Trophos announces results of phase III study of olesoxime in Amyotrophic Lateral Sclerosis
Marseille, France – December 13, 2011 - Trophos SA
announces today the results from the phase III study of
Trophos’ lead compound, olesoxime, in 512 patients with ALS.
Olesoxime did not demonstrate a significant increase in survival
versus placebo in patients receiving riluzole (Rilutek(R)). A trend
was seen on patients’ function as measured by the ALSFRS-R
functional rating scale. Olesoxime was very well tolerated.
Following receipt of these results, Actelion has informed Trophos
of its decision to not exercise its exclusive option under the July
2010 acquisition option agreement between Trophos and Actelion (see
Actelion release of 13 December 2011).
Trophos continues its ongoing programs and has financing secured to
at least the end of 2013. These programs include:
· An ongoing pivotal trial of olesoxime in Spinal
Muscular Atrophy (SMA) with results due in the second half of
2013,
· An ongoing phase IIa proof-of-concept study of TRO40303 in
cardiac ischemia-reperfusion injury (IRI), with results due before
end 2012,
· A planned phase II proof-of-concept trial of olesoxime in
Multiple Sclerosis (MS) disease progression (subject to securing
outside funding),
· A research collaboration with Actelion to screen and
characterize Actelion compounds using Trophos’ proprietary
CNS assay technology.
The inability of olesoxime to show a greater effect on survival for
ALS patients above that of riluzole in the phase III trial is most
likely because the disease process is already so severe and rapidly
progressing by the time of diagnosis that any further benefit of
olesoxime over that of riluzole cannot be detected. Indeed, it is
known that in the most widely used ALS model, over 50 per cent of
the motor neurons and neuromuscular connections have already been
lost by the time the first symptoms appear. Of Trophos’ other
target indications for olesoxime, SMA type II and III, being
studied in an ongoing trial, these differ in that disease
progresses slowly over many years. Progressive MS is again
different as neuronal degeneration correlated with disease
progression only sets in after symptoms appear.
“The results of this study in ALS are disappointing, above
all for the ALS community, who urgently require new therapies that
can prolong survival and improve function. We are genuinely proud
to have worked closely with this community and our international
partners in the MitoTarget project on this important and very well
run study,” said Damian Marron, CEO, Trophos. “We
remain convinced of the promise of our cholesterol-oxime,
mitochondrial pore modulator compounds. We have ensured that
Trophos is financed until at least the end of 2013, so that we
continue to move forward on our other programs, which address high
medical need orphan or niche indications with no existing
treatments.”
Details of the study
The study was an 18-month randomized, parallel group, double-blind,
placebo-controlled trial evaluating the efficacy and safety of
olesoxime against placebo in patients treated with riluzole. The
study was conducted in 512 patients diagnosed with ALS between six
and thirty six months before enrolment and receiving standard care.
Olesoxime was dosed orally at 330 mg once-a-day.
Olesoxime did not demonstrate significant benefit on the primary
endpoint of survival after 18 months of treatment over that of
riluzole. A trend was seen on the secondary criteria of ALSFRS-R on
a pre-specified analysis after nine months of treatment. Olesoxime
was very well tolerated with a side effect profile similar to
riluzole plus placebo. Full results will be published in scientific
journals and congresses in due course.
The study was undertaken in 15 centers in France, Germany, UK,
Belgium and Spain as part of a three-year collaborative project
named MitoTarget (Grant Agreement No: HEALTH-F2-2008-223388) for
which the European Commission has awarded a grant of nearly EUR six
million.
About Olesoxime
Olesoxime is Trophos’ lead compound of a proprietary
mitochondrial pore modulator series. 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).
Olesoxime is in an ongoing pivotal efficacy and safety study in
Spinal Muscular Atrophy (SMA), substantially funded by the AFM
patient association (see Trophos release of October 15, 2010), with
results due in the second half of 2013. Olesoxime is also at entry
to phase II development for multiple sclerosis.
About TRO40303 and cardiac ischemia-reperfusion injury
Use of thrombolytics and balloon angioplasty to rapidly reperfuse
heart tissue with oxygen following an MI has greatly reduced
morbidity and mortality. Paradoxically, about 50 per cent of the
damage to heart tissue following MI is due to re-oxygenation
leading to a burst of reactive oxygen species as energy production
by mitochondria is reactivated. The mechanism of action of TRO40303
involves prevention of stress-induced mitochondrial permeability
transition, a target implicated in cardiac reperfusion injury. In a
model of MI, treatment with TRO40303 at the time of reperfusion was
shown to significantly reduce infarct size. This innovative program
was supported by a grant of nearly EUR one million by the French
Agence Nationale pour la Recherche (ANR) in a project named
IRIstop, (see release of February 28, 2008).
TRO40303 has successfully completed a phase I study to assess
the safety, tolerability and pharmacokinetics of single escalating
doses of TRO40303 as an intravenous infusion at different rates
compared with placebo in 72 healthy volunteers. The results
demonstrated that TRO40303 can be safely administered by the iv
route in humans at doses expected to be pharmacologically active.
Full results of this study were recently presented at the European
Society of Cardiology 2011 held in Paris from 27th-31st August
(Schaller et al., ESC 2011 Paris, N88427, Phase I clinical trial of
TRO40303, a new mPTP inhibitor for reducing reperfusion
injury).
The ongoing phase II study of TRO40303 is part of a collaborative
project named MitoCare (Grant Agreement Number:
Health-2010-261034). The European Commission has awarded a grant of
EUR six million to MitoCare, a 2.5 year international,
translational medicine project led by Trophos.
About Trophos SA – 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. The lead product, olesoxime (TRO19622), is in a
pivotal clinical study for Spinal Muscular Atrophy (substantially
funded by the AFM patient association). A second product, TRO40303,
is in phase II 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 was founded in 1999, is based in Marseille, France and
currently has 37 employees.
Juliette dos Santos
ANDREW LLOYD & ASSOCIATES
http://www.ala.com
juliette@ala.com
55 rue Boissonade 75014 PARIS FRANCE
Tel : +33 1 56 54 07 00 Fax : +33 1 56 54 07 01
Brighton Business Centre 95 Ditchling Road Brighton BN 1 4ST
ENGLAND
Tel : +44 1273 675100 Fax : +44 1273 675400
Posted: December 2011
