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Gene Variant Data Analysis Identifies Patients Who Responded to Miraxion in Phase 3 Trial
LONDON, August 24 /PRNewswire-FirstCall/ -- Amarin Corporation plc (NASDAQSC: AMRN) today announced the results of a gene variant data analysis from the initial Phase III clinical trial for Miraxion™ (formerly referred to as LAX-101) in Huntington's disease. The analysis identifies a group of patients with a specific gene variant that experienced a significant response to Miraxion™. The initial twelve month, phase III multi-center, double blind, randomized placebo controlled study of Miraxion™ was conducted in 2002 by Laxdale Limited ("Laxdale") with 135 enrolled patients with Huntington's disease at six centers in the United States, Canada, the United Kingdom and Australia. The primary endpoint in the initial trial was the change over a one-year period in the Total Motor Score-4 (TMS-4) subscale of the Unified Huntington's Disease Rating Scale (UHDRS), the standard rating scale for trials in this disease.
The additional data analysis identifies a group of participants in the initial study for whom Miraxion™ showed a significant clinical benefit. Huntington's disease is believed to be caused by a genetic mutation of the cytosine, adenosine and guanine (CAG) polymorphic trinucleotide repeat. It is believed that there is a direct link between CAG repeat length and age of onset, disease progression and clinical symptoms of Huntington's disease. CAG repeat length can be measured via a genetic blood test.
Efficacy of Miraxion™
The possibility that treatment efficacy of Miraxion™ could be related to the number of CAG repeats was proposed as part of the pre-specified analysis and exploratory analysis was conducted after completion of the trial to examine this influence. A strong correlation between the CAG repeat number and the change in TMS-4 score was revealed in those patients taking Miraxion™. In order to explore this effect further, patients were split into two groups based around the median number of CAG repeats, which was identified as 45. Those patients that took Miraxion™ and had a CAG repeat length of less than 45 comprised the responsive group. This effect was consistent across all centers. In total, 67 of the 135 patients in the initial phase III study had this specific gene variant. It is estimated that patients with a CAG repeat length of less than 45 represent over 65% of all Huntington's disease patients.
The group of patients with a CAG repeat length of less than 45 in the intent to treat group receiving Miraxion™ showed a statistically significant improvement over those patients receiving placebo (p=0.029, n=67). In the group of patients with a CAG repeat length of less than 45 who observed the clinical trial protocol (per protocol patients) receiving Miraxion™ showed a 22.7% improvement in TMS-4 score versus patients receving placebo who showed a 5.7% deterioration at the end of the twelve month study (p=0.006, n=44). This improvement was observed over a 6-month period and maintained for a further 6 months. In the 12-month open label continuation phase of the trial, this improvement continued to be maintained. At the end of the open-label phase all patients who had taken part in the trial were offered compassionate supply. More than 3 years after the commencement of this trial, 101 of the 135 patients enrolled in the trial continue to be supplied Miraxion™.
Rick Stewart, Chief Executive Officer of Amarin commented, "This data analysis, showing significant clinical benefit to specific patients taking Miraxion™, will be an important component in the design of the planned phase III clinical trials. It will allow us to more accurately target patients with this specific gene variant, particularly relating to age of onset of the disease. Improvement and stability are particularly beneficial if initiated at an early stage in this devastating disease. This could significantly extend a patient's professional activities, maintain a good quality of life, and potentially defer the onset of the later stages of the disease."
Planned Phase III Trials
Amarin intends to commence two phase III clinical trials totaling over 400 Huntington's disease patients in early 2005, subject to consummation of Amarin's proposed acquisition of Laxdale and the completion of an equity fund raising.
Miraxion™ has been granted Fast Track designation for Huntington's disease by the United States Food and Drug Administration and received Orphan Drug designation both in the U.S. and in Europe. Miraxion™ is also in clinical development for depression.
Huntington's disease is a genetic neurodegenerative disease characterized by movement disorder, dementia and psychiatric disturbance. It has been diagnosed in approximately 30,000 patients in the U.S. with a similar number in Europe. Additionally, over 200,000 persons in the U.S. alone are genetically "at risk" to developing the disease. Onset of symptoms is typically between 30-50 years of age with a typical life expectancy from diagnosis of 10-25 years. Patients with late stage disease require continuous nursing care, often in nursing homes, with an estimated annual cost to the U.S. economy of up to $2.5 billion. Presently, there is no effective treatment or cure for HD.