Trophos SA announced the results from the phase III study of Trophos’ lead compound, olesoxime, in 512 patients with Amyotrophic Lateral Sclerosis (ALS). Olesoxime did not demonstrate a significant increase in survival versus placebo in patients receiving riluzole (Rilutek). A trend was seen on patients’ function as measured by the ALSFRS-R functional rating scale. Olesoxime was very well tolerated.
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.
Trophos continues its ongoing programmes 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 IIa proof-of-concept study of TRO40303 in cardiac ischemia-reperfusion injury (IRI), with results due before end 2012; A planned phase II proof-of-concept trial of olesoxime in Multiple Sclerosis (MS) disease progression (subject to securing outside funding); A research collaboration with Actelion to screen and characterize Actelion compounds using Trophos’ proprietary CNS assay technology.
The inability of olesoxime to show a greater effect on survival for ALS patients above that of riluzole in the phase III 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 II and III, being studied in an ongoing trial, these 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.
The results of this study in ALS are disappointing, above all for the ALS community, who urgently require new therapies that can prolong survival and improve function. We are genuinely proud to have worked closely with this community and our international partners in the MitoTarget project on this important and very well run study,” said Damian Marron, CEO, Trophos. “We remain convinced of the promise of our cholesterol-oxime, mitochondrial pore modulator compounds. We have ensured that Trophos is financed until at least the end of 2013, so that we continue to move forward on our other programs, which address high medical need orphan or niche indications with no existing treatments.”
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 thirty six months before enrolment and receiving standard care. Olesoxime was dosed orally at 330 mg once-a-day.
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.
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 EUR six million.