Blue Ridge Chapter Weekly E-list Update
October 29, 2008
Contents:
Programs:
1. Stress Management Workshop
2. Couples workshop in Lynchburg
Other News:
3. JAUNT and CTS free on election day in Charlottesville
4. Alemtuzumab Results Published: Reduced MS Relapses and Accumulation of Disability in Phase 2 Trial -- Phase 3 Trials Recruiting Patients
5. Results Published: Oral Drug BG00012 Reduced MRI Inflammation in Relapsing-Remitting MS During Phase 2 Trial -- Phase 3 Trials Recruiting Patients
Programs:
1. Stress Management Workshop
As the holidays approach and schedules get busier and busier, stress can build. How can you cope successfully? Attend a stress management program and learn more about strategically managing stress in your life.
Our presenter for this program is Dr. Robert Smith, a clinical psychologist. He has specifically tailored this stress management program to people with multiple sclerosis. Dr. Smith will address ways to cope effectively with the added stress of MS in your life.
Program Date:
November 4, 2008
-
Christiansburg: 7pm at the Health and
Make this holiday season less stressful. Learn tips and tools to improve your life. Take part in one of these free, informative sessions near you!
Register by calling
1-800 344-4867 or (434) 971-8010.
2. Couples workshop in Lynchburg
Save the Date...for a very special opportunity in
For more details, click here.
Other News:
3. JAUNT and CTS free on election day in Charlottesville
Charlottesville Transit Service (CTS) and JAUNT will offer free transportation in Charlottesville
4. Alemtuzumab Results Published: Reduced MS Relapses and Accumulation of Disability in Phase 2 Trial -- Phase 3 Trials Recruiting Patients
Treatment with alemtuzumab (Genzyme Corporation) reduced the accumulation of disability and the frequency of relapses in people with early relapsing-remitting MS, compared to Rebif (interferon beta-1a, EMD Serono, Inc. and Pfizer, Inc.). 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 accumulation of disability. Those on alemtuzumab, an immune-suppressing monoclonal antibody, experienced adverse events more frequently, including immune thrombocytopenic purpura (a serious bleeding disorder), thyroid adverse events, and infections. The results, originally reported at medical meetings, have now been published (New England Journal of Medicine 2008 359;17: 30-45), and two Phase 3 trials are currently recruiting participants with relapsing-remitting MS.
Background and Details
Alemtuzumab is a humanized monoclonal antibody directed at CD52 (a protein on the surface of immune cells) that is currently approved by the U.S. Food and Drug Administration as a single agent for treatment of patients with B-cell chronic lymphocytic leukemia. Its ability to target immune cells has led investigators to test its potential as a treatment for relapsing-remitting MS.
Drs. D. Alastair Compston, Alasdair J. Coles (University of Cambridge, UK) and colleagues have now published results of phase 2 clinical trial that compared high and low doses of alemtuzumab (given by IV infusion over three to five days once a year) with Rebif, a standard MS therapy, in 334 people with early relapsing-remitting MS who had never taken any other disease-modifying therapies. The primary outcomes were the time to sustained accumulation of disability and the rate of relapse.
Those in the alemtuzumab groups were slated to receive two to three cycles of the annual infusion. However, dosing was temporarily suspended 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. A total of six alemtuzumab-associated ITP cases were identified and, when necessary, promptly treated.
Most of those on alemtuzumab received their second infusion cycle (207 out of 223 total), but fewer went on to receive a third cycle (46 out of 223). The results reported in this publication follow the participants out to 36 months of the study.
Results
The results were nearly the same for the two doses of alemtuzumab, so the data for patients receiving this drug were pooled for the comparison with Rebif. After thirty-six months, those taking alemtuzumab experienced significant reductions in the risk of MS relapse compared with those taking Rebif (74% reduction, with an annualized relapse rate of 0.36 for Rebif versus 0.10 for alemtuzumab) as well as significant reductions in the risk for progression of disability compared with those taking Rebif (71% reduction). Among secondary outcomes that were measured, significantly more of those on alemtuzumab remained relapse-free at 36 months (52% for Rebif and 80% for alemtuzumab). In addition, the mean disability score (EDSS) for those on alemtuzumab improved slightly (by 0.39 point) while the mean score of those on Rebif declined slightly (by 0.38 point).
Among other side effects reported in the Phase 2 study, patients who received alemtuzumab were more likely to develop thyroid disease and mild to moderate infections (i.e., infections requiring no specific medical intervention or requiring only oral medication). Thyroid problems are reported to have been easily detected and treated. Patients who received Rebif experienced injection site reactions, fatigue, flu-like illness, headache and abnormal liver function tests.
Comment
“We are pleased to see potential new treatment options move positively through the MS pipeline,” said John R. Richert, MD, executive vice president for research and clinical programs at the National MS Society. “We look forward to results from the Phase 3 studies now getting underway, which will help determine if this treatment can be used safely and effectively in people with MS.”
Two Phase 3 trials of alemtuzumab, supported by Genzyme Corporation and Bayer Healthcare Pharmaceuticals, are currently recruiting participants: http://www.nationalmssociety.org/research/research-news/news-detail/index.aspx?nid=231
-- Research and Clinical Programs Department
Rebif is a registered trademark of EMD Serono, Inc. and Pfizer, Inc.
