Long Time, No Post

Sorry for the recent delay in posting.  I hope everyone had a Happy Thanksgiving!  My whole family got together which was great!  I have kept very busy lately, so I haven't had many chances to get on here to post.  Also, our computer got a virus, so we had to fix that before I could post.

And now, some news from the NMSS website:

The company Opexa Therapeutics (The Woodlands, TX) announced that the experimental therapy Tovaxin® has been designated by the U.S. Food and Drug Administration as a “Fast Track Product” for the treatment of secondary-progressive MS. Tovaxin is a personalized vaccine that aims to induce immunity against T cells that attack the brain and spinal cord in MS. It uses a person’s own immune cells, which are removed, manipulated, and then reintroduced by under the skin injections. The Fast Track designation may expedite its future review by the FDA after the company submits results of future phase III trials. The company is planning to begin a Phase IIb clinical trial of Tovaxin in secondary-progressive MS “subject to securing the necessary resources,” according to a November 8, 2011 press release.
Results so far: A one-year, multi-center trial of Tovaxin was conducted in 140 people with relapsing-remitting MS and 10 people who had experienced a neurological episode that put them at possible risk for being diagnosed with MS. The TERMS study found Tovaxin to be safe, but did not achieve statistical significance in the primary endpoint evaluating the cumulative number of active MRI lesions in those on active therapy versus those on placebo (Multiple Sclerosis, published online November 6). Analyzing a subset of participants after the study, investigators found that Tovaxin stabilized or reduced disability as measured by the EDSS scale, and the average number of relapses in a year.
Tovaxin is a trademark of Opexa Pharmaceutics.

This is VERY exciting because its focus is secondary-progressive MS rather than relapsing-remitting, which is what most therapies treat. Another article off of the NMSS website:

Genzyme has announced that the experimental intravenous therapy alemtuzumab (with a proposed brand name Lemtrada™) met two primary endpoints by significantly reducing relapse rates and the worsening of disability in a two-year study comparing alemtuzumab to standard subcutaneous dosing of Rebif® (interferon beta-1a, EMD Serono Inc. and Pfizer). The study, called CARE-MS II, involved 840 people with relapsing-remitting MS. The results were announced in a November 14, 2011 press release, which also indicated that the company plans to apply in early 2012 to the U.S. Food and Drug Administration for marketing approval. Data analysis is ongoing and the company expects to provide a full report at an upcoming medical meeting. Alemtuzumab has been designated by the FDA as a “Fast Track Product,” which should expedite its future review.
Background: MS involves immune system attacks against brain and spinal cord tissues. Alemtuzumab is a humanized monoclonal antibody directed at CD52 (a protein on the surface of immune cells) that is currently approved for the treatment of B-cell chronic lymphocytic leukemia. Its ability to target immune cells led investigators to test its potential as a treatment for relapsing-remitting MS. In an earlier phase II study comparing two dose levels of alemtuzumab with Rebif in 334 subjects with relapsing-remitting MS, those taking alemtuzumab had a 74% reduction in the risk of MS relapse compared with those on Rebif, and a 71% reduction in the risk for sustained worsening of disability (New England Journal of Medicine 2008 359;17:30-45).
Dosing was temporarily suspended in the Phase II study due to the occurrence of immune thrombocytopenic purpura (ITP), a rare condition in which low blood platelet counts can lead to abnormal bleeding. After the first cases of ITP occurred, one of which was fatal, Genzyme implemented a patient safety monitoring program which includes patient and physician education and regular contacts with patients.
Investigators recently reported on another phase III trial of alemtuzumab. The two-year CARE-MS-I phase III trial compared alemtuzumab against Rebif in 581 people with early relapsing-remitting MS. The study met one of two primary endpoints by reducing relapse rates by 55% over Rebif, but did not meet its second primary endpoint of slowing disease progression compared to Rebif. (Abstract #151, ECTRIMS 2011)
This Study: In the CARE-MS II study, 840 people with relapsing-remitting MS, who had experienced relapse while on a prior therapy, were randomly assigned to receive alemtuzumab or Rebif. Alemtuzumab was given by intravenous infusion for 5 days initially and for 3 days one year later. Those on Rebif received the standard dose of 3-times weekly subcutaneous injections. According to the company press release, after two years the relapse rate of those on alemtuzumab was reduced by 49% compared to those on Rebif, and the risk of sustained worsening of disability (as measured by the EDSS scale) was reduced by 42% compared to Rebif. (These were the primary endpoints of the study.)
According to the press release, approximately 16% of those treated with alemtuzumab developed autoimmune thyroid-related problems and approximately 1% developed ITP. All cases were detected early through a monitoring program and managed with conventional therapies. Other common adverse events associated with alemtuzumab included reactions associated with infusions (such as headache, rash, fever, flushing, hives and chills). The most common infections in those treated with alemtuzumab (all mild to moderate) were upper respiratory and urinary tract infections, sinusitis and herpes simplex infections.
Comment: The completion of this second Phase III trial of alemtuzumab is a milestone that paves the way for the company to apply to the FDA for marketing approval. Full details and evaluation of this study should help define the safety and promise of alemtuzumab as a potential new therapy for relapsing MS.

