I keep track of what’s on the horizon as far as MS research is concerned. Given it takes many years for products to come to fruition with all the studies that need to be done in order to be considered for FDA approval, something that looks good in the beginning can fall flat somewhere along the route. BG-12, now known as Tecfidera, had my interest in its infancy as a drug.
I was so impressed with the data that it was the one drug I had even considered a substitute therapy—to finally leave Betaseron and the injections behind seemed a real possibility.
On March 15, 2013, my neurologist emailed to alert me of BG-12’s release date: 3-27-13. Two days before her email arrived I was in the ER with an allergic reaction to Carbamazepine (unknown at the time), and I already had the rash and severe itchiness to prove I had a problem with some unknown agent. The allergic reactions and skin problems continued in Japan as mentioned previously. By the time I returned home, although I was no longer taking Carbamazepine, I had changed the nature of my skin. I seemed to be literally keratinizing my shoulders, arms, chest, scalp, and upper back with my constant scratching.
When I saw my neurologist in April, she admitted that nobody knew how long these side effects would continue even though I had stopped the drug that had caused this to take place. I knew that I couldn’t begin BG-12 as:
• The most common side effects of Tecfidera in clinical studies were flushing (redness, itching, or rash) and stomach problems.
My neurologist signed me up with Biogen to enroll for BG-12, but I was seriously depressed. Finally, the drug that I had waited for had been approved, but I couldn’t take it due to the ongoing complications from another pharmaceutical.
To pass the time, I begin to delve further into the research behind BG-12. Once a drug is approved by the FDA, it is quite typical for a lot of previously unknown information to be divulged or uncovered by the scientific community, the drug company, and the inquisitive public.
I was aware that people had been looking into the fumaric acid esters for psoriasis treatment since 1959. A specific mixture of dimethyl fumarate and monoethyl fumarate salts was licensed in Germany as an oral therapy for another auto-immune disease,
psoriasis, under the trade name Fumaderm in 1994.
The patent for use of dimethyl fumarate with MS by Fumapharm AG has a filing date of 2002 (pub date 2008). Biogen Idec acquired Fumapharm AG in 2006 and with it the rights to its psoriasis drug Fumaderm. Since 1996 Biogen had an interferon on the market for the treatment of MS, Interferon b-1a (Avonex), it makes sense that finding a novel way to impact the immune system might be advantageous for many auto-immune disorders so once Fumaderm had been successfully used with psoriasis, why not look at MS?
There was a ban on dimethyl fumarate in the EU in 2009 as:
• The use of the biocide (DMF) dimethyl fumarate – which has caused severe allergic reactions in hundreds of consumers, because of its use in every day consumer products such as couches and shoes
Seems that furniture manufactured in China and imported to the EU had packets sewn into it which resulted in the allergic reactions of the new owners and eventual ban in the EU.
This bit of information was bothersome given I was already having severe allergy problems. If others were having difficulty just sitting on a sofa that had been treated with dimethyl fumurate, I was concerned about what it might do if you ingest a similar compound until I read the following:
• BG-12 started in one indication and switched when MS patients with psoriasis reported dramatic improvements their MS symptoms. By April 2011, Biogen was reporting impressive top-line results from the DEFINE and CONFIRM Phase 3 trials in more than 2,500 patients with relapsing-remitting multiple sclerosis.
In 2011 a short article was published (funding from Biogen Idec ) with the following aim:
• Objectives: To investigate the potential of different Nrf2 activators to boost antioxidant enzyme expression in oligodendrocytes and protect them from reactive oxygen species (ROS)-mediated cell death.
BG-12 and several other compounds were tested including Protandim with the following results:
• Interestingly, protandim, a dietary supplement consisting of herbal ingredients, was the most potent inducer and therefore may be the most suited as a therapeutic strategy.
Protandim already belonged to LifeVantage; Biogen did the smart thing and went forward with BG-12 as a therapy for MS.
BG-12 works through the Nrf2 pathway which is involved with how your body protects itself against oxidative stress, inflammation, and, thereby, neurodegeneration. This is a very different approach than that of the drugs that had been previously released interferons which are believed to reduce the overall immune response directed against the CNS. As with any approach, however, there are caveats to using the Nrf2 pathway—basically that cancer cells may be able to manipulate the system and generate their own antioxidants to promote their survival.
A small, but necessary, detour as we recall Biogen’s MS drug Tysabri (Natalizumab) which was approved in 2004 but withdrawn in 2005 after being linked to three cases of progressive multifocal leukoencephalopathy (PML). It was ultimately put on the market in 2006 after a review of its safety data, the addition of black box warnings plus a special prescription program, and the intense lobbying by MS patients.
Biogen then came out with a test for the JC Virus to help people determine their risk of developing PML.
It, obviously, caused a certain amount of concern in the MS population awaiting BG-12 when several PML cases were seen with Fumaderm use for psoriasis:
• Background: Fumaric acid and/or its derivates were found to be effective and safe in the treatment of psoriasis vulgaris. In addition, treatment with fumaric acid is currently evaluated in phase II/III trials for the therapy of multiple sclerosis. PML is a rare but frequently fatal disease caused by the uncontrolled replication of JC virus (JCV), a polyomavirus, in the brains of some immunocompromised individuals, including 4 to 5% of HIV-positive patients with AIDS, also occurring in association with leukemia and lymphoma.
• In response to the queries regarding BG12, fumarates and PML. Yes, there have been 4 cases of PML in people on Fumaderm for psoriasis. One of these cases has been presented at an academic meeting in Germany and the abstract is presented below all the cases that have been reported via the German Adverse Drug Reaction Database (below).
Please remember, however, that Fumaderm and BG-12 are not the same drug:
• Fumaderm and Tecfidera are “chemical cousins,” not identical copies, said Eric Schmidt analyst at Cowen & Co. in New York. Many psoriasis patients in Germany get the Tecfidera “look-a-like” drug, he said.
The drones from Biogen still call me occasionally to ask when I’m going to start Tecfidera. I tell them that I don’t plan to do so. This is clearly NOT in their script. Where does this leave me? Happy that I don’t have to deal with the decisions about taking BG-12 and possibly risking PML. Also I’m VERY happy that I am taking the approach of functional medicine rather than altering my body’s normal biology. Given my propensity towards allergic reactions, rashes and the like, in the end I have a feeling that I wouldn’t have been a good candidate for BG-12 anyway.
Rheumatoid Arthritis symptoms are absent, and Multiple Sclerosis continues to steadily improve on my functional medicine protocol without the use of pharmaceuticals.
I never thought I’d look fondly on trigeminal neuralgia or Carbamazepine, but I would like to think that things happen for a reason.
extra credit for geeks:
Nrf2/INrf2 (Keap1)”>Signaling in Oxidative Stress and Cellular Protection