action of laquinimod is/are incompletely understood, this drug has been reported to (a) decrease secretion of proinflammatory cytokines and enhance secretion of antiinflammatory cytokines and (b) upregulate brainderived neurotrophic factor.…”