12 YR STUDY: 60% of MSers stabilized or improved on Alemtuzumab (Lemtrada)

[ActiveMSers]

This drug is too powerful not to get approved in the United States. There are significant secondary autoimmunity issues, but for someone with aggressive disease, this is as close to a rescue therapy as one will find. - Dave

Epub: Tuohy et al.

Alemtuzumab treatment of multiple sclerosis: long-term safety and efficacy.

]J Neurol Neurosurg Psychiatry. 2014 May 21. pii: jnnp-2014-307721. doi: 10.1136/jnnp-2014-307721.

OBJECTIVES: Alemtuzumab is a newly licensed treatment of active relapsing-remitting multiple sclerosis (RRMS) in Europe, which in phase II and III studies demonstrated superior efficacy over β-interferon in reducing disability progression over 2-3 years. In this observational cohort study, we sought to describe our longer-term experience of the efficacy and safety of alemtuzumab in active RRMS.

METHODS: Clinical and laboratory data including serial Expanded Disability Status Scale (EDSS) assessments, from all 87 MSers treated with alemtuzumab on investigator-led studies in Cambridge, UK, from 1999 to 2012, were collected. The occurrence of adverse events including secondary autoimmunity, malignancy and death, and pregnancy outcomes was recorded. Baseline variables including age, disease duration and relapse rate were compared in univariate and logistic regression analyses between groups with different disability outcomes.

RESULTS: Over a median 7-year follow-up (range 33-144 months), most MSers (52%) required just two cycles of alemtuzumab. In the remaining MSers, relapses triggered re-treatment to a total of three cycles (36%), four cycles (8%) or five cycles (1%). Using a 6-month sustained accumulation of disability definition, 59/87 (67.8%) of MSers had an improved or unchanged disability compared with baseline. By an area under the curve analysis, 52/87 (59.8%) MSers had an overall improvement or stabilisation of disability. Higher baseline relapse rate was associated with worse long-term disability outcomes, with trends for longer disease duration and older age at first treatment. Secondary autoimmunity was the most frequent adverse event occurring in 41/86 (47.7%) MSers, most commonly involving the thyroid gland.

CONCLUSIONS: Alemtuzumab is associated with disease stabilisation in the majority of MSers with highly active RRMS over an average seven-year follow-up. No new safety concerns arose over this extended follow-up.

[ActiveMSers]

Today the drug was resubmitted to the FDA for review. - Dave

Genzyme’s Lemtrada Resubmission Accepted for Review by FDA

Friday, May 30, 2014 2:15 am EDT

CAMBRIDGE, Mass.--(BUSINESS WIRE)--Genzyme, a Sanofi company (EURONEXT: SAN and NYSE: SNY), announced today that the U.S. Food and Drug Administration (FDA) has accepted for review the company’s resubmission of its supplemental Biologics License Application (sBLA) seeking approval of LemtradaTM (alemtuzumab) for the treatment of relapsing forms of multiple sclerosis. A six-month review period has been assigned for the Lemtrada sBLA. Genzyme expects FDA action on the sBLA in the fourth quarter.

This resubmission is based on data from the same clinical studies included in the original sBLA, and provides supplemental analyses and additional information to specifically address issues previously noted by the FDA in its December 27, 2013 Complete Response Letter. The company resubmitted the sBLA earlier this month following constructive discussions with the agency.

.- See more at: http://news.genzyme.com/press-releas....qG8B2uw5.dpuf

[ActiveMSers]

From ECTRIMS, the big Lemtrada news: slowing brain atrophy. - D

Alemtuzumab slows brain volume loss over 5 years in patients with active relapsing-remitting multiple sclerosis with most patients not receiving treatment for 4 years: CARE MS I and II extension study

F. Barkhof1, J.A. Cohen2, A.J. Coles3, D.A.S. Compston3, M. Filippi4, E.J. Fox5, G. Giovannoni6, H.-P. Hartung7, E. Havrdova8, S. Schippling9, K.W. Selmaj10, D.H. Margolin11, K. Thangavelu11, M.A. Panzara11, D.L. Arnold12,13, on behalf of the CARE-MS I and CARE-MS II Investigators
1VU University Medical Centre, Amsterdam, The Netherlands, 2Cleveland Clinic, Cleveland, OH, United States, 3University of Cambridge School of Clinical Medicine, Cambridge, United Kingdom, 4San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy, 5Central Texas Neurology Consultants, Round Rock, TX, United States, 6Queen Mary University of London, Barts and The London School of Medicine, London, United Kingdom, 7Heinrich-Heine University, Düsseldorf, Germany, 8First Medical Faculty, Charles University in Prague, Prague, Czech Republic, 9Neuroimmunology and Multiple Sclerosis Research, Department of Neurology, University Hospital Zurich and University of Zurich, Zurich, Switzerland, 10Medical University of Łódź, Łódź, Poland, 11Genzyme, a Sanofi company, Cambridge, MA, United States, 12NeuroRx Research, Montréal, QC, Canada, 13Montréal Neurological Institute, McGill University, Montréal, QC, Canada

Background: In two phase 3 trials in patients with active relapsing-remitting multiple sclerosis (RRMS), alemtuzumab had superior efficacy versus subcutaneous interferon beta-1a (SC IFNB-1a), including a significant slowing of brain volume (BV) loss over 2 years; in active treatment-naive patients in CARE-MS I (NCT00530348) by 42% and in patients who had an inadequate response (≥1 relapse) to a prior therapy, in CARE-MS II (NCT00548405) by 24%. Slowing of BV loss was durable through 4 years, despite most patients not receiving alemtuzumab retreatment since Month 12 or another disease-modifying therapy (DMT).

Goals: To examine alemtuzumab's effect on BV change over 5 years in patients who participated in the CARE-MS study program and ongoing extension study.

Methods: The CARE-MS studies enrolled patients with active RRMS (≥1 relapse in the past year and ≥2 in the past 2 years). Patients randomised to alemtuzumab received 2 annual courses of alemtuzumab 12 mg, at Month 0 and Month 12. In the extension study (NCT00930553), as-needed alemtuzumab retreatment was available based on evidence of disease activity (eg, relapse or magnetic resonance imaging [MRI] activity). Patients could receive another DMT at the investigator's discretion. MRI scans were acquired at baseline and annually thereafter. BV loss was measured by relative brain parenchymal fraction change.

Results: 349 (95%) CARE-MS I and 393 (93%) CARE-MS II alemtuzumab patients entered the extension study. Of those, 68% in CARE-MS I and 60% in CARE-MS II did not receive alemtuzumab treatment since Month 12, and 2% and 8% received another DMT. Median rate of BV loss decreased progressively over 4 years in CARE-MS I and remained low in Year 5 (Year 1: -0.59%, Year 2: -0.25%, Year 3: -0.19%, Year 4: -0.15%, Year 5: -0.20%). Median rate of BV loss progressively slowed over 3 years in CARE-MS II and remained low in Years 4 and 5 (Year 1: -0.48%, Year 2: -0.22%, Year 3: -0.10%, Year 4: -0.19%, Year 5: -0.07%).

Conclusion: Slowing of BV loss with alemtuzumab was maintained over 5 years in patients who were treatment-naive or had an inadequate response to prior therapy, despite most patients not receiving additional treatment over the previous 4 years. The durable effect on slowing BV loss may result from a reduction in inflammation and the immunomodulatory effects of the distinct pattern of lymphocyte repopulation following treatment with alemtuzumab, which represents a novel treatment approach for RRMS.