Love the ongoing research; I remain optimistic that a cure will come in my lifetime!  So many advances have been made in just the past decade alone!

Happy Veteran's Day + BG-12 Update

First, I want to thank the veterans for their service and dedication to our country, our safety, and our freedom!  

With that said, I attended an MS dinner/presentation last night about Stress and MS.  I cannot say that I really learned anything new, but it was a good reminder to keep stressors in check and to be sure to have a good coping system.  Life is stressful, MS adds extra stress, and we need to be able to have coping mechanisms in place to minimize the affects of stress.

Now for the BG-12 update (from the NMSS website):

Biogen Idec announced that the experimental oral therapy BG-12 significantly reduced the average number of annual MS relapses in a two-year, Phase III clinical trial of more than 1400 people with relapsing-remitting MS. Although its exact mode of action is not known, BG-12 is thought to inhibit immune cells and molecules involved in MS attacks on the brain and spinal cord. The results of the CONFIRM study were announced in an October 26 press release. Data analysis is ongoing and the company expects to provide a full report at an upcoming medical meeting. Positive results from another Phase 3 trial of BG-12 were also announced this year, paving the way for a potential application for marketing approval.

Background: Multiple sclerosis involves immune system attacks against brain and spinal cord tissues. Although its exact mechanism of action is not known, BG-12, an oral drug, is thought to inhibit immune cells and molecules and may be protective against damage to the brain and spinal cord. In an earlier phase II study, compared to inactive placebo, the highest tested BG-12 dose led to a 69% reduction in gadolinium-enhanced (a contrast agent) disease activity on MRI scans from weeks 12 to 24. Earlier in 2011, Biogen Idec announced positive results in another phase III study, the DEFINE trial. Further details on these results were presented at the joint meeting of the European and Americas Committee for Treatment and Research in MS (ECTRIMS/ACTRIMS) last week.

This Study: The primary goal of the CONFIRM study was to determine whether BG-12 could reduce the average annual MS relapse rate at two years. Secondary objectives included assessing BG-12’s effects on the proportion of people who had relapses, disability progression, and disease activity detected by MRI. Safety and tolerability were also assessed.
Participants were randomly assigned to one of two treatment groups receiving different oral doses (240 mg twice each day and 240 mg three times each day), a group receiving glatiramer acetate (Copaxone®, Teva Pharmaceutical Industries, an approved, injected therapy for MS) or a group receiving placebo. Both BG-12 groups and Copaxone were compared to the placebo groups, but not to each other.