5. Results Published: Oral Drug BG00012 Reduced MRI Inflammation in Relapsing-Remitting MS During Phase 2 Trial -- Phase 3 Trials Recruiting Patients
Results of a multicenter, controlled clinical trial of oral BG00012 (dimethyl fumarate, Biogen Idec, Inc) involving 257 people with relapsing-remitting MS have now been published, showing that, compared to inactive placebo, the highest tested dose led to a 69% reduction in active inflammation on MRI scans from weeks 12 to 24. Adverse events included abdominal pain, flushing, headache, fatigue, and feeling hot. The study was conducted by Dr. Ludwig Kappos and colleagues, and results are published in the October 25, 2008 issue of The Lancet (2008 372:1463-1472). Based on these positive results, the sponsor is recruiting people with relapsing-remitting MS for two large-scale, Phase 3 clinical trials.
Background and Study Design
Multiple sclerosis occurs when the immune system mistakenly attacks nerve fiber-insulating myelin and other brain and spinal cord tissues. Although its exact mechanism of action is not known, BG00012, an oral fumarate, is thought to inhibit immune cells and molecules and may be protective against damage to the central nervous system.
For this Phase 2 study, 257 people with relapsing-remitting MS were assigned to receive a low dose, medium dose or high dose of daily oral BG0012, or inactive placebo, for 24 weeks. Participants were aged 18-55, with no to moderate disability (EDSS scores ranging from 0 to 5), and had had at least one relapse within one year of the study or MRI scans showing active disease.
The study was designed with a primary outcome to be a comparison of the total number of new, active brain lesions (as seen on MRI scans using gadolinium, an enhancing agent) at four-week intervals starting with week 12. The investigators also collected data on other MRI findings, relapse rates, and safety.
Results
Compared with those on placebo, the treatment group on the highest dose of BG00012 had a 69% reduction in the mean total number of new enhancing MRI lesions from weeks 12 to 24. The drug also reduced the number of other types of new or enlarging MRI lesions. No significant difference was seen in relapse rates, but the study was not designed to adequately detect clinical differences.
Based on the anti-inflammatory effects seen on MRI, the sponsor is proceeding with two large-scale, Phase 3 clinical trials of BG00012 in relapsing-remitting MS. Participants are being sought for the two trials, known as the DEFINE study and the CONFIRM study.
Learn more about the possibility of participating in one of these clinical trials:
http://www.nationalmssociety.org/research/research-news/news-detail/index.aspx?nid=70
Comment
“We are encouraged by the MRI data from this publication,” says Patricia O’Looney, PhD, Vice President of Biomedical Research for the National MS Society. “We look forward to seeing further clinical and safety data from the phase 3 studies, which will help to determine if this oral therapy can be used safely and effectively in people with MS.”
-- Research & Clinical Programs Department
Background and Details
Alemtuzumab is a humanized monoclonal antibody directed at CD52 (a protein on the surface of immune cells) that is currently approved by the U.S. Food and Drug Administration as a single agent for treatment of patients with B-cell chronic lymphocytic leukemia. Its ability to target immune cells has led investigators to test its potential as a treatment for relapsing-remitting MS.
Drs. D. Alastair Compston, Alasdair J. Coles (University of Cambridge, UK) and colleagues have now published results of phase 2 clinical trial that compared high and low doses of alemtuzumab (given by IV infusion over three to five days once a year) with Rebif, a standard MS therapy, in 334 people with early relapsing-remitting MS who had never taken any other disease-modifying therapies. The primary outcomes were the time to sustained accumulation of disability and the rate of relapse.
Results of a multicenter, controlled clinical trial of oral BG00012 (dimethyl fumarate, Biogen Idec, Inc) involving 257 people with relapsing-remitting MS have now been published, showing that, compared to inactive placebo, the highest tested dose led to a 69% reduction in active inflammation on MRI scans from weeks 12 to 24. Adverse events included abdominal pain, flushing, headache, fatigue, and feeling hot. The study was conducted by Dr. Ludwig Kappos and colleagues, and results are published in the October 25, 2008 issue of The Lancet (2008 372:1463-1472). Based on these positive results, the sponsor is recruiting people with relapsing-remitting MS for two large-scale, Phase 3 clinical trials.
Background and Study Design
Multiple sclerosis occurs when the immune system mistakenly attacks nerve fiber-insulating myelin and other brain and spinal cord tissues. Although its exact mechanism of action is not known, BG00012, an oral fumarate, is thought to inhibit immune cells and molecules and may be protective against damage to the central nervous system.
For this Phase 2 study, 257 people with relapsing-remitting MS were assigned to receive a low dose, medium dose or high dose of daily oral BG0012, or inactive placebo, for 24 weeks. Participants were aged 18-55, with no to moderate disability (EDSS scores ranging from 0 to 5), and had had at least one relapse within one year of the study or MRI scans showing active disease.
The study was designed with a primary outcome to be a comparison of the total number of new, active brain lesions (as seen on MRI scans using gadolinium, an enhancing agent) at four-week intervals starting with week 12. The investigators also collected data on other MRI findings, relapse rates, and safety.
Click here to view the very latest research news on the National MS Society website.
The Blue Ridge Chapter of the National Multiple Sclerosis Society is proud to be a source of information about multiple sclerosis. Our comments are based on professional advice, published information, and expert opinion, but do not represent therapeutic recommendation or prescription. For specific information and advice, consult your qualified physician.
The Blue Ridge Chapter of the National Multiple Sclerosis Society does not endorse products, services, or manufacturers. Such names appear here solely because they are considered valuable information. The chapter assumes no liability whatsoever for the contents or use of any product or service mentioned.