Prothena data stimulate market tremors


In a setting where phase I Alzheimer’s disease data can be worth $6bn in market capitalisation it seems fair to assume that similarly early Parkinsons’s data are worth $258m. That must be the view of Prothena’s investors, who were enlivened by the performance of PRX002 in a dosing study.

Finding a statistically significant reduction in levels of alpha-synuclein was taken as an encouraging sign of potential benefit for patients with the degenerative disorder. This also confirmed that Roche had made a decent CNS bet when it signed global rights to this asset for $45m before it had even been tested in humans.

PRX002 yielded a mean reduction of 96% in the levels of circulating alpha-synuclein in the bloodstream, a finding that was significant at p=0.00001 in the 40-patient trial. The Prothena asset is an antibody that binds alpha-synuclein, and it is hoped that it will help slow or stop disease progression.

Alpha-synuclein is a component of the aggregations of proteins inside nerve cells called Lewy bodies that are a hallmark of this disorder. Elevated levels and abnormal forms of this protein have been associated with the neurodegeneration of Parkinson’s.

The single-ascending dose trial tested as its primary endpoint safety and tolerability by increasing patients’ exposure from 0.3mg/kg to as much as 30mg/kg. Importantly, the investigators detected no dose-limiting toxicities, nor hypersensitivity or drug-related serious adverse events. The findings have set the stage for a second phase I study, a 60-patient trial with a multiple-ascending dose design that should read out early next year.


Announcement of the results from this first dosing trial was enough to send Prothena shares up 32% to $38.66 on Friday, the company’s first trip over the $1bn market cap threshold since April 2014, when shares fell after readout of hotly awaited phase I/II amyloidosis data from its lead candidate, NEOD001.

That agent has entered a pivotal phase II/III trial that could take three years to report out, as its primary endpoint is a composite of all-cause mortality or cardiac hospitalisation. Thus for now PRX002 represents the primary driver of investor decisions, at least until news emerges on a third pipeline asset, PRX003, in psoriasis.

PRX003 will be tested first in healthy volunteers, so no early signs of efficacy are likely to materialise until next year. Thus with all catalysts some months away, it is not too surprising to see shares off as much as 5% to $36.11 in trading this morning.

Elan spin-off

Prothena had started life as a spin-out of Elan’s drug discovery laboratories, beginning with a healthy $125m in cash and building a cushion of nearly $300m through two secondary offerings and the Roche deal.

The company expects to burn up to $72m this year and end the year with around $225m in cash, which should allow it to maintain its clinical programme for some time; still, with shares at their highest level in nearly a year, it might be wise to strike while the iron is hot and top up its coffers.

Last year, Perrigo unhitched itself of the 18% stake that was a legacy of its Elan acquisition – at a modest-looking $26 per share just weeks before the amyloidosis data had read out.

Meanwhile, Roche, which has struggled in CNS in recent months, now appears to have at least a glimmer of hope in Parkinson’s. It has licensed out most of its own agents that had shown promise in this space, and aside from Prothena’s offering retains in its pipeline mostly interest in preclinical assets.

Interestingly, one is another alpha-synuclein inhibitor, ReS9-S, from the private Belgium group reMYND, although little news has been released about the project.

For all of Friday’s trading action, PRX002 is now a 2016 story. Following Prothena will require patience, and with the biotech boom being in the here and now it is not surprising to see investors turn elsewhere today.

Trial ID
Phase I single ascending dose in 40 patients NCT02095171

To contact the writer of this story email Jonathan Gardner in London at or follow @ByJonGardner on Twitter

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