Actelion AG's potential acquisition of Trophos SA is off the table, following the failure of the latter firm's lead drug olesoxime to demonstrate efficacy in a pivotal Phase III trial in amyotrophic lateral sclerosis (ALS) or Lou Gehrig's disease.

Allschwil, Switzerland-based Actelion had paid €10 million (US$13.2 million) for an option to acquire Trophos for up to €195 million, pending the outcome of the trial.

But Marseille, France-based Trophos said Tuesday that olesoxime, which acts via a neuroprotective mechanism, failed to demonstrate any improvement in survival in the 512-patient trial.

'We believe, sadly, this casts a considerable shadow on the general neuroprotective approach in ALS,' Trophos CEO Damian Marron told BioWorld Today.

The study was a high-risk undertaking from the outset, as it represented the first efficacy study of the drug in patients.

'There is not a proven Phase II methodology in ALS,' Marron said. 'That would be a great thing for the area, if there was one, but there isn't.'

The company's conclusion is the patients recruited onto the study – who had received a diagnosis between six and 36 months previously – were already too far advanced to benefit from olesoxime, given the severity of the disease and the rapidity of its progression. There can be a considerable lag between the appearance of symptoms and definitive diagnosis.

'It's a diagnosis of exclusion,' Marron said. Biomarkers and other diagnostic tools are lacking.

Olesoxime is thought to act by modulating the mitochondrial permeability transition pore (mPTP). The pore mediates the so-called mitochondrial permeability transition, a sudden rise in the permeability of the mitochondrion, which occurs in cells undergoing apoptosis.

The same drug is currently undergoing a second pivotal trial, in spinal muscular atrophy (SMA), a rare, genetically inherited neuromuscular disorder, of varying severity. The most common form of the condition is caused by mutations in the survival motor neuron protein, an RNA-binding protein involved in the assembly of small nuclear ribonucleoprotein (snRNP) complexes, which, in turn, are responsible for pre-mRNA splicing.

The outcome of the ALS study should not necessarily undermine this trial, as SMA progresses more slowly, Marron said. Interim data are expected in the fourth quarter of 2012.

The study, the primary endpoint of which is a change from baseline in a motor-function-measure scale for neuromuscular disease, will read out fully during the second half of 2013.

The same drug also has potential to treat progressive forms of multiple sclerosis (MS), Marron said. As well as its neuroprotective properties, olesoxime could also promote remyelination, as it stimulates the maturation of oligodendrocytes, the cells that produce myelin, the insulating sheath that is the target of the autoimmune attack in MS. However, the company will only proceed in that indication with a partner.

A Phase II study of TRO40303 in patients with cardiac ischemia-reperfusion injury will also read out in the second half of 2013. It, too, modulates the mPTP.

Trophos has so far raised €74 million in total funding, including €29 million from venture capital investors and €35 million in research funding from the public sector and from medical charities. The company is funded through 2013, Marron said.