According to the press release, in both groups taking BG-12, the primary endpoint was met; the average number of MS relapses in a year was reduced by 44% versus placebo in the lower-dose group, 51% in the higher-dose group, and 29% in the Copaxone group. Disease activity on MRI and the proportion of patients experiencing relapses also were reduced significantly more in the BG-12 groups versus placebo. Disability progression was not reduced significantly more in the BG-12 groups than in the placebo group. According to the press release, the most common adverse events in the BG-12 groups were flushing and gastrointestinal events.

Comment: Full details and evaluation of this study should help to define further the safety and promise of BG-12 as a potential therapy for relapsing MS. According to the company press release, these positive results set the stage for upcoming filings for marketing approval from drug regulatory agencies.

It is so exciting to learn that another oral therapy is doing well!  Hopefully soon, injections will be a thing of the past for all of us.  In the meantime, stick with what works.

New News from MSF

In this post: How cool would it be if MS could be diagnosed just by exhaling, BG-12 is showing progress, and odd hours may be a increase the risk of MS in teens, and should we be discussing walking problems with our doctors more?

The following is from my most recent email from the Multiple Sclerosis Foundation.

Diagnosing MS from Exhaled Breath

Scientists are reporting the development and successful tests in humans of a sensor array that can diagnose MS from exhaled breath, an advance that they describe as a landmark in the long search for a fast, inexpensive, and noninvasive test for MS. Their report appears in the journal ACS Chemical Neuroscience.

Hossam Haick and colleagues report have identified volatile organic compounds that can be associated with MS from exhaled breath. Based on these findings, the researchers developed a new sensor array that can diagnose MS by analyzing the determined chemical compounds that appear in the breath of people with MS. Using the developed sensors, the researchers carried out a proof-of-concept clinical study on 34 people with MS and 17 healthy volunteers and found that the developed sensors are just as accurate as a spinal tap but without the pain or the risk of side effects. 

"The results presented here open new frontiers in the development of fast, noninvasive, and inexpensive medical diagnosis tools for detection of chronic neurological diseases," the scientists stated. "The results could serve as a launching pad for the discrimination between different subphases of stages of multiple sclerosis as well as for the identification of multiple sclerosis patients who would respond well to immunotherapy." 

A large clinical study with the sensors is underway and will be reported in the future. Haick is a Professor in the Department of Chemical Engineering and the Russell Berrie Nanotechnology Institute at the Technion – Israel Institute of Technology. 

BG-12 Moves Forward with Positive Data from Late-Stage Trials
Positive top-line results have been reported from CONFIRM, the second of two pivotal phase III clinical trials designed to evaluate the investigational oral compound BG-12 (dimethyl fumarate) in people with relapsing-remitting multiple sclerosis (RRMS). Results showed that 240 mg of BG-12, administered twice a day (BID) or three times a day (TID), demonstrated significant efficacy and favorable safety and tolerability profiles. Further analyses of the CONFIRM study are ongoing, and Biogen Idec, the company developing BG-12, anticipates presenting detailed data at a future medical meeting.

BG-12 met the CONFIRM study's primary endpoint by significantly reducing annualized relapse rate (ARR) by 44 percent for BID and by 51 percent for TID versus placebo at two years. The CONFIRM study's reference comparator, glatiramer acetate (GA; 20 mg subcutaneous daily injection), reduced the ARR by 29 percent compared with placebo at two years. 

Initial results showed that BG-12 reduced 12-week confirmed disability progression as measured by the Expanded Disability Status Scale (EDSS) by 21 percent for BID and 24 percent for TID at two years compared to placebo, and GA reduced confirmed disability progression by 7 percent. 

"We now have strong positive results for BG-12 in two robust pivotal clinical trials with more than 2,600 patients," said Doug Williams, Ph.D., Biogen Idec's Executive Vice President of Research and Development. "We are gratified by these strong efficacy and safety results, which, when combined with BG-12's oral route of administration, position it as a potentially important MS therapy. We are working aggressively to prepare our regulatory submissions with the goal of making BG-12 available to MS patients as quickly as possible." 

