Drugs Xagena
RPC1063 is a novel, oral, once daily, specific and potent modulator of the sphingosine 1-phosphate 1 receptor ( S1P1R ) pathway, which is a validated G protein-coupled receptor ( GPCR ) target for the treatment of relapsing-remitting multiple sclerosis.
Of the five receptor subtypes in the sphingosine 1-phosphate pathway, evidence suggests that the S1P1R specifically is responsible for the efficacy of this therapeutic mechanism in autoimmune disorders such as relapsing-remitting multiple sclerosis and inflammatory bowel disease.
The S1P1R is expressed on lymphocytes, including those responsible for the development of disease ( autoreactive lymphocytes ).
S1P1R modulation causes selective and reversible retention, or sequestration, of circulating lymphocytes in peripheral lymphoid tissue. This sequestration is achieved by modulating cell migration patterns ( known as lymphocyte trafficking ), specifically preventing self-targeting, or autoreactive, lymphocyte migration to areas of disease inflammation, which is a major contributor to autoimmune disease.
S1P1R modulation may also involve the reduction of lymphocyte migration into the central nervous system ( CNS ), where certain disease processes take place. This therapeutic approach diminishes the activity of autoreactive lymphocytes that are the underlying cause of autoimmune disease.
RPC1063 for relapsing-remitting multiple sclerosis
Relapsing multiple sclerosis is a chronic autoimmune disorder of the central nervous system, characterized by recurrent acute exacerbations ( relapses ) of neurological dysfunction followed by variable degrees of recovery with clinical stability between relapses ( remission ).
The CNS destruction caused by autoreactive lymphocytes can lead to the clinical symptoms, such as numbness, difficulty walking, visual loss, incoordination and muscle weakness, experienced by patients. The disease invariably results in progressive and permanent accumulation of disability and impairment, affecting adults during their most productive years.
Relapsing-remitting multiple sclerosis disproportionately affects women, with its peak onset at ages 29-30.
RPC1063 S1P1R modulation causes selective and reversible retention, or sequestration, of circulating lymphocytes in peripheral lymphoid tissue.
Reduction in peripheral lymphocyte count serves as a validated pharmacodynamic measure ( biomarker ) for the S1PR modulator class in relapsing-remitting multiple sclerosis. Specifically, certain threshold levels of reduction correlate with a standard phase 2 efficacy endpoint of significant reduction in the cumulative number of total Gadolinium enhancing lesions determined by magnetic resonance imaging ( MRI ) as well as a standard phase 3 efficacy endpoint of significant reduction in annualized relapse rate ( ARR ).
It has been demonstrated dose-dependent lymphocyte count reduction to target levels with RPC1063 in a phase 1 study.
RPC1063 is currently in the phase 2 portion of an accelerated design phase 2/3 study for relapsing-remitting multiple sclerosis which was designed in consultation with the FDA ( Food and Drug Administration ).
This study, a placebo-controlled ( phase 2 ) trial called the RADIANCE trial, is a randomized, double-blind comparison.
The primary objective is to demonstrate the superior clinical efficacy of RPC1063 compared to placebo by showing a reduction in the cumulative number of new Gadolinium enhancing lesions from week 12 to week 24 of study treatment.
RPC1063 for inflammatory bowel disease
Inflammatory bowel disease ( IBD ) is comprised of two chronic, autoimmune, gastrointestinal ( GI ) inflammatory disorders; ulcerative colitis ( UC ) and Crohn's disease ( CD ).
Ulcerative colitis is a GI inflammatory disorder involving ulcers in the colon and is characterized by a chronic course of remissions and exacerbations. Patients suffer from a multitude of GI symptoms, including diarrhea, rectal bleeding and abdominal pain.
Aa phase 2 study will assessed RPC1063 as an induction therapy in patients with moderately-to-severely active ulcerative colitis called TOUCHSTONE.
TOUCHSTONE is a multi-national, multi-center, double-blind, randomized, placebo-controlled study investigating the effect of two active doses ( low dose and high dose ) of RPC1063 versus placebo.
The primary objective of TOUCHSTONE is to compare the efficacy of RPC1063 for the induction of clinical remission in patients with moderately to severely active ulcerative colitis at eight weeks of treatment. ( Xagena )
Source: Receptos, 2014
XagenaMedicine_2014
