Date: 2011-12-13
Type of information:
phase: 3
Announcement: results
Company: Trophos (France)
Product: olesoxime
Action mechanism: Olesoxime is one of the cholesterol-oxime compound family of mitochondrial pore modulators, developed for their ability to promote the function and survival of neurons and other cell types under disease-relevant stress conditions through interactions with the mitochondrial permeability transition pore (mPTP). Olesoxime also has the ability to promote remyelination in addition to providing neuroprotection.
Disease: amyotrophic lateral sclerosis
Therapeutic area: Neurodegenerative diseases - Neuromuscular diseases
Country: France, Germany, UK, Belgium, Spain
Trial
details: The study was an 18-month randomized, parallel group, double-blind, placebo-controlled trial evaluating the efficacy and safety of olesoxime against placebo in patients treated with riluzole. The study was conducted in 512 patients diagnosed with ALS between six and 36 months before enrollment and receiving standard of care. Olesoxime was dosed orally at 330 mg once-a-day.
The study was undertaken in 15 centers in France, Germany, UK, Belgium and Spain as part of a three-year collaborative project named MitoTarget (Grant Agreement No: HEALTH-F2-2008-223388) for which the European Commission has awarded a grant of nearly € 6 million.
Latest
news: * On December 13, 2011, Trophos has announced that olesoxime did not demonstrate significant benefit on the primary endpoint of survival after 18 months of treatment over that of riluzole. A trend was seen on the secondary criteria of ALSFRS-R on a pre-specified analysis after nine months of treatment. Olesoxime was very well tolerated with a side effect profile similar to riluzole plus placebo. Full results will be published in scientific journals and congresses in due course. Trophos continues its ongoing programs and has financing secured to at least the end of 2013. These programs include: · An ongoing pivotal trial of olesoxime in Spinal Muscular Atrophy (SMA) with results due in the second half of 2013; · An ongoing phase 2a proof-of-concept study of TRO40303 in cardiac ischemia-reperfusion injury (IRI), with results due before end 2012; · A planned phase 2 proof-of-concept trial of olesoxime in Multiple Sclerosis (MS) disease progression (subject to securing outside funding);
The inability of olesoxime to show a greater effect on survival for ALS patients above that of riluzole in the phase 3 trial is most likely because the disease process is already so severe and rapidly progressing by the time of diagnosis that any further benefit of olesoxime over that of riluzole cannot be detected. Indeed, it is known that in the most widely used ALS model, over 50 per cent of the motor neurons and neuromuscular connections have already been lost by the time the first symptoms appear. Of Trophos' other target indications for olesoxime, SMA type 2 and 3, being studied in an ongoing trial, differ in that disease progresses slowly over many years. Progressive MS is again different as neuronal degeneration correlated with disease progression only sets in after symptoms appear.
Following receipt of these results, Actelion has informed Trophos of its decision to not exercise its exclusive option under the July 2010 Acquisition Option Agreement between Trophos and Actelion. In July 2010, Actelion and Trophos entered into an agreement whereby Actelion, in exchange for an option payment of €10 million, obtained an exclusive option to acquire, at predetermined terms, privately-held Trophos pending the outcome of the Phase III study with olesoxime in ALS. The payment was recorded as a financial investment and, following the decision not to proceed with the acquisition, the option will be written-off within financial expenses.
* On September 22, 2011, Trophos has announced that the last patient has now completed the major pivotal phase three efficacy study of olesoxime in amyotrophic lateral sclerosis. Over 500 patients were enrolled in the study and the last patient completed the prescribed study protocol procedures on 15th September. Work is now ongoing to finalise the analysis of the data. Efficacy and safety top-line results are expected in the fourth quarter of 2011.
The study is part of the EU FP7 three-year MitoTarget project, comprising a pan-European consortium of leading experts in ALS and spearheaded by Trophos. The trial protocol has benefited from EMA Scientific Advice procedure.
