Phase 1b study of olesoxime initiated in multiple sclerosis (MS) patients

Mar 14 2013

Trophos SA, a clinical stage pharmaceutical company developing innovative therapeutics for indications with under-served needs in neurology and cardiology, announced the initiation of a phase 1b study of olesoxime in multiple sclerosis (MS) patients as a complementary therapy to their treatment with interferon beta.

The clinical trial is designed to demonstrate the safety and tolerability of olesoxime as a co-medication with immunomodulatory treatments, interferon beta being the most frequent first line therapy for relapsing remitting MS. The study will also be a pilot study to assess the feasibility of various magnetic resonance imaging (MRI) procedures to detect signs of neuroprotection and/or myelin repair in a multicenter trial. The clinical trial is in preparation for future large-scale clinical trials to assess efficacy of olesoxime to prevent progressive disability in MS patients.

The trial, led by professor Jean Pelletier (AP-HM/CNRS-CRMBM/CEMEREM), will be conducted in three leading MS clinical centers in France, located in Marseille (AP-HM CHU Timone), Rennes (CHU de Rennes) and Reims (CHU de Reims). Two MRI specialist labs (UMR CNRS 7339-CRMBM/CEMEREM in Marseille and INRIA VISAGES in Rennes) will analyze the imaging biomarker data acquired in the study. This trial is the objective of an ANR-funded project, Translate MS-Repair, awarded to Trophos and this consortium (see press release October 11, 2012).

"MS is a chronic inflammatory disease leading to demyelination and axonal degeneration in the central nervous system. Today there are a number of effective treatments to control these relapsing inflammatory episodes in MS; however, they have little effect on progressive disability in MS patients," said Dr. Rebecca Pruss, Trophos' chief scientific officer. "It is also now recognized that MS is a chronic neurodegenerative disease. It affects 2.5 million people globally and is the first cause of non-traumatic disability in young adults. As a result, there is a very high unmet need for agents to promote myelin repair and prevent the neurodegeneration that underlies progressive disability in MS."

"This study is expected to provide further evidence of the safety and tolerability of olesoxime as a complementary therapy to immunomodulatory treatments used by the majority of MS patients," said Dr. Pascal Longlade, Trophos' chief medical officer. "We see this study as the first step in the development of olesoxime to prevent disability in both relapsing remitting as well as progressive forms of MS."

"MS disease progression has a market potential of over USD 1 billion. Trophos hopes that gathering leading experts in MS and bringing our consortium based approach to MS will make a real difference to this so far unmet medical need," said Christine Placet, CEO, Trophos. "Trophos remains committed to bringing solutions to conditions like MS and SMA, as well as cardiac reperfusion injury."

About Translate-MS-Repair

Translate-MS-Repair (ANR-12-RPIB-0005-01) is a two-year project aimed at the clinical translation of the results obtained in a previous ANR-funded project: MS-Repair (see below). The clinical Phase 1b study will be a randomized, placebo-controlled, double blind study to evaluate the effect of olesoxime in 42 relapsing remitting MS patients stably treated with all forms of interferon beta. The primary objective is to confirm the safety and tolerability of olesoxime in association with interferon beta. The primary outcome measure is the cumulative incidence of adverse events with the secondary outcome measures being total, new and enlarging brain lesions assessed by MRI. Besides these conventional MRI procedures, a range of non-conventional procedures will be explored including 23Na-MRI, diffusion tensor imaging, magnetization transfer imaging and magnetic resonance spectroscopy in order to assess their feasibility for use as biomarkers of neuroprotection and/or remyelination in a multicenter trial.

About Olesoxime

Olesoxime (previously known as TRO19622) is a mitochondrial targeted, cholesterol-like compound that is currently undergoing Phase II clinical evaluation for the treatment of spinal muscular atrophy. Olesoxime's safety and tolerability has already been tested in 15 clinical trials involving 968 patients or healthy volunteers and has proved to have an excellent safety profile.

The mechanism of action of olesoxime involves prevention of mitochondrial dysfunction and improved microtubule dynamics, both implicated in neuroprotection and oligodendrocyte maturation. The ANR-funded MS-Repair project (ANR-08-BIOT-016-01) showed that the molecule is not only neuroprotective, but it also promotes myelination by accelerating the maturation of oligodendrocyte progenitor cells (OPCs) into mature oligodendrocytes. These studies were reported by Trophos and consortium partners from Aix-Marseille University and CNRS, IBDML (UMR 6216) and CRMBM (UMR 6612) in Annals of Neurology (Magalon et al, Ann Neurol. 2012;71:213-26).

About Multiple Sclerosis

MS is a chronic inflammatory disease of the central nervous system leading to demyelination and axonal degeneration. When myelin is destroyed, it leaves random areas of scar tissue (sclerosis) which affect the ability of nerve cells to communicate with each other. This results in the blocking of neurological transmissions leading to physical and cognitive disability. It is estimated that approximately two million people worldwide suffer from MS. Most of them are 20 - 40 years old with females outnumbering males by 2:1 ratio. The majority of MS patients are initially diagnosed on the basis of recurring inflammatory episodes (relapsing remitting MS) but about 50 per cent of these patients will show progressive disability even in the absence of inflammatory relapses (secondary progressive MS) within 10 years of diagnosis, those figures rising to 90 per cent within 30 years. Others present with progressive neurological symptoms typical of MS without an episodic inflammatory history (primary progressive MS). Although there are several therapies approved for the treatment of RRMS, there are no marketed drugs to treat progressive MS.

About Trophos

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.