Trophos SA, a clinical stage pharmaceutical company developing innovative therapeutics from discovery to clinical validation for indications with under-served needs in neurology and cardiology, has completed its efficacy study of olesoxime in the rare neurodegenerative condition Spinal Muscular Atrophy (SMA).
Outcome data are expected to be available towards the end of 2013. If positive, Trophos will file olesoxime for market authorization in the EU and the US for the treatment of SMA with the aim of having the drug on the market by 2015.
The phase II/III pivotal study evaluated the efficacy and safety of Trophos’ olesoxime – a novel mitochondria pore modulator with neuroprotective and nerve repair properties. Substantial funding for this study came via the partnership of Trophos with the Association Francaise contre les Myopathies (AFM-Telethon) (see press release of March 19, 2009).
The study enrolled 165 SMA patients in a 24-month randomized, parallel group, double-blind, placebo controlled trial comparing olesoxime against placebo in type II and non-ambulant type III SMA patients aged from three to twenty five 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. This trial protocol and its data analysis plan went through the EMA protocol advice procedure.
The primary end-point of the study is the change from baseline in the Motor Function Measure (MFM) functional scale. Secondary end-points include the Hammersmith Functional Motor Scale, the respiratory function and electromyography (CMAP – Compound Muscle Action Potential and MUNE – Motor Unit Number) as well as measures 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. The coordinating investigator is Dr. Enrico Bertini, a leading clinical expert with extensive knowledge on the pathophysiology of SMA. His expertise in the design and performance of clinical trials in SMA was vital for setting up the project. The study was conducted in 22 centers in France, Italy, Germany, UK, Belgium, the Netherlands and Poland by a network of investigators with extensive experience in treating SMA patients.
“This study will be a landmark for the SMA community. Olesoxime is a promising therapy for patients living with SMA. It gives hope that they will maintain function and autonomy,” said Dr Enrico Bertini. “The longitudinal data collected from 165 patients for two years comparing functional outcome measures with potentially predictive and innovative biomarkers will make a valuable contribution to future clinical trial designs for SMA or other neuromuscular diseases.”
“We are pleased to have been able to enrol 165 patients with this rare disease according to protocol within one year, without substantial withdrawal throughout the two year clinical trial,” said Dr Wilfried Hauke, chief medical officer at Trophos. “As this was basically a clinical trial in children as young as three years old and adolescents, the exceptional motivation and commitment of the patients and their families as well as the 22 clinical teams was a key element in the successful completion of this clinical trial. We anticipate the results very shortly.”
“The partnership between Trophos and the AFM-Telethon that started in 2000 has realized a major step towards providing a possible therapy to improve the quality of life of SMA patients,” said Christian Cottet, CEO, AFM-Telethon. “This has been achieved thanks to the generous public donations that allow the AFM-Telethon to play an essential role in enabling companies like Trophos to discover and develop therapies for rare diseases.”
“Trophos and the AFM-Telethon 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. “Assuming positive results in this clinical trial, Trophos is now in discussions with both the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA) to prepare for the next steps in bringing this drug to market as soon as possible.”
Spinal Muscular Atrophy is an autosomal recessive genetic disease that affects the motor neurons of the voluntary muscles 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 ultimately, in the most severe cases, to death.
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. It has been shown to be active in multiple preclinical neurodegeneration models including the NSE-Cre F7/F7 model of SMA.
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 US Food and Drug Administration.
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 and multiple sclerosis (see press release August 6, 2013), 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 – results are expected by year end (see press release October 2, 2013). 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 16 employees.
About the AFM-Telethon
The French Muscular Dystrophy Association (AFM) brings together patients with neuromuscular diseases (genetic diseases where one muscle after another largely degrade and subsequently loose their function) and their parents. Thanks in great part to donations from France’s annual telethon (EUR 88.2 million in 2012), the AFM has become a major player in biomedical research into rare diseases worldwide. It is currently funding 34 clinical trials on different genetic diseases affecting the eyes, the blood, the brain, the immune system, muscles and other parts. The AFM stands out through its unique ability to produce and test its own innovative therapies (gene therapy and cell therapy). This is thanks to its Institut des Biotherapies for rare diseases and its production unit Genethon Bio Prod.
More information is available at http://www.afm-telethon.com