Trophos Completes Patient Enrolment in Pivotal Efficacy Study of Olesoxime in Spinal Muscular Atrophy
"The completion of recruitment in this pivotal clinical study in only ten months given the rarity of SMA is a great achievement and a major step in the development of olesoxime as a potential treatment for SMA," said Jean-Louis Abitbol, chief medical officer at Trophos. "SMA is a debilitating and disabling neuromuscular disease and there is a critical need for a treatment that can slow down or prevent the loss of muscle function in SMA patients, for whom no specific treatment exists today. Over 160 patients have been included in the study in only ten months, which reflects both the great commitment of patients and clinicians to find a treatment for SMA and the motivation and hard work of all involved. We anticipate the results of the trial in the second half of 2013 and hope this will be a historic moment for the medical community as well as those affected now and in the future.”
"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 phases. The recruitment in this important clinical study has just been completed with great efficiency and brings hope for a first potential treatment to SMA patients,” said Christian Cottet, CEO, AFM.
“Trophos and the AFM been working together for over a decade and this crucial clinical study with Trophos’ olesoxime in SMA is the fruit of our long standing partnership,” said Damian Marron, CEO, Trophos. ”Olesoxime has a promising profile as a potential treatment for SMA and we are hopeful the results of this study will demonstrate that promise, bringing a much needed treatment option and new hope to SMA patients and their families. This study as well as our soon to be completed pivotal study of olesoxime in amyotrophic lateral sclerosis (ALS) underlines Trophos’ commitment to developing breakthrough therapies for rare and serious neurodegenerative diseases.”
Trial design and end-points
The study is an 24-month randomized, parallel group, double-blind, placebo controlled trial comparing olesoxime against placebo in non-ambulant SMA patients aged from three to twenty five years old. Olesoxime is being dosed at ten mg/kg/day and patients are randomised to receive olesoxime in a 2:1 ratio versus placebo. The study is being conducted in over 160 patients in 24 centres in France, Italy, Germany, UK, Belgium, the Netherlands and Poland.
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 scale and electromyography (CMAP -Compound Muscle Action Potential – and MUNE – Motor Unit Number). There will be an interim analysis for efficacy and futility after one year. Safety and tolerability will be closely monitored and an independent data safety monitoring board will oversee the trial.
The study is sponsored by Trophos and is being performed by a consortium of prominent European clinical investigators, all of whom have extensive prior experience conducting and collaborating in large multi-centre clinical trials in 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 one in six thousand babies born are affected and the gene 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. (For further information, see
Olesoxime (TRO19622) is the lead compound of the Trophos' proprietary cholesterol-oxime compound family of mitochondrial pore modulators. Preclinical studies have demonstrated that olesoxime promotes the function and survival of neurons and other cell types under disease-relevant stress conditions through interactions with the mitochondrial permeability transition pore (mPTP) and olesoxime has been shown to be active in the NSE-Cre F7/F7 model of SMA.
Olesoxime is also currently undergoing a pivotal efficacy study in another rare motor neuron disease, Amyotrophic Lateral Sclerosis (ALS), which has recruited 512 patients and for which results are expected in Q4 2011. Olesoxime has successfully completed a phase 1b study in SMA patients, having previously completed phase I/Ib studies in healthy volunteers and ALS patients. These clinical trials demonstrated that the product is well-tolerated and has an excellent safety profile. They also showed that once-a-day oral dosing achieves the predicted exposure level required for efficacy, based on preclinical models.
Orphan drug designations
Trophos has been granted orphan drug designation for olesoxime for the treatment of SMA and ALS by the U.S. Food and Drug Administration and 'Orphan Medicinal Product' designation for both ALS and SMA by the European Commission in the EU.
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. The lead product, olesoxime (TRO19622), is in phase three development for the orphan neurological diseases of ALS (as part an EU funded project, MitoTarget) and spinal muscular atrophy (substantially funded by the AFM patient association). A second product, TRO40303, is in early clinical development to treat cardiac reperfusion injury (as part of an EU funded project, MitoCare). Trophos' mitochondrial pore modulator compounds enhance the function and survival of stressed cells via modulation of dysfunctional mitochondria through interactions at the permeability transition pore (mPTP). Recently published clinical studies support the therapeutic rationale for mitochondria targeted drugs, which Trophos is uniquely placed to exploit.
Trophos has two strategic partnership agreements with Actelion; an acquisition option agreement and a research collaboration agreement.
Trophos was founded in 1999, is based in Marseille, France and currently has 37 employees.
The French Muscular Dystrophy Association (AFM) carries out research programs to treat patients with neuromuscular diseases (genetic diseases that kill muscles after muscles) and supports patients and their families. Thanks in great part to donations from France's annual telethon (EUR 90 million in 2010), 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 31 different genetic diseases affecting the eyes, the blood, the brain, the immune system, the muscle... Thanks to its Généthon research lab, the AFM stands out through its unique ability to produce and trial its own gene-based medicines.
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