Clinical Trials

* On April 28, 2014, Trophos and AFM-Telethon (The French Muscular Dystrophy Association) have announced that data from the pivotal clinical trial of olesoxime in spinal muscular atrophy (SMA) will be presented during the 66th American Academy of Neurology (AAN) annual meeting to be held in Philadelphia, PA, USA, from April 26 to May 3 2014. The data shows that patients treated with olesoxime were able to maintain motor function over the two-year period of the study and that typical health complications associated with SMA occurred less frequently than in patients treated with a placebo, leading to better well being. The new data presented at AAN is from the recently completed international, double-blind, placebo-controlled study involving 165 type II and non-ambulatory type III SMA patients, ranging in age from 3 to 25 years old. The results show that olesoxime treatment preserved motor function for two years using the Motor Function Measure scale (MFM) D1+D2 as the primary endpoint. The MFM is a standardized neuromuscular disease-specific functional scale. In contrast, patients in the placebo arm of the study experienced a loss of motor function starting from a mean score of 39 per cent at baseline to 37.1 per cent after two years. The mean loss of 1.9 points in motor function over the two-year study period confirms that the natural disease progression results in approximately 1 per cent per year loss of motor function in SMA patients. The difference in favor of olesoxime at 24 months is statistically significant (p equals 0.038) while the overall treatment effect on motor function measured at four visits during the study was highly significant (p equals 0.0045). Interestingly, the effect of olesoxime could be detected even within six months following initiation of treatment. The results observed in olesoxime treated patients are consistent with the working hypothesis set up when designing the study. On top of this statistically significant result on the primary endpoint, motor function was also measured with the Hammersmith Functional Motor Scale (HFMS) as a secondary endpoint. HFMS changes over a 21-month period showed a similar positive trend and a significant effect of olesoxime when comparing response rates (i.e. the percentage of patients who maintained function during the trial), with 48 per cent in the olesoxime arm versus only 28 per cent in the placebo arm (p equals 0.015). Data analyses considering age, gender, SMA type or country as covariates show these variables have no influence on the results.

The safety of olesoxime was confirmed in the study. Moreover, even though the trial was not designed to address the point, data related to typical SMA complications showed a clear improvement and less frequent disease-associated events such as lower respiratory tract infection or spine surgery to treat scoliosis in patients treated with olesoxime.

* On March 10, 2014, Trophos has announced that top-line results from a pivotal clinical trial of olesoxime in spinal muscular atrophy (SMA) show a beneficial effect on the maintenance of motor function in SMA patients.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. “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.” If approved, olesoxime could be the first treatment specifically developed for SMA patients.

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 FDA.

* On November 5, 2013, Trophos, 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 spinal muscular atrophy. 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 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. Trophos is now in discussions with both the EMA and the FDA to prepare for the next steps in bringing olexosime to market as soon as possible.

* On February 27, 2013, Trophos has announced  the completion of the interim analysis of the pivotal efficacy study of olesoxime in spinal muscular atrophy. 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. 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.

* On September 8, 2011, Trophos has announced that it has completed patient enrollment for the pivotal efficacy study of olesoxime in spinal muscular atrophy. Over 160 patients have been recruited since the start of the study in October 2010. Efficacy results are expected in the second half of 2013.

* On April 15, 2011, Trophos has described the design of its pivotal clinical study of olesoxime in spinal muscular atrophy (SMA) via a poster presentation at this week’s 6th Annual American Academy of Neurology (AAN) meeting held in Honolulu, Hawaii, US, April 9 to 16, 2011. The poster, on the pivotal efficacy study of olesoxime in the rare, neurodegenerative condition, SMA, demonstrates how the challenges of designing a robust study in an indication where there is no precedent were met by bringing together and working with key opinion leaders, patient and physician networks and regulators. The study commenced in October 2010 and is currently recruiting patients. Efficacy results are expected in the second half of 2013.