Alice Melão, MSc,  —

Articles by Alice Melão

May 2, 2018 News by Alice Melão, MSc

#AAN2018 — Lemtrada Sustains Long-Term Benefits for RRMS Patients, TOPAZ Study Shows

Lemtrada (alemtuzumab) can sustain reduced activity and prevent progression of relapsing-remitting multiple sclerosis (RRMS) for more than seven years, clinical data from the CARE-MS extension trial shows. Findings were recently presented in four poster presentations at the 2018 Annual Meeting of the American Academy of Neurology (AAN) in Los Angeles. Lemtrada, marketed by Sanofi Genzyme, is an approved MS therapy that, according to its label, should generally be reserved for patients who have had an inadequate response to two or more other therapies. But the use of the word "generally" opens a window of opportunity “to use Lemtrada as a second-line therapy and potentially first-line therapy,” Barry Singer, MD, director of the MS Center for Innovations in Care at Missouri Baptist Medical Center, said in an email response to questions from Multiple Sclerosis News Today. The treatment was initially tested in two pivotal clinical trials in comparison with a high-dose under-the-skin injection of Rebif (interferon beta-1a) in RRMS patients. Participants were either new to treatment (CARE-MS I, NCT00530348) or had not responded to prior therapies (CARE-MS II, NCT00548405). During these trials, patients received 12 mg of Lemtrada for three or five consecutive days in two annual courses — at the beginning of the study and again one year later. After completing this treatment period, they had the opportunity to participate in a four-year extension study (NCT00930553) during which they could receive the therapy as needed to control their disease. Patients completing the extension could enroll in the five-year TOPAZ trial (NCT02255656) for further evaluation. To date, 80% of the participants (299 patients) from CARE-MS I and 73% from CARE-MS II (317 patients) have completed seven years of long-term follow-up. After completing two initial courses of Lemtrada, 59% of patients from CARE-MS I and 47% from CARE-MS II did not require additional treatment courses with Lemtrada or other disease-modifying therapies during the next six years. Two-thirds of  CARE-MS II patients who required a third Lemtrada course also experienced disability stabilization one year after the last treatment. During the seven years of follow-up, reported annualized relapse rates remained low, and 37% of patients from CARE-MS 1 and 44% from CARE-MS II experienced confirmed improvements in disability. In fact, during this period, only 26% from CARE-MS 1 and 31% from CARE-MS II showed disability worsening. The treatment also had a sustained effect on slowing brain volume loss by the seventh year, with a median yearly brain volume loss of 0.20% or less from the third to seventh year. This effect was found to be even better than that reported during the initial two years of treatment in the pivotal studies (0.59% in the first year and 0.25% in the second year in CARE-MS I, and 0.48% in year one and 0.22% in year two in CARE-MS II). Additionally, evaluation by magnetic resonance imaging (MRI) showed no signs of disease activity during the seven years of follow-up. “The extension study data being presented at AAN illustrate that more than two-thirds of patients did not experience confirmed disability worsening at year seven after initiating treatment with Lemtrada,” Singer said in a press release. “In addition, consistent effects were maintained over time across relapses and MRI outcomes including brain volume loss, even though the majority of patients did not receive any additional treatment over the prior six years.” During the extension studies, the frequency of adverse events was similar to that reported during the pivotal studies. In seven years, three deaths occurred, none of which was considered to be treatment-related. Thyroid adverse events were reported to be more frequent by the third year, but declined thereafter. As Singer noted, "the serious risks of Lemtrada, including serious infusion reactions, serious infections, thyroid disease, kidney disease, low platelets and potential malignancies, must always be discussed with the patient." All patients should also be carefully monitored on a monthly basis for four years after the last treatment course “to screen for autoimmune complications, including low platelet counts, thyroid disease, and kidney disease,” he said. Lemtrada’s long-term effects were shared at the AAN annual meeting in these presentations: “Active RRMS Patients Treated with Alemtuzumab Experience Durable Reductions in MRI Disease Activity and Slowing of Brain Volume Loss: 7-Year Follow-up of CARE-MS II Patients (TOPAZ Study)” “Durable Clinical Outcomes With Alemtuzumab in Patients With Active RRMS in the Absence of Continuous Treatment: 7-Year Follow-up of CARE-MS II Patients (TOPAZ Study)” “Durable Reduction in MRI Disease Activity and Slowing of Brain Volume Loss in Alemtuzumab-Treated Patients With Active RRMS: 7-Year Follow-up of CARE-MS I Patients (TOPAZ Study)” “Durable Clinical Efficacy of Alemtuzumab in Patients With Active RRMS in the Absence of Continuous Treatment: 7-Year Follow-up of CARE-MS I Patients (TOPAZ Study) Lemtrada is approved in more than 60 countries, and has additional marketing applications under review by regulatory authorities worldwide.

April 27, 2018 News by Alice Melão, MSc

#AAN2018 – Stem Cell Transplant is Effective Treatment for ‘Aggressive’ MS, Study Shows

Autologous hematopoietic stem cell transplantation, also known as aHSCT, has been shown to be safe and highly effective to treat patients with "aggressive" multiple sclerosis. Tested in 19 patients, transplantation of stem cells was found to induce clinically meaningful improvements in disability. These findings were shared at the 2018 Annual Meeting of the American Academy of Neurology (AAN) in Los Angeles, California. aHSCT uses a patient’s own healthy bone marrow stem cells, in combination with a much less aggressive chemotherapy and/or radiation regimen, to prepare the patient for the transplant. Previous studies have suggested that aHSCT is an effective strategy to treat patients with highly active relapsing-remitting MS (RRMS) who do not respond to available disease-modifying therapies (DMTs), and international guidelines advocate for its use in patients with "aggressive" MS. To further demonstrate the potential of aHSCT as a treatment for "aggressive" MS, a research team evaluated its safety and effectiveness in MS patients who had not been treated previously with DMTs. A total of 19 patients were treated across several clinical centers: seven patients were from Sheffield, U.K., seven from Uppsala, Sweden, four from Ottawa, Canada, and one patient was from Florence, Italy. All patients received aHSCT between May 2004 and May 2017. In addition to aHSCT, patients were treated with BEAM (carmustine, etoposide, cytarabine, melphalan) chemotherapy plus antithymocyte globulin (ATG) to reduce transplant rejection, or with Cytoxan (cyclophosphamide) with ATG, or the triple combination of Cytoxan, ATG, plus busulfan as conditioning regimens. Patients had a median age of 33 years at diagnosis and received the aHSCT by a median time of nine years after symptom onset. They had a median disability score of 6.5 before the treatment, as determined by the Expanded Disability Status Scale (EDSS). After a median follow-up period of 30 months, patients had a median EDSS score of 2.0, which represented a median improvement of 2 points (the higher the score, the worse the patient's disability level). None of the patients had clinical relapse following the transplant of stem cells. Only three patients developed new brain lesions detectable by magnetic resonance imaging (MRI) at the first six-month follow-up evaluation, but no additional new lesions were detected in the following scans. The adverse effects reported during the study were comparable to those previously observed in similar treatments. No deaths related to the treatment were reported. Based on these preliminary results, the researchers concluded that aHSCT is “safe and highly effective in inducing rapid and sustain remission” in highly active MS, and "was associated with a significant improvement of [patient’s] level of disability.” “aHSCT should be considered as first line therapy in patients with ‘aggressive’ MS,” the team concluded. Another study presented at the AAN 2018 meeting further supports these findings, demonstrating the superior effectiveness of aHSCT over conventional DMTs for RRMS.

March 14, 2018 News by Alice Melão, MSc

National MS Society to Award $433,800 to Support 10 Pilot Research Projects

The National Multiple Sclerosis Society will award $433,800 to 10 high-risk pilot studies that will quickly evaluate new strategies and interventions and enhance knowledge about multiple sclerosis (MS). According to a press release, the award winners will address different aspects of the disease, including potential treatments for fatigue and loneliness, to improve patients' walking abilities, and a strategy to change gut bacteria effects in MS. The year-long Pilot Research Grant program is a way to support early-stage research projects to quickly test their effectiveness. The MS Society also said that additional projects will be awarded this year. Results of a recent survey of approximately 300 pilot grant recipients revealed the program successfully promotes new ideas and brings new researchers to the MS field. About 90 percent of the respondents agreed that the financial support was very important for their research project. In 85 percent of cases, the grant supported new ideas, and in 56 percent it allowed support for additional grants. These pilot grants allow researchers to obtain preliminary data so they can decide to apply for additional funding, if the project looks  promising, or to put the idea to rest.

 

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