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http://mastcelldisorders.wallack.us/yabb/YaBB.pl General Mast Cell Disorders Discussion >> Medicines >> New MASTO Drug http://mastcelldisorders.wallack.us/yabb/YaBB.pl?num=1339377475 Message started by Joe on 06/10/12 at 14:17:55

Title: New MASTO Drug
Post by Joe on 06/10/12 at 14:17:55

During my last visit with Dr Castelles, she indicated that a new drug, PKC 412, was developed for Aggressive Systemic Mastocytosis and that it may be approved by the FDA and available for patients with ISM in about a year. She also said that their is currently a study going on to test the affects on ISM patients. I was curious if anyone on this forum is participating in this study and if so can you provide any information.

Thanks,
Joe

Title: Re: New MASTO Drug
Post by WendyH on 06/11/12 at 05:07:44

I believe Dr. Gotlib at Stanford is doing a study using this, its also called Midostaurin. Joan turned me on to him.

Title: Re: New MASTO Drug
Post by WendyH on 06/11/12 at 05:12:20

Joe I got Dr. Gotlib's email from the Stanford website and emailed him some questions (not about the drug) and he answered me the same day.
jason.gotlib@stanford.edu

Title: Re: New MASTO Drug
Post by mikev on 06/11/12 at 10:20:06

Joe:
Looking as a non-scientist at Midostaurin, I see that it's function looks to be the stoppage to growth in number of new cells, i.e mast cells or cancer cells, which is good for those who have an agressive version
of masto. For those of us who are diagnosed with SM w/ a kit mutation, it still appears to me that Masitinib, which my doc is now testing for his acute asthma patients, appears to be the better fit, as it's function is more to control the mast cells or pseudo mast cells that we already have. The interesting part of both drugs, is that we are getting a side benefit of drugs that main scope is cancer. Well as my doc said when we discussed Masitinib is there is no money in masto but lots of money in cancer & asthma.
mikev

Title: Re: New MASTO Drug
Post by Joan on 06/11/12 at 19:30:32

Midostaurin is being shown to be effective in patients with a C-Kit mutation. My understanding is that it kills mast cells, lowering the overall mast cell burden, not only in the bones, but also in the organs. Unfortunately, it kills them at a later stage when they've already reproduced, but is a tremendous step in the right direction. Since it targets only the mast cells, the side effects appear to be low, unlike other chemos which cause many other symptoms and can be really toxic to all blood cells, etc. The hope is that it can be used long-term. I believe it's in Phase II trials right now. Patients with ASM might qualify for a study and receive the drug free for life.

Studies are taking place at several locations.

Title: Re: New MASTO Drug
Post by mikev on 06/12/12 at 03:49:54

Joan:
Thanks for setting me straight. Will ask my doc what he knows on my next appt. I've been following Masitinib a long time & I know it's what DR V was testing @ MD Anderson as I was in touch with him about it.
It has finished phase 3 testing. The problem we all will have is getting our insurance companies to approve either of the drugs as I'm sure they both are going to be very expensive.
MikeV

Title: Re: New MASTO Drug
Post by Joan on 06/12/12 at 09:42:31

This is confusing for us lay-people, at best! I just read a published article citing the Phase 2 trial of Masitinib, and it said it was used for indolent systemic and cutaneous SM, NOT bearing the c-Kit mutation. I don't have time right now to check whether it's also been effective on those with the D816V Kit mutation, but I do know that Midostaurin is effective in people with that mutation.

Here's the link to the article I found describing the results of the Mastitinib human trial. At a glance, it appears to help with symptoms of SM and Cutaneous masto:

[url]http://www.4-traders.com/AB-SCIENCE-6133795/news/AB-SCIENCE-Publication-of-human-phase-2-results-of-Masitinib-in-the-treatment-of-mastocytosis-in-t-13484297//[url]

Here's one of Dr. Gotlib's older articles (2005) about Midostaurin, in case anyone wants to read about it:

[url]http://bloodjournal.hematologylibrary.org/content/106/8/2865.long/[url]

I'm sure there are some newer ones if you Google 'Midostaurin Human Trials' (or PKC412, its older name)

Mike, I believe Wash. U. has been a site for a Midostaurin Trial. The doctor who was the principle investigator may have left there, and I don't know the status of the study, but I would imagine your doc will know.

Title: Re: New MASTO Drug
Post by Joe on 06/14/12 at 06:25:42

Thank you for all the info, after checking my notes from my Drs visit I found that Dr. Castells was referring to PKC 412. I don't beleive this is the ame thing that you have been discussing here but not sure. Dr Castells did mention that it was being tested for use with ISM pts with D816V/C-kit mutation as well as AMS and was working well. Should be approved by next year according to the DR.