In CONFIRM, both dose regimens of BG-12 showed favorable safety and tolerability profiles, which were similar to those seen in the previous late-stage study known as DEFINE. Overall, the incidence of adverse events (AEs), serious adverse events (SAEs) including serious infections, and discontinuations due to AEs were similar across all study groups, including placebo. The incidence of hepatic and renal events was also comparable among all study groups. The most common AEs in the BG-12 groups were flushing and GI events. There were no malignancies in the BG-12 groups. 

Biogen Idec presented data from DEFINE, at the 5th Joint Triennial Congress of the European and Americas Committees on Treatment and Research in Multiple Sclerosis (ECTRIMS and ACTRIMS) in October 2011.

 

Working Overnight or Odd Shifts May Increase MS Risk in Teens

Working overnight or odd shifts may increase teenagers' risk of developing MS, according to the results of an observational study. 

Researchers from Sweden who uncovered the link said interruption of circadian rhythms and disruption of normal sleep patterns may be partially responsible for the added risk.

In conducting the study, published in the Oct. 18th issue of Annals of Neurology, researchers examined two population-based studies of Swedish residents aged 16 to 70 (one with incident cases and one with prevalent cases) to compare the number of cases of MS among those who did and did not work overnight or shift hours on a regular or alternating basis during their teens.

Among the incident cases, the investigators found those who worked overnight hours for three years or more before the age of 20 were twice as likely to develop multiple sclerosis as those who never worked night shifts. Among the prevalent cases, they noted, the teens who worked overnight hours were slightly more than twice as likely to develop the disorder.

"Our analysis revealed a significant association between working shift at a young age and occurrence of MS," Dr. Anna Karin Hedstrom, of the Karolinska Institute in Stockholm, said in a journal news release. "Given the association was observed in two independent studies strongly supports a true relationship between shift work and disease risk." 

The researchers explained the sleep restriction associated with working the night shift has already been shown to increase the risk for certain health problems, including heart disease, thyroid disorders and cancer, likely by interfering with melatonin secretion and increasing inflammatory responses. 

The authors pointed out that since MS is a central nervous system autoimmune inflammatory disorder that is linked to a person's environment, other lifestyle risk factors, such as sleep loss due to shift work, should also be considered.

The study authors noted that more research is needed to explain why the disruption of circadian rhythm and sleep loss increase teenagers' risk for developing MS.

 

MS Walking Problems Rarely Discussed

Most people with MS who have difficulty walking say it is the most challenging part of the debilitating disease, U.S. researchers say. However, a survey by Harris Interactive indicated 40 percent of people with MS rarely or never discuss walking problems with their doctor. 

The recent survey of more than 1,200 adults living with MS indicated 65 percent reported having trouble walking, the inability to walk, or difficulty maintaining balance at least twice per week. Seventy percent of those with walking issues say that's the toughest symptom to deal with.

In addition, a majority of people living with MS reported they experienced walking problems within the first few years after diagnosis, while among people diagnosed with MS within the past five years, 58 percent reported experiencing a mobility issue at least twice a week.

On average, people with MS ages 41 or younger who do discuss trouble walking with their doctor initiate the conversation only 46 percent of the time. An estimated 78 percent of these women and 62 percent of these men report that trouble walking makes getting around dangerous, the survey indicated.

In light of the increasing menu of therapeutic options, assistive technology, and medication to aid walking problems, conversations with your doctor may lead to solutions.

 

As always, the ongoing studies and research is much appreciated!  Being able to diagnose MS with just a breath is incredible!  Disruption of normal sleep habits increasing the risk of MS makes me reevaluate my sleeping habits and makes me think back to my teenage sleep patterns (probably not the best, but what teenager truly has good sleeping habits?).  I am always happy to hear that clinical trials are going well for up and coming therapies!  Go BG-12!  

Thanks for reading!  Hope everyone is well!