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On Masitinib

I may have to revise my opinion of masitinib (which would not upset me in the slightest). Some of my readers may know that I have not been very optimistic about the probability of the drug being an effective treatment option for ALS. It’s been around for some time as a veterinary drug. But the company AB Science is developing it for ALS and other conditions.


Preclinical information appears encouraging, although the study has a few issues. The rat model is not like the mouse model and is not very suitable for a survival study. The survival data are also very difficult to interpret due to the curious use of different numbers of animals in each cohort. I will defer to the opinions of my more statistics-inclined members (please feel free to comment!). The cellular data have a similar issue because they were taken in vitro rather than vivo. Nevertheless, it’s encouraging and we can hope for quick human trials.

The press release.

The study (open access!).

And the first USA patient gets approval for Compassionate Use!

5 thoughts on “On Masitinib”

  1. Do be careful, a case of masitinib side effect in ALS patient has also been found:

    Autoimmune-like hepatitis during masitinib therapy in an amyotrophic lateral sclerosis patient

    Published online 2015 Sep 28.
    World J Gastroenterol


    We report a case of acute severe hepatitis resulting from masitinib in a young amyotrophic lateral sclerosis patient. Hepatotoxicity induced by masitinib, a tyrosine kinase inhibitor, is usually transient with mild elevation of transaminases, although acute hepatitis has been not reported to date. The hepatitis was resolved after masitinib was discontinued and a combination of prednisone and azathioprine was started. The transaminases returned to baseline normal values five months later. This is the first case in the hepatitis literature associated with masitinib. The autoimmune role of this drug-induced liver injury is discussed. Physicians should be aware of this potential complication.

    (Article text deleted by ENV)

    Source link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4579895/

    1. This is very useful, thanks for posting!

      As a general rule, it’s poor form to copy an entire article from one site to another. It violates copyright and good manners by using up a lot of space on the receiving site and denies the copied site the proper views. My readers can click and read the entire article as it is open access (yay proper sharing of knowledge!).

      Thanks again for adding great additional thought to the discussion. The cases seem rather rare but hepatitis is no fun, like eating bad mushrooms which return the favor by eating your liver.

    2. On 11 April 2017, the Agence Nationale de la Securite des Medicaments (ANSM) ordered a halt to all clinical trials in France of AB Science’s lead drug masitinib.

      The order resulted from an inspection by ANSM regulators that uncovered multiple violations by AB Sciences of the rules and procedures governing the conduct of masitinib clinical trials.

      ANSM said the reliability of efficacy and safety data from the AB Science clinical trials was in doubt. Patients enrolled in AB Science clinical trials were put at extra risk because toxicities related to masitinib were not fully disclosed.

      Please find the full ANMS statement here (in french): http://ansm.sante.fr/Decisions/Injonctions-decisions-de-police-sanitaire-interdictions-de-publicite-Decisions-de-police-sanitaire/Decision-du-11-05-2017-portant-suspension-des-essais-cliniques-promus-par-la-societe-AB-Science

    3. Following the EMA Inspection, on 18 May 2017, the EMA’s Committee for Medicinal Products for Human Use (CHMP) adopted a negative opinion, recommending the refusal of the marketing authorisationfor the medicinal product Masipro, intended for the treatment of systemic mastocytosis.

      The company that applied for authorisation is AB Science. It may request a re-examination of the opinion within 15 days of receipt of notification of this negative opinion.

      Masipro is a medicine that contains the active substance masitinib. It was to be available as tablets.

      Masipro was expected to be used to treat adults with systemic mastocytosis, a disease in which there are too many mast cells (a type of white blood cell) in the skin, bones and various body organs, causing symptoms such as itchy skin, hot flushes, palpitations, fainting, bone pain, weakness, vomiting, diarrhoea and depression.

      Masipro was designated an ‘orphan medicine’ (a medicine to be used in rare diseases) on 16 November 2004 for mastocytosis.

      The active substance in Masipro, masitinib, is a tyrosine kinase inhibitor. This means that it blocks enzymes known as tyrosine kinases, which can be found in some receptors in mast cells including those involved in stimulating the cells to grow and divide. By blocking these enzymes, Masipro helps to slow down the growth of the mast cells.

      What did the company present to support its application?

      The applicant presented data from a main study involving 135 patients with systemic mastocytosis who had severe symptoms including at least one of the following: itching, hot flushes, depression and weakness. In the study, Masipro was compared with placebo (a dummy treatment). The main measure of effectiveness was based on improvements in any of the four symptoms mentioned above after 24 weeks of treatment.

      What were the CHMP’s main concerns that led to the refusal?

      The CHMP was concerned about the reliability of the study results because a routine GCP (good clinical practice) inspection at the study sites revealed serious failings in the way the study had been conducted. In addition, major changes were made to the study design while the study was ongoing, which made the results difficult to interpret. Finally, data on the safety of the medicine were limited and there were concerns regarding the medicine’s side effects, including neutropenia (low levels of white blood cells) and harmful effects on the skin and liver, which were of relevance particularly because the medicine was to be used long term.

      Therefore, at that point in time, the CHMP was of the opinion that the benefits of Masipro did not outweigh its risks and recommended that it be refused marketing authorisation.

      Please find below, the link to the questions and answers on the refusal of marketing authorizations for Masipro (masitinib) below:

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