Trophos announces positive interim review in pivotal study of olesoxime in Spinal Muscular Atrophy
Topline results expected in the fourth quarter of 2013
Marseille, France, February 27, 2013 - 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. (For further information, see
http://amyotrophies-spinales.blogs.afm-telethon.fr
<http://amyotrophies-spinales.blogs.afm-telethon.fr/>,
http://www.afm-telethon.fr/disease/amyotrophie-spinale-proximale-smn1
or http://www.curesma.org)
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/
Mark Tidmarsh
ANDREW LLOYD & ASSOCIATES
http://www.ala.com
mark@ala.com
For media enquiries, please contact:
Andrew Lloyd & Associates
Neil Hunter / Juliette dos Santos
Tel: +44 1273 675100
neil@ala.com / juliette@ala.com
Posted: February 2013
