Trophos announces positive interim review in pivotal study of olesoxime in Spinal Muscular Atrophy

Trophos SA, a clinical stage pharmaceutical company developing innovative therapeutics from discovery to clinical validation for under-served medical needs in neurology and cardiology, announces today the completion of the interim analysis of the pivotal efficacy study of olesoxime in the rare neurodegenerative condition Spinal Muscular Atrophy (SMA). 

The independent Data Monitoring Committee (DMC) has reviewed the treatment effect at one year on the primary outcome measure of efficacy, change in motor function using the MFM scale, together with the latest safety report including electrocardiogram traces, periodic laboratory findings, haemostatic parameters and serious adverse events listings for all participants. Based on the trial stopping criteria as defined in the protocol as well as no safety concerns related to olesoxime treatment, their recommendation is to continue the study as planned.

An interim analysis of efficacy, as included in the study protocol, has been conducted after all participants have been treated for one year. Over 160 patients have been recruited into the trial between October 2010 and September 2011 (see press release of  September 8, 2011). Following the recommendations of the DMC, the study will continue until all participants have been treated for two years with the last patient out scheduled for September 2013. Top line results are expected by the end of 2013.

The trial is substantially funded by Trophos’ partnership with the Association Francaise contre les Myopathies (AFM-Telethon) (see press release of March 19, 2009). The trial protocol has benefited from the EMA protocol advice procedure.

“The approval from the DMC to continue the trial based on the interim analysis for this innovative treatment of SMA is perfect news at this stage. We confirmed the good safety of olesoxime treatment and we look forward to completing the two year treatment period to report efficacy in these SMA patients,” said Rebecca Pruss, chief scientific officer at Trophos. “SMA is a progressive and disabling neuromuscular disease. Treatments are desperately needed that slow down or prevent the loss of neuromuscular function in SMA patients. This study of olesoxime has been conducted successfully so far due to the enormous commitment of patients and clinicians to find a treatment for SMA. We believe the results due in fourth quarter 2013 could be an historic moment in the development of treatments for SMA.”

“The recommendation by the DMC to proceed confirms that olesoxime is a safe molecule and we look forward to quickly analysing results on the efficacy outcome of the trial after it reaches the planned conclusion,” said principle investigator Dr Enrico Bertini. “Other interesting potential outcomes that will surely emerge from the results of this trial will be related to the issue of biomarker analysis and also to the reliability, variability and validity of electrophysiological data which have been collected longitudinally in patients. All the information from this study will be valuable for future clinical multi-centre trials in SMA. In the meantime we hope that olesoxime will have a therapeutic impact on the natural history of SMA.”

“Thanks to the donations to the French telethon, we have been supporting the development of olesoxime since the first screening up to and including the ongoing clinical trial. This is an important clinical study and brings hope for a first potential treatment for SMA patients,” said Christian Cottet, CEO, AFM-Telethon.

“Trophos and the AFM have been working together for over a decade. This crucial clinical study is the latest step in our long standing partnership,” said Christine Placet, CEO, Trophos. “Olesoxime has a promising profile as a potential treatment for SMA. We are very hopeful that the results of this study will bring a much needed treatment option and new hope to SMA patients and their families. Trophos has a history of commitment to developing breakthrough therapies for rare and serious neurodegenerative diseases.”

Trial design and end-points

The study is a 24-month randomized, parallel group, double-blind, placebo controlled trial comparing olesoxime against placebo in non-ambulant type II and type III SMA patients aged from 3 to 25 years old. Olesoxime is administered at the dose of 10 mg/kg/day using a specially developed liquid formulation; patients were randomized to receive olesoxime in a 2:1 ratio versus placebo.

The primary end-point of the study is the change from baseline in the Motor Function Measure (MFM) functional scale. Secondary endpoints include the Hammersmith Functional Motor Scale and electromyography (CMAP -Compound Muscle Action Potential – and MUNE – Motor Unit Number) as well as measure of safety, tolerance and quality of life. Trophos is also exploring changes in a panel of possible SMA biomarkers in collaboration with the Spinal Muscular Atrophy Foundation (http://www.smafoundation.org). The study is sponsored by Trophos and the principle investigator is Dr. Enrico Bertini, a key opinion leader with extensive experience in the natural history as well as the design and performance of clinical trials in SMA. The study is being conducted in 22 centers in France, Italy, Germany, UK, Belgium, the Netherlands and Poland by a consortium of prominent European clinical investigators, all of whom have extensive experience conducting and collaborating in SMA clinical trials.

For further details, please refer to: http://www.clinicaltrials.gov/ct2/show/NCT01302600

About SMA

Spinal Muscular Atrophy is an autosomal recessive genetic disease that affects the motor neurons of the voluntary muscles that are used for activities such as crawling, walking, head and neck control and swallowing. Approximately 1 in 6,000 babies born are affected. The mutated gene responsible for SMA is carried by up to 20 million potential parents in the US and EU, most unknowingly. SMA patients are divided into four subtypes depending on disease onset and severity but all suffer from degeneration of motor neurons controlling voluntary muscles with proximal limb and trunk muscle weakness leading to respiratory distress and in the most severe cases, ultimately death.

About olesoxime

Olesoxime (TRO19622) is the lead compound in Trophos’ proprietary cholesterol-oxime family of compounds that target and preserve mitochondrial integrity and function in stressed cells. Preclinical studies have demonstrated that olesoxime promotes the function and survival of neurons and other cell types under disease-relevant stress conditions and has been shown to be active in multiple preclinical neurodegeneration models including the NSE-Cre F7/F7 model of SMA.

Orphan drug designations

Trophos has been granted ‘Orphan Medicinal Product’ designation for olesoxime for the treatment of SMA by the European Commission and orphan drug designation by the U.S. Food and Drug Administration.

About Trophos: http://www.trophos.com

Trophos is a clinical stage pharmaceutical company developing innovative therapeutics for indications with under-served needs in neurology and cardiology. The company has a novel and proprietary cholesterol-oxime based chemistry platform generating a pipeline of drug candidates. Besides the lead product, olesoxime (TRO19622), being developed for SMA, a second product, TRO40303, is in clinical development to treat reperfusion injury in patients undergoing angioplasty to treat an acute myocardial infarction; a phase II study is ongoing as part of the MitoCare project, with the support of EU FP7 funding. Trophos’ mitochondrial-targeted compounds enhance the function and survival of stressed cells by preventing mitochondrial permeability transition, a key determinant of cell death or survival. There is growing support for the therapeutic rationale for such mitochondria targeted drugs, which Trophos is uniquely placed to exploit.

Trophos was founded in 1999, is based in Marseille, France and currently has 27 employees.

About the AFM

The French Muscular Dystrophy Association (AFM) federates patients with neuromuscular diseases (genetic diseases that kill, muscle after muscle) and their parents. Thanks in great part to donations from France’s annual Telethon (EUR 94.1 million in 2011), the AFM has become a major player in biomedical research into rare diseases in France and worldwide. It is currently funding 36 clinical trials on 30 different genetic diseases affecting the eyes, the blood, the brain, the immune system, muscles and other parts. Thanks to its Généthon research lab, the AFM stands out through its unique ability to produce and test its own gene-based medicines.

More information at http://www.afm-telethon.fr/