Saturday, March 30, 2013

FDA announces approval of dimethyl fumarate

Dimethyl Fumarate
On March 27, 2013 Dimethyl fumarate has won FDA approval to treat relapsing-remitting forms of multiple sclerosis and will be sold under the name Tecfidera also known as BG-12, manufactured by Biogen Idec.
The drug has been used for many years in Europe to treat psoriasis, and since the 1980’s as a fungicide.
Dimethyl fumarate is unlike all previous MS “disease-modifying drugs” (DMDs) which all work by eliminating T lymphocytes and/or preventing them from crossing the blood-brain barrier.  It thus represents a “radical change in multiple sclerosis pathogenesis” according to van Horssen a long-time leading MS researcher.  Instead, dimethyl fumarate is an “anti-oxidant” which means that it reduces “reactive oxygen species” which in turn reduces free radicals. For years health specialists have been extolling the importance of anti-oxidants such as green tea and turmeric to delay ageing.  But recent research has demonstrated that the oligodendrocytes that make myelin are extremely sensitive to free radicals. Dr. van Horssen reported at ECTRIMS in 2011 that dimethyl fumarate exerts its protective effect via activation of the nuclear-factor-E2 (Nrf2) transcriptional pathway that is involved in the production of antioxidant enzymes necessary for oxidative stress defense.  He stated that distinct Nrf2 activators like dimethyl fumarate boost antioxidant enzyme production in oligodendrocytes and limit ROS-mediated oligodendrocyte death.
Two placebo-controlled phase III trials served as the basis for the FDA approval.  A total of about 2,700 patients were studied. In addition to comparing the drug with placebo, dimethyl fumarate was also compared to glatiramer acetate (Copaxone).
At the 2013 annual meeting of the American Academy of Neurology Robert Fox, MD reported that MRI T2 lesions were reduced by 72% at 6 months and 82% at two years.  Gadolinium-enhancing lesions were reduced by 83% at 6 months and 83% at two years.  This is much better than the immunosuppressants drugs.  It was also superior to Copaxone.
The main side effect was gastrointestinal complaints.  There has also been a case report of one 72 year-old man who developed PML on Fumaderm the name of the drug in Germany that has recently been purchased by Biogen.
Biogen obtained a use patent for dimethyl fumarate in 2009.  It is important to note this was a “use” patent; Biogen did not invent dimethyl fumarate that has been available for decades.  They patented the preparation of it in enteric-coated micro-tablets to reduce the GI irritation in a dose designed to deliver approximately 100 mg of fumaric acid to treat multiple sclerosis and other conditions.

Dr. van Horssen also compared Biogen’s formulation called BG-12 to Protandim, an over-the-counter Nfr2 activator dietary supplement in an in vitro (human oligodendrocyte cells in a petri dish, not in vivo, skeptical and gullible human beings).   He found that Protandim was actually superior to BG-12, as the “most potent induction of Nfr2-driven antioxidant enzyme production in oligodendrocytes” (ECTRIMs 2011).

Biogen recommends taking the 120mg capsule twice daily, increasing to two (2) twice daily after a few weeks.  Based on their 2009 patent this would be approximately 100mg of fumeric acid, but we are still looking into this conversion question.  Although Biogen has not announced how much they will charge for their new drug, it is likely that it will be about the same as the other DMDs, i.e. about $40,000 per year.  Protandim is expensive but costs about $40 per month or $480 per year, but currently will not be reimbursed by insurance companies.  It contains several herbs that are high in fumeric acid including green tea extract and turmeric extract.  The company that makes Protandim typically recommends one tablet a day.  David Perlmutter MD (author of “”) recommends that patients with neurodegenerative disorders such as MS take one twice daily of  another brand of Nfr2 Activator made by Xymogen which also contains green tea and turmeric extracts.  One can take the herbs themselves but it will be important to make sure that an adequate quantity is taken and there may be more GI irritation at higher doses. Terry Wahls MD (author of “Minding My Mitochondria”) recommends 3 cups per day of intensely colors vegetables and fruits such as beets, carrots, squash, berries and peaches. Non-denatured whey is also a source of anti-oxidant stimulation.  Ann Boroch CNC (author of “Healing Multiple Sclerosis”) also recommends anti-oxidants ideally from foods but also several supplements including  Antioxidant Supreme made by Gaia Herbs.  We are continuing to look into the appropriate conversion between Tecfidera and other formulations.  Since Biogen has spent many millions to prove dimethyl fumarate’s efficacy, it will be worthwhile to try to obtain adequate quantities of similar Nrf2 activators from other formulations.

Summary:  A multi-million dollar FDA trial has proven that taking Nfr2 activators dramatically reduces MS.  The mechanism of action is the reduction of oxidative stress, not immunosuppression.  This mechanism is in keeping with the inflammation/brain vein drainage model (in contrast to the orthodox autoimmune attack on intact myelin by T cells model).  We believe that everyone should be taking it, whether prescribed by neurologists – Tecfidera, or by naturopaths – Protandim, Xymogen, diet, or herbal supplements. 

Monday, March 4, 2013

FDA Update

Here's a brief summary of where we stand with the FDA to date: 
May10,2012 FDA stops all CCSVI research
May17,2012  Hubbard Foundation requests an exemption from the FDA
Sept 15,2012 FDA responds with a list of recommendations
Jan 7,2013 Hubbard Foundation submits a formal IDE application
Feb 8,2013 FDA responds with additional recommendations.
 It does appear the FDA will approve our Registry to continue studying CCSVI in MS.

For those of you who are interested in having the procedure please see our map of IR sites who are ready to begin once we get FDA approval.

Let's go with the flow!