Title: Re: New MASTO Drug
Post by Joe on 06/14/12 at 06:29:59

Ok, I just read over the thread again and see that Midostaurin is the same as PKC 412. I 'll have to do some more research. Thanks everyone.

Joe

Title: Re: New MASTO Drug
Post by peter on 06/18/12 at 19:10:44

ha joe dont stop looking

Title: Re: New MASTO Drug
Post by peter on 06/23/12 at 18:40:34

http://www.scientistlive.com/European-Science-News/Pharmacology/Systemic_mastocytosis_treated/19757/

Patient with rare disorder responds to cancer drug
A rare disorder caused by an excess of two types of immune cells-the mast cell found in various tissues and its blood-based twin, the basophil-has successfully been treated with a cancer drug, report scientists from the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH). The study, now available on-line at the Web site of the journal Haematologica, was a collaborative effort led by Dean Metcalfe, M.D., chief of the NIAID Laboratory of Allergic Diseases and Jan Cools, Ph.D., a staff scientist, at the Katholieke Universiteit Leuven within the Vlaams Institute for Biotechnology and the Department of Molecular and Developmental Genetics, in Leuven, Belgium.

A few years ago, the 61-year-old patient was referred to the NIH Clinical Center because he was quite ill with symptoms of systemic mastocytosis, a disease caused by excessive numbers of mast cells, and chronic basophilic leukaemia, a rare type of bone marrow cancer characterised by an overabundance of basophils.

Systemic mastocytosis often results from a mutation in the gene that codes for the KIT receptor found on the surface of mast cells, a discovery first made by Dr. Metcalfe and his team in 1995. In this patient, however, the KIT receptor mutation was ruled out. In further studies, NIAID researchers and their collaborators found a chromosomal abnormality that led to the discovery of a fusion protein in the cell, created by two genes joining together. They also found that the fusion protein was the basis of the disorder and figured that the patient should respond to imatinib, a drug already approved to treat different types of cancers and systemic mastocytosis. After the patient was treated with the cancer drug imatinib, his clinical symptoms improved quickly and dramatically, and he remains in clinical remission three years after treatment was started.

This is a rare report of the simultaneous occurrence of these two conditions in one patient, and the first describing a response to therapy. Diagnosing a patient who has such an atypical disorder can be difficult, says Dr. Metcalfe. Recently, another patient with similar clinical findings was referred to their clinic. Based on their experience with the first patient, the researchers started treatment with imatinib and, according to Dr. Metcalfe, this patient also is responding well.

Identifying this newly recognised chromosomal abnormality and the fusion protein in patients who present with clinical findings of systemic mastocytosis and chronic basophilic leukaemia may enable doctors to successfully treat these individuals with imatinib, according to Dr. Metcalfe.

Title: Re: New MASTO Drug
Post by Baman on 07/12/12 at 00:02:47

Hi,
I am in the phase 3 Masitinib for Mastocytosis trial, and I DO have the D816V mutation. I think that the trial doctors are accepting anybody with biopsy confirmed mastocytosis who has several different handicaps and a reduced quality of life.
Often Masitinib does not affect tryptase levels much, though mine, 6 weeks into the trial, has never been lower.
On the other hand, Masitinib does have a huge effect on quality of life, but since most North American doctors are hypnotized by lab results, and never listen to their patients, this might go unnoticed.
In France, I have not had a single tryptase test. They say that tryptase is not indicative of disease severity.
And they really listen to me!!!
They gave all masto patients an MRI before the start of the trial, and another at the end. They believe in, and are trying to study the cognitive impairments associated with Mastocytosis.
Why are most North American doctors deaf?

Title: Re: New MASTO Drug
Post by mikev on 07/12/12 at 03:25:10

Baman:
Thanks for the update on masitinib. As I mentioned above, I've been watching it since Dr V was testing it at MD Anderson, but he's a cancer doc. My doc who is testing it in his chronic asthma patients explained it in a rather distinctive way, as to why he's was not interested in testing it with me & his other masto patients. He said there is no money in masto patients but lots of money in asthma or cancer patients. There is also a patient on the Canadian masto forum who is in France testing it & is having good luck as well. Another reason so much testing is in France is the drug is manufactured by a French company, AB Sciences. Thanks again for update & please keep them coming
MikeV

Title: Re: New MASTO Drug
Post by Spartako on 10/22/13 at 02:35:16

Any news on Midostaurin/PKC412 or Masitinib?

