Therapeutic focus – ALS in desperate need of success stories


News this week that Teva’s talampanel failed to meet its efficacy endpoints in a phase II trial in patients with amyotrophic lateral sclerosis (ALS) is further evidence, if any were needed, of the major developmental pitfalls inherent in this major unmet medical need.

The only FDA approved drug for ALS, riluzole, offers only a modest increase in average survival time, which currently is just three to five years. Similar to many neurodegenerative disorders, a genuine disease-modifying therapeutic agent is desperately needed for patients with ALS, estimated to affect 50,000 people worldwide. Teva’s setback now throws the spotlight on a particularly thin-looking late stage pipeline of products for ALS, just two in phase III and five in phase II (see tables below).

Limited options

ALS, also referred to as Lou Gehrig's disease, is a form of motor neuron disease which causes muscle weakness and atrophy throughout the body as upper and lower motor neurons degenerate over time.

Mean survival time with ALS is three to five years, although many people can live ten or more years. In some cases disease progression actually stops, although the reasons why are still not understood; gaining further insight into the mechanisms underlying the illness is therefore crucial to developing new therapies.

Riluzole, discovered and initially developed by Rhône-Poulenc, was approved in 1995 and remains the main treatment option for ALS. The drug works by blocking the activity of glutamate, a neurotransmitter believed to play an important role in the development of ALS.

Sold globally as Rilutek by Aventis and now Sanofi-Aventis, sales of the drug peaked in 2006 at $182m. Since then Sanofi has stopped disclosing sales and analysts have dropped product forecasts from their models.

Thin pipeline

In terms of the overall pipeline, data from EvaluatePharma reveals just 51 products are in active development globally for ALS, a further 21 having hit the rails along the way.

Count of ALS products
Status Count
Marketed 1
Phase III 2
Phase II 6
Phase I 14
Pre-clinical 21
Research project 8
Abandoned - Phase III 6
Abandoned - Phase II 5
Abandoned - other 10
Total 73

In terms of the late stage pipeline, the table below highlights the key products entering a pivotal stage in development.

Mitsubishi Tanabe Pharma has completed phase III trials in ALS of its stroke drug, Radicut (edaravone), although the timing of the release of results remains unclear.

Technically a phase II/III trial of CytRx’s arimoclomol remains ongoing, expected to complete by the end of 2012. However, the FDA placed a clinical hold on the trial last year and the company is currently seeking a partner for the product or may decide to spin it out into a separate entity.

Meanwhile back in phase II, a number of important trials are due to complete this year. According to, trials of Namenda, CK-2017357 and SB-509 in ALS will conclude this year.

CK-2017357 is one of Cytokinetics’ lead pipeline candidates and the company recently reported rapid recruitment in its phase IIa trial which started in April and will complete in August.

Knopp Neurosciences has so far revealed encouraging phase II data for KNS-760704 (dexpramipexole) in ALS and intends to start a phase III trial by the end of 2010, although at this stage it is unclear whether the private company has the funding in place to do so or is seeking a partner.

Which leads nicely on to the particularly quiet partnering scene for ALS products. Just 17 licensing deals have been signed in the last decade for products in development for ALS and aside from Sanofi’s involvement in Rilutek, big pharma is conspicuous by its absence from the field. Most of the pipeline candidates are being developed by small biotechs and remain unpartnered.

Only GlaxoSmithKline and Roche are involved in developing ALS candidates, currently undergoing phase I trials. As such, the disease needs some success stories to bring hope to ALS patients and pique the interest of bigger pharma partners.

Approved and late stage pipeline of products for amyotrophic lateral sclerosis (ALS)
Status Product Company Pharmacological Class Indication Summary
Marketed Rilutek (riluzole) Sanofi-Aventis Glutamate release inhibitor ALS [Marketed]
Phase III Radicut (edaravone) Mitsubishi Tanabe Pharma Free radical scavenger Stroke, acute [Marketed]; ALS [Phase III]
Arimoclomol CytRx Superoxide dismutase (SOD1) chaperone ALS [Phase III]; Stroke prophylaxis [Pre-clinical]
Phase II Namenda (memantine) Forest Laboratories/Merz NMDA antagonist Alzheimer's disease [Marketed]; Dementia, senile [Marketed]; Pain, post-operative [Marketed]; ALS [Phase II]
CK-2017357 Cytokinetics Musculoskeletal agent ALS [Phase II]; Age-related frailty [Phase I]; Cachexia (wasting) [Phase I]
KNS-760704 (dexpramipexole) Knopp Neurosciences Dopamine D3 agonist ALS [Phase II]
SB-509 Sangamo BioSciences VEGF activator Diabetic neuropathy [Phase II]; ALS [Phase II]
sNN0029 NeuroNova VEGF activator ALS [Phase II]
Talampanel (talampanide) Teva Pharmaceutical Industries AMPA antagonist Glioblastoma multiforme [Phase II]; ALS [Abandoned - Phase II]

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