Lessons learnt in the past year…update on clinical trials

Looking for a treatment for MND is the ultimate goal of the whole MND community. Unfortunately, as MND is a very complicated disease, it is not as easy as it may sound. Setting aside the sheer cost of running trials, researchers have to look at all the possible causes of MND (the genes, lifestyle and environment) and then target these with specific compounds and hoping that this strategy won’t be halted by a different biological process. This is made even harder by the large number of possible combinations of these causative factors and the many different ways these can interact.

Thankfully, lots of research groups across the world are doing their best to tackle the adverse disease mechanisms, which is why we heard lots of results of early as well as late stage clinical trials, new strategies to design better treatments in the future, and lessons learnt from previous studies.

While there was much more to hear and read at the Symposium, here we summarise the Clinical trials session (4B), where five presenters reported results and analyses of the treatments they have been investigating.


Prof Jesus S Mora, a director of the ALS Unit at Hospital San Rafael Madrid in Spain, talked us through their up-to-date findings on the efficacy of the drug masitinib, developed by AB Science.

Their latest Phase 2/3 trial showed that, when given masitinib at 4.5mg/kg/day (as opposed to a lower dose or placebo) to people with a normal progression rate (1.1 ALSFRS points or less per month), there was a 25% delay in progression of the disease, and slower decline of ALSFRS score (by 27%). The beneficial effect was also accentuated the earlier the treatment was initiated.

Masitinib is currently under investigation by the European Medicine Agency (EMA). Further confirmatory clinical trials will be conducted to provide more necessary information (including higher dosage effects) to the EMA.

Tirasemtiv – VITALITY-ALS

Further to the press release by Cytokinetics in late November 2017, announcing negative results of the drug tirasemtiv, Dr Jeremy Shefner (Barrow Neurological Institute, USA) talked us through the Phase 3 trial ‘VITALITY-ALS’.

Following up from a smaller trial, where a significant change in slow vital capacity (SVC) was seen in people taking the drug, compared to those taking placebo, VITALITY-ALS looked at the effect of various doses of tirasemtiv in over 500 participants.

Unfortunately, the drug was not well tolerated in people taking higher doses, which resulted in a large amount of people dropping out of the trial due to adverse events (especially dizziness). The primary endpoint of SVC improvement wasn’t statistically significant and therefore the objective wasn’t met.

Cytokinetics are now testing a new drug, CK-2127107, that works on a similar principle as tirasemtiv. This drug is already showing to be better tolerated in an ongoing clinical trial (FORTITUDE-ALS) with healthy participants.


Already used to treat Parkinson’s disease, rasagiline was shown to have neuroprotective effects in pre-clinical trials. The results of their clinical trial with over 200 people did not show a significant difference in survival or measures of symptom progression between people taking rasagiline and those taking placebo.

Additional analyses looked at effects of rasagiline in subgroups of participants and found that, after 6 months on the treatment, there was a trend of slower disease progression in people with faster progression rate. While this effect disappeared with time, this trial highlights the importance of sample stratification – analysing results based on specific disease features, other than simply progression rate.


Ibudilast is a treatment developed by MediciNova for MND and Multiple Sclerosis, currently in Phase 2 clinical trial. Prof Benjamin Brooks reported that, based on the latest Phase 1B/2A clinical trial, Ibudilast was shown to be safe and well-tolerated when administered over 12 months.

Results of secondary outcome measures showed that, in some participants, the ALSFRS score didn’t decline. More detailed analyses revealed a connection between reduced disease progression while on ibudilast and higher survival rates after the treatment. These results however need to be confirmed in further, bigger trials that will determine the beneficial effects of ibudilast, as disease progression can be extremely variable.


Recent licensing of edaravone in USA sparked a lot of interest in this treatment. Dr Palumbo of Mitsubishi Tanabe Pharma summarised analyses of their latest clinical trial that showed slower symptom progression after 6 months of treatment as measured by ALSFRS. However, due to quite strict inclusion criteria (high functionality at the beginning of the study), this effect is likely to only be seen in a small subgroup of people with MND.

Looking at the data from the follow-up open label trial, in which everyone was offered edaravone, it appeared that those who were originally on placebo didn’t benefit from the treatment in the same way as people taking placebo from the beginning. This stressed the importance of early initiation of the treatment.

Dr Palumbo then talked us through possible improvements for future clinical trials, which included the reduction of heterogeneity of participants (that is, looking at effects of a treatment in those subgroups of people with the same or similar biological disease process).

We are not aware of any plans by Mitsubishi Tanabe Pharma to apply for marketing approval with the European Medicines Agency (EMA). This is likely due to the stricter criteria the EMA has for approval of new drugs, specifically with respect to short-term studies (as most clinical trials last 12-18 months) and lack of survival data.

Lithium carbonate

Presented in another session, and met with a lot of interest by the audience, was the recently published re-analysis of the lithium clinical trials. These showed that, unlike previously believed, treatment with lithium was in fact beneficial, but only in a subgroup of patients with a variation in the UNC13A gene. You can read more about this study in our previous blog.

You can find out more about Clinical trials and treatments on our Symposium LIVE webpages.


2 thoughts on “Lessons learnt in the past year…update on clinical trials

  1. Martina, I’d be interested to hear your views on the contributions from the pharmaceuticals industry to finding a cure. They have the budgets but are they engaged? How visible were they in Boston?

    • Dear Ken,

      Pharmaceutical companies are highly involved in the development of new treatments in so much as they fund their development, as you rightly mentioned. Pharma companies such as Cytokinetics, Biogen, Mitsubishi Tanabe Pharma and Biohaven Pharmaceuticals supported our Symposium and so this international meeting would be possible without their input. Other pharma companies, such as Italfarmaco, and Orion Pharma, were also present at the Symposium to talk about their work via presentations or ‘one-to-one’ sessions with any interested delegates.

      Best Wishes,


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