By: Nityanand C, Data Analyst, Aissel Solutions
Alemtuzumab is a licensed monoclonal antibody for the treatment of chronic lymphocytic leukemia. It has been put under evaluation since the day it has shown the ability to treat one of the complex neurological diseases like Multiple Sclerosis. Clinical trial results announced till date including the one presented recently at the 63rd Annual Meeting of the American Academy of Neurology held in Hawaii have been very appreciative. Will it really meet the unmet needs of treating MS??
Multiple Sclerosis is an inflammatory, auto immune and also one of the most commonly occurring neurological disorders which majorly affects the Central Nervous System. Destruction of the myelin sheath around the nerve cells (axons) of the brain and spinal cord by T-cells of the immune system affects the nerve cells’ ability to communicate with each other, which eventually affects body’s normal response to stimuli function. The disease onset usually occurs in young adults and is more common in women. The symptoms of this disorder are unpredictable and vary greatly between individuals depending on the site of inflammation and often progress to Cognitive Disability. Impaired Vision, Loss of Muscle Coordination and Mood Swings are few of the commonly observed symptoms. Though much about the disease is known specific causes for the disease are yet to be understood. Mutations, Environmental factors and Infections are identified as some of the causes.
MS is often referred by “Diagnosis Exclusion” title, as none of the thousands of diagnosis methods can clearly identify it, except that MRI scanning can highlight the inflamed sites in the brain. Hence diagnosis of MS typically takes a period of time and depends on over all symptoms and subject’s medical history. MS usually appears with different types of patterns of progression which have been recognized as subtypes of MS. Relapsing - Remitting MS (RRMS) and Secondary Progressive MS(SPMS) are the most commonly observed and severe types. According to National Multiple Sclerosis Society’s statistical analysis more than two million people are suffering from MS worldwide. Though there are several preventive treatments available for MS, lack of precise diagnosis methods to identify the root cause and difficulty in prognosis might have become the most complex barriers to invade through and explore “cure” for MS. The disease has been titled as non-fatal but living with physical and cognitive disability can never be better than fatalness. Hence there is an evident need of a cure to MS, otherwise a much competent preventive treatment than the existing ones.
Alemtuzumab (marketed as Campath, MabCampath or Campath-1H), used in the treatment of Chronic Lymphocytic Leukemia and T-cell Lymphoma, is a humanized monoclonal antibody, targets CD52 protein (present on T-cells) associated with lymphoma. This potential of inhibiting or killing T-cells has made Alemtuzumab significant in treating MS because destruction of the myelin sheath by auto immune T-cells can be prevented. Therefore it has been put on several clinical trials to comprehensively understand its efficacy and safety in treating MS.
Alemtuzumab was initially tested for both Relapsing – Remitting and Secondary Progressive MS in earlier trials and it was found that the drug has more consistent result in reducing the number of relapses and improving the disability in RRMS subjects and mixed result in SPMS subjects. There was also a significant improvement in disability of RRMS subjects up to 3 years after the treatment.[1] These impressive results further led to Phase II trial whose objective was set to determine the effectiveness of different doses of Alemtuzumab at early stage of disease onset and also to compare it with existing approved therapy like interferon beta-1a (Rebif). In the trial 334 patients with early active Relapsing-Remitting MS were randomized to treatment with Alemtuzumab at one of two dose levels (12mg or 24mg per day) or to the approved MS therapy Rebif. The results of the trial declared Alemtuzumab most effective than interferon beta-1a in reducing the rate of sustained accumulation of disability and rate of relapse.[2]
Alemtuzumab has now revivified the curiosity it has created earlier after successfully completing a three year follow up study and making analysts across the globe to predict its peak annual sales. Genzyme presented some of the important results of the follow up study at the 63rd Annual Meeting of the American Academy of Neurology in Hawaii, held on April 9 - 16, 2011. One of the abstracts presented by Laura Balcer MD, Associate Professor of Neurology, University of Pennsylvania School of Medicine caught the pharma world’s attention as it displayed the ability of Alemtuzumab to increase the visual contrast sensitivity of the MS subjects. Visual impairment is one of the commonly observed and unaddressed issues by currently available therapies. The overall results of the follow up study concluded that MS subjects treated with Alemtuzumab were both free of relapse and sustained increase in disability.
Alemtuzumab has been appreciated for its potentiality but safety issues which had come up during earlier trials are yet to be addressed. Two of the currently ongoing Phase III studies CARE-MS I [3] and CARE-MS II [4] (Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis I and II) are evaluating both safety and efficacy of different doses in comparison to the existing approved therapies. The trials are expected to provide primary results by the end of second quarter of this year. Genzyme which has already bagged Fast Track tag for Alemtuzumab by FDA is on toes to put marketing application by 2012 if Phase III results are as good as earlier trials.
[1] Journal of Neurology; Vol. 253; Jan 2006
[2] New England Journal of Medicine; Vol. 359 (17); Oct 2008
[3] ClinicalTrials.gov No. NCT00530348
[4] ClinicalTrials.gov No. NCT00548405
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