Masitinib trial in progressive MS

Epub: Vermersch et al. Masitinib treatment in patients with progressive multiple sclerosis: a randomized pilot study. BMC Neurol. 2012 Jun 12;12(1):36.

BACKGROUND: Treatment options for MSers suffering from progressive forms of MS remain inadequate. Mast cells actively participate in the pathogenesis of MS, in part because they release large amounts of various mediators that sustain the inflammatory network. Masitinib, a selective oral tyrosine kinase inhibitor, effectively inhibits the survival, migration and activity of mast cells. This exploratory study assessed the safety and clinical benefit of masitinib in the treatment of primary progressive MS (PPMS) or relapse-free secondary progressive MS (rfSPMS).

METHODS: Multicenter, randomized, placebo-controlled, proof-of-concept trial. Masitinib was administered orally at 3 to 6 mg/kg/day for at least 12 months, with dose adjustment permitted in event of insufficient response with no toxicity. The primary response endpoint was the change relative to baseline in the multiple sclerosis functional composite score (MSFC). Clinical response was defined as an increase in MSFC score relative to baseline of > 100%.

RESULTS: 35 MSers were randomized to receive masitinib (N = 27) or placebo (N = 8). Masitinib was relatively well tolerated with the most common adverse events being weakness, rash, nausea, swelling-oedema, and diarrhea. The overall frequency of adverse events was similar to the placebo group, however, a higher incidence of severe and serious events was associated with masitinib treatment. Masitinib appeared to have a positive effect on MS-related impairment for PPMSers and rfSPMSers , as evidenced by an improvement in MSFC scores relative to baseline, compared with a worsening MSFC score in MSers receiving placebo; +103% +/- 189 versus -60% +/- 190 at month-12, respectively. This positive albeit non-statistically significant response was observed as early as month-3 and sustained through to month-18, with similar trends seen in the PPMS and rfSPMS subpopulations. A total of 7/17 (41%) assessable masitinib MSers reported clinical response following 12 months of treatment (according to the modified intent-to-treat population, observed cases) compared with none in the placebo group. The Expanded Disability Status Scale remained stable for both treatment groups.

CONCLUSION: These data suggest that masitinib is of therapeutic benefit to PPMS and rfSPMS MSers and could therefore represent an innovative avenue of treatment for this disease. This exploratory trial provides evidence that may support a larger placebo-controlled investigation


“Masitinib is an interesting compound, from oncology, that targets an unusual suspect in MS, the mast cell. Mast cells are the cells that produce histamine, which makes us itch when we are bitten by insects for example mosquitoes. Mast cells may control permeability of blood vessels but it is not clear how this drug would act in progressive MS. It is likely to have off target effects. I hope the company takes this forward in progressive MS. Dare I suggest that the company uses changes in CSF neurofilament levels as an exploratory outcome measure to see that it works as a neuroprotective drug?”

9 thoughts on “Masitinib trial in progressive MS”

  1. How is MSFC different from EDSS?27 patients got the drug and they are saying 7/17 improved. Why is the denominator 17 and not 27?

  2. I get the impression that CSF neurofilament levels may be the true indicator to whether a drug to treat progressive MS is actually having a positive impact. The industry should use this method all the time as it will reduce trial times and provide scientifically robust data.

  3. I always wondered why an anti-Histamine was never tried (I have never found a study) in patients with MS.Histamin is one of the main information channels when it comes to inflammation. So it would be a good idea to block that channel. In my humble opinion…

  4. EDSS is a simple mobility scalehttp://en.wikipedia.org/wiki/Expanded_Disability_Status_ScaleIf you click on the MSFC you get a link to the MSFC, whichmeasures additional outcomes besides mobility.In any clinical trial you loose people to follow-up, such as they move away, they don't come back tosee you or they stop taking the drug because they feel it is not working or it has side-effects

  5. "I get the impression that CSF neurofilament levels may be the true indicator .."This one of our ideas we hope that the study using this will get off the ground

  6. Anti-Histamine for neuroinflammation in RRMS maybe be one approach but anti-histamine in PPMS/SPMS would probably be after a different target.

  7. Do other researchers accept the validity of using neurofilaments to shorten progressive MS trials?

  8. We will see when we get the reviewers comments back from out grant application..There are always ostriches around

  9. Re: "Do other researchers accept the validity of using neurofilaments to shorten progressive MS trials?"Yes, in particular the Swedes. In fact the Swedes are using CSF neurofilament levels as in routine clinical practice.

Leave a Reply to Gavin Giovannoni Cancel reply

%d bloggers like this: