Research News
Tysabri® Update
Good news for patients previously on Tysabri no new cases of PML
Biogen Idec and Elan Corporation, makers of Tysabri® (natalizumab), have conducted a safety evaluation of patients who previously took Tysabri. Any unusual responses to the drug are being investigated and reported to the FDA. Three cases of progressive multifocal leukoencephalopathy (PML) have resulted in two deaths so far in patients on Tysabri. PML is an often-fatal brain disorder thought to be caused by the activation of a virus known as the "JC Virus."
According to a press release from Biogen Idec and Elan, dated August 9, 2005, no new confirmed cases of PML have been discovered. Almost 2,000 MS patients from clinical trials participated in the safety evaluation. With no additional cases of PML among patients exposed to Tysabri, Biogen Idec and Elan are taking preliminary steps to restart clinical trials in MS.
For more information, please see "Recent News" on MSAA's website at www.msaa.com, or call MSAA at (800) 532-7667.
Interim Results from Campath® Trial
Encouraging results although some adverse events
In September 2005, Genzyme Corporation and Schering AG Germany announced the interim results of a phase II trial comparing Campath® (alemtuzumab) with Rebif® (interferon beta-1a). These results came from an efficacy (looking at effectiveness) and safety interim analysis, following the completion of one year of treatment in a planned three-year trial with active relapsing-remitting MS patients.
Campath is a humanized monoclonal antibody that binds to a specific target (CD52) on cell surfaces, directing the body to destroy potentially damaging cells within the immune system. For these studies, Campath is administered in annual intravenous (directly into the vein) infusion regimens (a five-day course of doses is given the first year; a three-day course of doses is given during the second year and beyond).
According to the companies' announcement, the one-year interim analysis showed a 75 percent reduction in relapse rate and a 60 percent reduction in the risk for progression of clinically significant disability for individuals treated with Campath, as compared to those receiving Rebif. Serious adverse events, however, occurred in two participants on Rebif, four participants on the low dose of Campath, and five participants on the high dose of Campath.
Three documented cases of idiopathic thrombocytopenic purpura (ITP) occurred in the Campath groups (causing a low platelet count with the potential for abnormal bleeding). One of these three cases resulted in death; the other two individuals affected are responding to treatment. Two participants taking Campath developed Graves' Disease (a treatable thyroid condition). The companies are not disclosing details about the adverse events which were experienced by six other study participants, except to say that none of the adverse events were unexpected and that no cases of progressive multifocal leukoencephalopathy (PML) have occurred.
The companies are implementing safety provisions and have consulted with the United States Food and Drug Administration (FDA). The companies have temporarily suspended the dosing of Campath in this study.
MSAA Vice President and Chief Medical Officer Dr. Jack Burks explains, "Campath is not FDA approved at this time for the treatment of MS. While these early results are encouraging, patients needing treatment today should not delay being treated with currently available therapies, if advised by their treating MS neurologist."
For more information please see "Recent News" on MSAA's website at www.msaa.com, or call MSAA at (800) 532-7667.
Important Findings Presented
To follow are highlights from some of the educational and poster sessions given at the American Academy of Neurology's Annual Meeting held earlier this year. This is a continuation of the cover story on the same topic in the Summer 2005 issue of The Motivator. As space allows, additional summaries may appear in future issues.
- Interferons and Pregnancy Over the course of eight studies with 3,361 women and 69 pregnancies, interferon beta-1a administration is still contraindicated and not recommended for women who are pregnant or are trying to become pregnant. While the majority of pregnancies have the potential to go full-term and deliver a healthy baby, this report showed a higher incidence of lost pregnancies (when receiving interferon within two weeks or less of conception). Until more data is available, patients are "strongly advised" to stop interferon treatment prior to becoming pregnant.
- MRI as an indicator of continued disease activity Through the OPTIMS multi-center trial, investigators concluded that a single active MRI scan after six months treatment is the best indicator of persistent disease activity in those treated with Betaseron. They found that a patient with an active scan at six months will probably remain active for the entire first year of treatment, and such patients should be considered for a change in treatment, such as an adjustment in dose or drug selected. Increasing the dose of Betaseron by 50 percent led to a dramatic decrease in this MRI activity. (Readers are cautioned not to alter their treatment or dose unless under the guidance of their physician.)
- Treatments delay progression of MS A French observational study of 1,609 individuals with RRMS suggests that disease-modifying treatments begun prior to reaching any noticeable disability (having an EDSS of three or less) may delay the progression of long-term disability. The mean number of years for follow-up was 13, with some patients being followed for more than 20 years.
- Copaxone restores immune function A small study in Boston, Massachusetts was conducted to see how glatiramer acetate (Copaxone) affected CD4+ and CD25+ T-cells, which help to regulate the immune system. Researchers hypothesized that individuals with MS may have a loss in terms of frequency and/or function of these cells, which may contribute to a lack of immunoregulation observed in MS patients. Five of the seven MS patients in the study showed impaired function of these cells. Function was largely restored three months after beginning treatment with glatiramer acetate, indicating that this therapy may rapidly improve regulatory CD4+ and CD25+ T-cell function early in the course of treatment.
- New treatment for PBA A study was conducted to assess the safety and efficacy of AVP-923 (Dextromethophan/ Quinidine) for the treatment of pseudobulbar affect (PBA) in MS patients. PBA is associated with some neurological disorders and is characterized by uncontrolled episodes of laughing and crying. Study results indicate that AVP-923 is safe, well-tolerated, and highly effective in treating individuals with MS who experience PBA.
- Oral MS treatment trial encouraging An open-label study was conducted to evaluate the safety and effectiveness of oral fumaric acid in patients with RRMS. This drug is presently used for psoriasis, which may have a similar inflammation process to MS. The drug is thought to suppress inflammation by promoting Th2-type cytokine profile (a chemical produced in the body that works to suppress inflammation). According to the researchers of this study, oral fumaric acid significantly reduced the number and volume of gd-enhancing lesions in MS patients during the 70 weeks (approx. one year and four months) of treatment; all patients in the trial remained clinically stable. No adverse events were reported. These findings demonstrate that further studies of oral fumaric acid in the treatment of MS are warranted.
- Bone marrow transplants help six patients A three-year follow-up of a Canadian phase II trial using bone marrow transplantation showed clinical stabilization or improvements in the six patients who participated. These patients had aggressive MS and each underwent immunoablation (a complete eradication of the immune system to halt ongoing MS immune-mediated damage) followed by autologous (self) stem-cell (bone-marrow derived) transplantation. Those patients who experienced improvement had increased visual and motor capabilities. MRI studies failed to detect any new disease activity in any of the patients.
- Ginkgo biloba may improve attention In a pilot study, ginkgo biloba was given to individuals with MS experiencing cognitive dysfunction. Participants received either 120 mg of ginkgo biloba twice daily, or a placebo, for 12 weeks. Results suggest that ginkgo biloba may be effective in improving attention for those with cognitive dysfunction as a result of MS. More studies are needed to confirm this finding.
- Methotrexate may help progressive MS An open-label, 18-month, phase I trial of the intrathecal administration (injection directly into the spinal fluid) of methotrexate (ITMTX) was conducted with 100 patients who had severe MS. Looking at safety and tolerability as the primary objective, and efficacy as a secondary objective, the trial enrolled 74 participants with RRMS or SPMS and 26 with PPMS. Each received a minimum of two pulsed doses via lumbar puncture; most received four doses. Results indicated that the treatment was well tolerated and safe; no one discontinued treatments due to side effects; and 96 percent of the patients stabilized or improved in terms of their EDSS scores. Four patients, all with PPMS, continued to worsen in their EDSS scores. No MRI studies were mentioned. Phase II, double-blind studies are needed to confirm the safety, tolerability, and efficacy of ITMTX.
