close

Clinical Trials

Date: 2011-08-02

Type of information: Results

phase: 2b

Announcement: results

Company: Actelion (Switzerland)

Product: ponesimod

Action mechanism:

immunomodulator/ S1P1 immunomodulator. Sphingosine-1-phosphate (S1P) is a sphingolipid released by erythrocytes, platelets, mast cells and other cell types. It is currently established that S1P stimulates at least five different cell surface resident G-protein coupled receptors (GPCRs) - S1P1,2,3,4, and 5. Activation of these GPCRs mediates a complex variety of biological responses such as lymphocyte migration, endothelial cell proliferation, blood vessel constriction and heart rate modulation. Ponesimod is an orally active, selective S1P1 immunomodulator. It prevents lymphocytes from leaving lymph nodes, thereby reducing circulating blood lymphocyte counts and preventing infiltration of lymphocytes into target tissues. The lymphocyte count reduction is rapid, dose-responsive, is sustained with continued dosing and quickly reversed upon discontinuation. Ponesimod does not cause lymphotoxicity: it does not destroy lymphocytes or interfere with their cellular function. Other blood cells e.g. cells of the innate immune system are unaffected and remain available to fight off infection. Ponesimod is therefore considered a promising new oral agent for the treatment of a variety of autoimmune disorders.

Disease: relapsing-remitting multiple sclerosis

Therapeutic area: Autoimmune diseases - Neurodegenerative diseases

Country:

Trial details:

Latest news:

The primary endpoint - reduction in the number of new active inflammatory lesions in the brain - has been met with Actelion’s selective S1P1 receptor agonist, ponesimod, in a Phase IIb dose-finding study in patients with relapsing-remitting multiple sclerosis. The study assessed efficacy, safety and tolerability of three ponesimod doses (10 mg, 20 mg or 40 mg) versus placebo, administered orally once daily for 24 weeks. With 464 patients enrolled, this is the largest ever dose-finding study conducted in this autoimmune disorder of the central nervous system.
In this study, ponesimod significantly reduced the cumulative number of new active lesions on monthly magnetic resonance imaging (MRI) brain scans performed from weeks 12 to 24, with the most effective dose at p<0.0001.
As in previous healthy volunteer studies with ponesimod, average lymphocyte counts in patients with relapsing multiple sclerosis were reduced in a dose-dependent fashion. Average lymphocyte counts returned to baseline values within a week in patients who discontinued treatment with ponesimod.
Despite the small overall number of confirmed relapses in this study, there was also a clinically meaningful effect observed on annualized relapse rate, an important secondary endpoint. Multiple sclerosis is most commonly diagnosed in young adults and is associated with diverse recurrent neurological symptoms.
Ponesimod exhibited an adverse event pattern in this study that, if confirmed in the upcoming Phase III program, would give ponesimod a competitive safety and tolerability profile.
Once full data analysis has been concluded, Actelion will discuss the details of the upcoming Phase III program with health authorities worldwide. At a later stage, Actelion will discuss and present the findings of this Phase IIb study as well as the Phase III program in scientific presentations and publications.

Is general: Yes