Here is more news from the MSF Mailer I recently received. In addition to the news about Gilenya and CCSVI (See MS News Never Stops), the mailer discussed a number of other topics. Including, news that BG-12 appears to be showing positive results in its clinical trials:
Though detailed data has not yet been released, Biogen Idec has reported “top-line” results from the first phase three trial to evaluate the investigational oral compound BG-12 (dimethyl fumarate) as a monotherapy in people with relapsing-remitting multiple sclerosis (RRMS).
Results of the DEFINE trial showed that 240 mg of BG-12, administered either twice or three times a day, met the primary study endpoint, demonstrating a “highly statistically significant reduction” in the proportion of people with RRMS who relapsed at two years compared with placebo, Biogen said.
The company noted that both doses of BG-12 also provided a “statistically significant” reduction in annualized relapse rate, in the number of new or newly enlarging T2 hyperintense lesions, in new gadolinium-enhancing lesions, and in the rate of disability progression as measured by the Expanded Disability Severity Scale (EDSS) at two years.
Initial data from the trial showed that BG-12 demonstrated a favorable safety and tolerability profile, according to Biogen. The overall incidence of adverse events and serious adverse events was similar among the placebo group and both BG-12 treatment groups. The safety profile was consistent with what was seen in the published phase two study of BG-12. Further analyses of the DEFINE study are ongoing, and the company anticipates presenting detailed data at a future medical meeting.
Data from scientific studies suggest that BG-12 has the potential to be distinctive by reducing the entry into and the action of inflammatory cells on the central nervous system (CNS), as well as potentially protecting CNS cells from oxidative stress and death by activation of a critical pathway.
BG-12 received Fast Track designation from the U.S. Food and Drug Administration (FDA) in 2008. In addition to DEFINE, another phase three RRMS clinical trial, CONFIRM, is currently underway. This study is evaluating BG-12 and glatiramer acetate, against placebo. Clinical relapse, magnetic resonance imaging (MRI) measures of MS, progression of disability, and safety will be recorded. Results from CONFIRM are expected in the second half of 2011.
The mailer also, discussed the exciting progress laquinimod is making in its clinical trials:
The drug laquinimod reduced the number of relapses for people with MS in a large, long-term Phase III clinical study that was presented as late-breaking research at the 63rd Annual Meeting of the American Academy of Neurology, April 9–16, 2011, in Honolulu.Great to hear that such promising progress is being made on more oral therapies!
The study, supported by Teva Pharmaceticals, involved 1,106 people with relapsing-remitting MS in 24 countries. The participants received either a once-daily oral dose of 0.6 milligrams of laquinimod or a matching placebo for two years. Eighty percent of those taking laquinimod and 77 percent of those taking the placebo finished the two-year study.
Participants treated with laquinimod experienced a statistically significant reduction of 23 percent in annual relapse rate, compared to participants treated with a placebo. Additionally, there was a reduction of 36 percent in disability progression, as well as a 33 percent reduction in brain atrophy for those treated with laquinimod.
“These exciting results confirm that laquinimod has a significant impact on progression of disability and disease activity, while maintaining a high safety profile,” said lead author Giancarlo Comi, M.D., director of the Department of Neurology and Institute of Experimental Neurology at the Scientific Institute and University Vita-Salute San Raffaele in Milan, Italy.
“This may be attributed to the novel mechanism of action of laquinimod, which effectively and safely addressed both the acute inflammatory activity and the accumulation of irreversible tissue damage. This suggests a substantial future role for laquinimod in the treatment of MS.”
Laquinimod was safe and well tolerated, according to the study authors. Overall frequencies of adverse events were low and comparable to those observed in the placebo group. “The incidence of liver enzyme elevation was higher in laquinimod treated patients,” said Comi. “However, these elevations were temporary, reversible, and did not lead to any signs of liver problems.”
There was also information in the mailer regarding the research that may have discovered the driving force behind MS and may be on track to find a cure:
Neuroscientists have reported identifying a driving force behind autoimmune diseases such as MS, and suggest that blocking this cell-signaling molecule is the first step in developing new treatments to eradicate these diseases.For more about this topic, see Research Only Ends with a Cure. There were a few other topics discussed in the mailer, which I will discuss in the third and final series of the MSF Mailer news update.
Researchers led by Abdolmohamad Rostami, M.D., Ph.D., Professor and Chairman of the Department of Neurology at Jefferson Medical College of Thomas Jefferson University, found that GM-CSF, which stands for Granulocyte-macrophage colony-stimulating factor, appears to be the key culprit in the onset of MS. Without GM-CSF, T helper 17 cells (Th17) cells did not induce the MS-like disease in an experimental animal model.
These findings were recently published in an advanced, online publication of Nature Immunology.
Th17 cells have been shown to play an important pathogenic role in humans and experimental models of autoimmune diseases, but the mechanisms behind this have not been understood until now.
"There was no connection between GM-CSF and Th17 cells before," said Dr. Rostami. "What we have shown in this paper is that GM-CSF
"Now we know how the Th17 cells work and a better understanding of this mechanism and biology leads to new therapeutics," he adds.
The results suggest that blocking GM-CSF activity may be a successful therapeutic strategy in MS, one of the most common neurological diseases affecting young adults, and other autoimmune diseases, said Dr. Rostami, who is also the Chair of Neurology at Thomas Jefferson University Hospital.
These findings identify the interleukin-23 (IL-23)/ Th17/GM-CSF axis as the major pathway in pathogenesis of autoimmune central nervous system inflammation and likely other autoimmune diseases. IL-23, a known cytokine that causes autoimmune inflammation of the brain, induces production of more GM-CSF in Th17 cells, the researchers explain.
Dr. Rostami, who is also director of the Neuroimmunology Laboratory in the Department of Neurology at JMC, and his colleagues used an animal model of MS called experimental autoimmune encephalomyelitis (EAE) for the investigation, a common model used to study the pathogenesis of the disease. Mice whose Th17 cells cannot produce GM-CSF did not develop neuroinflammation, thus GM-CSF is responsible for disease manifestation in this experimental model.
Another recently published paper in Nature Immunology by Dr. Rostami and his team unraveled a mechanism that may help fight MS. The researchers found that a protein known as interkeukin-27 (IL-27) helped block, not induce, the onset of symptoms in animals with an MS-like disease. While increasing levels of GM-CSF may cause the disease, as shown in the current paper, increasing IL-27 concentrations may help quell an over-active immune system, the researchers reported.
In other news, I went to my first NMSS Advisory Board meeting and am going to continue to attend (making me an Advisory Board member)! I am so excited to be more involved in the fight against MS! Looking forward to helping out in any way that I can.
And a quick update on me: still feeling well - no everyday symptoms. I still experience some minor "flare-ups" when I get my core temperature up, but otherwise I am doing well! I am playing volleyball again tomorrow and I am going to try to play co-ed softball this summer (hopefully the heat doesn't get to me too much). I'll keep you updated!