The Phase III Masitinib study may be delayed...
http://clinicaltrials.gov/ct2/show/NCT00814073?term=masitinib+mastocytosis&rank=1

Title: Re: New MASTO Drug
Post by Spartako on 01/07/14 at 16:14:11

http://finance.yahoo.com/news/ab-science-masitinib-successfully-passes-170251812.html

Quote:

The objective in this phase 3 study is to compare the safety and efficacy of masitinib to placebo in adult patients with Indolent Systemic Mastocytosis with severe handicap at baseline.

The futility analysis was included in the clinical study design to ensure that the study could be stopped early if it appeared that the study would be eventually unable to demonstrate the efficacy of masitinib in the target population of patients with Indolent Systemic Mastocytosis with severe handicap at baseline.

The analysis was performed with two-third of the target population to recruit. The futility analysis was performed by the independent Data and Safety Monitoring Board. It consisted in testing the possibility of masitinib to demonstrate superiority over placebo on the primary analysis set in the protocol, based on the EMA guideline on clinical trials in small populations (CHMP/EWP/83561/2005).

Alain Moussy, co-founder and CEO, stated "since the data remain blinded to AB Science, the efficacy results will not be known until the study is completed. However, we are very pleased that this pivotal clinical study has passed this important step successfully since the placebo effect was unknown as there has been no previous placebo controlled clinical study carried-out in this orphan disease".

http://finance.yahoo.com/news/ab-science-final-results-phase-174539052.html

Quote:

Final results of phase 3 mastocytosis study expected by end of 2014.
Indolent Systemic Mastocytosis is an orphan disease with no approved treatment so far.
Up to 20,000 treatable adult patients annually throughout countries paying for medication.
Long term follow up from phase 2 studies shows sustainability of response with masitinib.

Title: Re: New MASTO Drug
Post by Spartako on 08/14/14 at 19:44:06

There are some minor news on masitinib:
http://www.ab-science.com/file_bdd/1407256924_20140804clarificationconcernantlafabricationdumasitiniben.pdf

Quote:

The CHMP stated, upon completion of the assessment
of the application for conditional marketing
authorization of masitinib in second line treatment
of GIST and in pancreatic cancer, that “[...] there were concerns about the quality control of the medicineduring manufacture, which led to uncertainties aboutthe impurities that patients would be exposed to”.
This statement has been perceived as an indication
that there were problems in the manufacturing of
masitinib leading to the inadequate presence of imp
urities, and that such problems could be an obstacle
to the clinical development program or the registration of masitinib.
AB Science would like to reassert that the manufacturing
process of masitinib is robust and well under
control, meaning that batches produced consistently
meet the specifications, and in particular meet the
specifications set in recent guideline on acceptable
limit on mutagenic impurities.

http://www.ab-science.com/file_bdd/1407907527_20140813conclusionsurlacarcinogenicitedumasitiniben.pdf

Quote:

Observing the negative reaction from the market following
the clarification published on 10 August 2014,
AB Science (NYSE Euronext – FR0010557264 – AB) reasserts that:
-
The key message is that masitinib is not carcinogenic in humans.
-
Data collected to date from above 1600 patients who
received masitinib, some patients exposed
more than 7 years, show no sign of secondary malignancies.
-
Data in rodents were generated at the high dose from
80 to 160 times the dose administered to
humans and are not transposable to humans.
-
Those data from animal studies were communicated to
health authorities five years ago and were
validated by these authorities and do not represent
a new finding.
-
The clinical development program in non-oncology in
dications is on-going and will be carried-out
up to its term.

Still waiting on the finish of phase3 for mastocytosis...

Title: Re: New MASTO Drug
Post by mikev on 08/15/14 at 10:09:25

i have been watching progress of this drug for well over 2 years, in fact when dr v was testing it @ md anderson. my doc who's one of the top in country in asthma was involved in the phase 3 testing of it for severe asthma. he would not let me in his test group, as my asthma is not severe & i would taint results, i.e. didn't want to risk loosing his funding to help a long term patient of his who was basically begging him for help. this drug still looks a good option for those of us with ckit mut but the impurity problem busted it back atleast a couple years if not more. my doc did promise me he would go to the mat for me if it did every get approved, but ab science can't seem to solve the impurity issue up to fda's standards, so who knows when if ever this will be an option for us & if it was being tested again at phase 3 my doc would be involved & as of my last visit 4 months ago it wasn't.