Cytokinetics sees its second miss in a year as ALS drug fails


“Benefit-ALS” has turned out to be rather a misnomer. The phase II trial of Cytokinetics’ troponin activator tirasemtiv failed to show an improvement in symptoms of amyotrophic lateral sclerosis, knocking the company’s share price by 65%.

As is usual in this type of situation, Cytokinetics says it is analysing the data to try to find a path forward. But ALS is a development nightmare. Only one compound is approved by the FDA and the disorder has seen some high-profile failures, notably Biogen Idec’s dexpramipexole last year. Cytokinetics is unlikely to be able to resurrect tirasemtiv, and after its heart failure drug omecamtiv mecarbil missed a trial endpoint last year the company is in real trouble.

Biggest seller

As with dexpramipexole before it, tirasemtiv had been given every advantage, with the FDA bestowing both orphan drug designation and fast track status. Its failure is disappointing not least because the bar was so low. Sanofi’s Rilutek, the only drug the FDA has approved for ALS, confers a survival benefit of two to three months but does not improve symptoms.

With a mechanism that affects muscle rather than nerve cells, tirasemtiv had been intended as a palliative rather than a life-extending treatment. Chances of tirasemtiv showing a better survival improvement than Rilutek – or any survival benefit at all – are slim. It has missed the only endpoint that really matters.

The Benefit-ALS trial had already suffered a nasty setback when it emerged last July that 58 patients initially treated with tirasemtiv had gone on to received placebo instead by mistake. Attributing the error to computer programming, the company had to swallow $5m in increased trial costs as more patients were recruited and the trial extended by three months.

Cytokinetics has one thing going for it: it raised some cash at just the right moment. The group completed a $37m equity financing in February. Before Benefit-ALS was known to have failed, Piper Jaffray analysts said that Cytokinetics would next need to raise capital next in 2016; if the programme has to be shuttered this could be pushed further down the line.

The company does not have much else on which to spend its cash reserves of around $119m. Other than omecamtiv, still limping on after its own setback, Cytokinetics’ other phase II projects are ispinesib and SB-743921, kinesin spindle protein inhibitors both in development for blood cancers and solid tumours (ESC – Heart failure miss knocks wind from Cytokinetics, September 3, 2013).

None of these can make up for the loss of what was forecast to be the biggest-selling drug in ALS, with predicted sales of $575m in 2018.


Optimism still exists in the ALS field, though, with BrainStorm Cell Therapeutics announcing this morning that it is kicking off a new phase II trial of its NurOwn adult stem cell technology. The BCT-001-US study will enrol 48 patients and has safety as the primary endpoint. Symptomatic improvement is a secondary endpoint. While stem cell technologies have disappointed in many arenas, it almost seems reasonable to conclude that this approach stands as good a chance in ALS as anything else.

Detailed results from Cytokinetics’ trial will be presented tomorrow at the American Academy of Neurology’s meeting. It is hard to see what they could contain that could keep this project alive.

Trial name Trial ID
Benefit-ALS NCT01709149
BCT-001-US  NCT02017912

To contact the writer of this story email Elizabeth Cairns in London at or follow @LizEPVantage on Twitter

Share This Article