Trophos, a clinical stage pharmaceutical company developing innovative therapeutics for indications with under-served needs in neurology and cardiology, has announced top-line results from a pivotal clinical trial of its lead product candidate olesoxime in spinal muscular atrophy (SMA) show a beneficial effect on the maintenance of motor function in SMA patients. If approved, olesoxime could be the first treatment specifically developed for SMA patients.
 
SMA 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. SMA affects approximately 20,000 people worldwide. One in every 6,000 babies is born with SMA. It is the number one genetic cause of death in children under the age of two.
 
The mutated gene responsible for SMA is carried by up to 20 million potential parents in the US and EU. Most of them are unaware that they are carriers. SMA patients are divided into four subtypes depending on disease onset and severity, but they all suffer from the degeneration of motor neurons controlling voluntary muscles, with proximal limb and trunk muscle weakness leading to respiratory distress and in the most severe cases, death.
 
The pivotal study was conducted in seven European countries. It was a double-blind, placebo-controlled study in 165 type II and non-ambulatory type III SMA patients, ranging in age from 3 to 25 years old. Patients were randomized to treatment (10 mg/kg olesoxime dosed daily as a liquid oral suspension or matching placebo in a 2:1 ratio). They were evaluated every three months for two years. The primary outcome measure was the change in motor function at two years using a standardized neuromuscular disease-specific functional scale, the MFM. The secondary outcome measures included an additional scale, the Hammersmith Functional Motor Scale for Spinal Muscular Atrophy, as well as electromyography measures, pulmonary function, patient-reported outcomes such as clinical global impression (CGI), quality of life measures (PedsQL), typical SMA complications and product safety.
 
Results from this pivotal study showed a progressive loss of motor function in the placebo arm, as described for the typical disease progression and similarly documented in other observational and interventional trials. This loss of function, assessed as the primary endpoint, was prevented for two years in olesoxime-treated patients, with fewer disease-related adverse events. Other secondary endpoints were consistent with these effects. Detailed results will be published and presented at upcoming conferences in Europe and the USA. The discovery of olesoxime and its development for SMA was mainly supported by AFM-Telethon, the French muscular dystrophy association.
 
“Spinal muscular atrophy is a devastating condition and a leading cause of death in babies and infants under two years old. Children with a less severe form of SMA suffer progressive muscle wasting and loss of mobility and motor function,” said Dr. Enrico Bertini, the principle investigator of the study. “Olesoxime has the potential to be the first ever approved treatment specifically developed for SMA patients. Its neuroprotective effect combined with fewer adverse events caused by the disease itself is encouraging. The results and data collected in this study on outcome measures and biomarkers will establish standards for future clinical trials in SMA patients.”
 
“We are grateful for the long-term financial support and commitment of AFM-Telethon and our other shareholders, to the patients, to their families and clinicians who have enabled us to complete this pivotal trial with olesoxime,” said Christine Placet, chief executive officer of Trophos. “Our focus now is on the regulatory steps needed to bring this important product to patients as quickly as possible. We are currently exploring a number of options, including potential industry partnerships and identifying new sources of funding.”

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.