Therapeutic focus – Two steps back for Huntington’s disease


Just when pharma seemed on the verge of developing the first drug indicated for slowing the progression of Huntington’s disease, setbacks restored the status quo, and despite the current attraction of orphan diseases the industry’s pipeline remains thin.

The phase III failure two years ago of Medivation’s Dimebon was followed by a high-profile debacle over pivotal study data for Neurosearch’s Huntexil, after which the latter company has moved to wind itself up. Late-stage success seems in desperately short supply, and the most advanced project, Raptor Pharmaceutical’s Procysbi (cysteamine), is in an investigator-sponsored phase II/III trial (see table below).

The Procysbi study is at the Centre Hospitalier Universitaire d'Angers in France, and it is surprising that progress has been so slow given that cysteamine’s effect in slowing progression was documented over 20 years ago. Procysbi is better known as a potential treatment for the ultra-orphan metabolic condition nephropathic cystinosis, and this is Raptor’s near-term focus (Event – Raptor hopes to open the door to the US, April 4, 2013).

Symptomatic treatments

Huntington’s is a hereditary neurodegenerative disease caused by a genetic mutation, and affected patients typically experience cognitive deterioration, motor disorders and psychiatric disturbances. Life expectancy is 10 to 15 years from diagnosis.

There is one US-approved product – Lundbeck’s VMAT2 inhibitor Xenazine – although this is not indicated to alter disease progression. Rather, it is approved for the symptomatic treatment of the movement disorders or chorea that are associated with Huntington’s. A number of other agents are in studies for Huntingdon’s chorea, but these are excluded from this analysis.

Among potential disease-modifying projects, Dimebon was abandoned after failing phase III studies in Alzheimer’s as well as Huntington’s (Dimebon is Medivation's frustration once again, April 11, 2011). After its phase II and III foul-up Huntexil was sold to Teva for $26m under the winding-up of Neurosearch last September.

Teva now plans to start a new phase II or III trial and is sponsoring an open-label extension of Neurosearch’s failed phase II Hart study. Its other shot at the goal, laquinimod – separately filed for multiple sclerosis – should enter a phase II Huntington’s study this year.

Industry pipeline of Huntington's disease projects
Status Product Pharmacological class Company Trial ID Notes
Phase II/III Procysbi (cysteamine) Cystine-depleting agent Raptor Pharmaceutical EudraCT Number: 2010-019444-39  PhII/III trial by Centre Hospitalier Universitaire d'Angers.
Phase II Huntexil (pridopidine) Dopaminergic stabiliser Teva Pharmaceutical Industries Failed phase II and III. New phase II study in preparation.
Selisistat Sirtuin (SIRT1) inhibitor Siena Biotech NCT01521585 144-patient study completed; no results yet available.
PBT2 Tau aggregation inhibitor Prana Biotechnology NCT01590888 Recruitment completed in Dec 2012.
Phase I Laquinimod Immunomodulator Teva Pharmaceutical Industries/Active Biotech Phase II due to start in 2013.
GSK356278 Phosphodiesterase IV inhibitor GlaxoSmithKline NCT01573819  Phase I completed in 2012.
NP03 Low-dose lithium formulation Medesis Pharma Phase II/III study is in preparation with Sainte-Justine University Hospital Center Research Center. 
EVP-0334 Histone deacetylase inhibitor MethylGene/EnVivo Pharmaceuticals 2005 research collaboration. EnVivo has completed Phase I.

Given the relatively early stage of the industry pipeline there is little in the way of consensus data to go on as far as valuing any of the projects.

Procysbi is expected to generate just 15% of its 2018 sales of $195m in Huntingdon’s, according to EvaluatePharma’s sales by indication module. No forecasts are available for either of the phase II projects – Siena Biotech’s selisistat and Prana Biotechnology’s PBT2. In comparison Xenazine sold $274m last year, but is set to lose patent expiry in August 2015.

It is notable how relatively little big pharma involvement there is in Huntington’s, although this might be explained by the disease being an orphan condition, meaning that a large sales force should not be needed to sell any approved drug.

But it is noteworthy that big pharma’s interest in rare diseases is growing, and the impression that industry majors have given up on Huntington’s will not help progress. For the time being Huntington’s looks set to keep its reputation as a notoriously intractable disease.

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

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