Roche muscles into the lead in rare wasting disease

Roche’s tie-up with PTC Therapeutics marked big pharma’s first licensing foray into spinal muscular atrophy, and today the Swiss group stamped its lead on the field by buying Trophos, holder of the industry’s most advanced SMA asset, olesoxime.

Through the move Roche has thrown down the gauntlet to Isis Pharmaceuticals, whose antisense SMA project entered phase III last year. Whether the Swiss group can consolidate its lead will now depend on its ability to file olesoxime and get it approved on the positive phase II/III data revealed last year.

The study’s readout likely triggered the takeover, even if Trophos at the time had strangely played it down (A low-key breakthrough in spinal muscular atrophy, March 14, 2014). Olesoxime showed a statistically significant improvement in the MFM scale, which Trophos said was a measure of motor function accepted by US and EU regulators.

Under today’s deal Roche will buy the private French group for €120m ($138m) in cash, followed by up to €350m in undisclosed milestone payments. The Swiss group did not reveal a filing timeline, but said it would proceed quickly, and called the Trophos study pivotal.

Big pharma buys in

Roche’s 2011 partnership with PTC has given rise to RG7800, a survival of motor neuron 2 gene splicing modifier that is now in a phase I/II study. Other large company deals have followed.

For instance, three years ago Biogen Idec picked up an option over a formal licensing alliance with Isis, which can be exercised before completion of phase II/III. In January 2013 Pfizer licensed RG3039, an early-stage project, from Repligen.

Novartis’s BVS857, in phase II for spinal and bulbar muscular atrophy, is the result of a research project with the SMA Foundation. And Roche also has a stake in a third candidate, chariSMA – a gene therapy owned by the private US group Avexis; Roche’s venture arm co-led Avexis’s $10m financing round last week.

What could differentiate some of the players is the stage of SMA that they are targeting. The rare condition results from a defect in the SMN1 gene, leading to spinal motor neurone degeneration and muscle wasting.

Type I, also called Werdnig-Hoffmann disease, is the most severe, emerging within the first six months of life; type II patients cannot walk; type IIIs can, but often become non-ambulant later in life; the relatively infrequent type IV is the least severe, occurring in adulthood.

Trophos had focused on type II and non-ambulant type III patients, which together account for some 80% of SMA cases. Avexis’s chariSMA gene therapy is in a phase I trial in type I disease, while the phase I/II study of Roche/PTC’s RG7800 only specifies people between two and 55 years of age.

Isis, meanwhile, is running two separate phase III studies with ISIS-SMNRx: one in type Is, measuring time to death or ventilation as its primary endpoint, and another, in later-onset patients, looking at change in Hammerstein motor scale – an endpoint that Trophos said olesoxime has also aced in its phase II/III study.

The private French group had raised €29m in equity since being founded in 1999, in addition to €20m of research grants, a €4m French government grant and €56m in other unspecified funds. Roche’s €120m thus looks like a reasonable, though not extraordinary, return for its venture backers.

Actelion had signed an option to buy Trophos for €125-195m in 2010, but pulled out when olesoxime failed in amyotrophic lateral sclerosis. Thanks to SMA the French company has managed to attract a similar price tag.

To contact the writer of this story email Jacob Plieth in London at [email protected] or follow @JacobEPVantage on Twitter