West Coast Editor
Just more than a year after reporting that the company's drug for Huntington's disease worked in a subset of patients, Amarin Corp. plc has reached an agreement with the FDA for a special protocol assessment under which two pivotal Phase III trials will be conducted.
"The first is in the U.S. in 300 patients, and in the autumn we begin the European trial with 240," said Alan Cooke, chief financial officer of London-based Amarin. Data should be available near the end of next year, added Cooke, speaking from the company's Dublin, Ireland, branch.
Amarin's stock (NASDAQ:AMRN) closed Monday at $1.51, up 9 cents.
Granted fast-track status, the compound is Miraxion, a semi-synthetic, highly purified derivative of (all-cis)-5,8,11,14,17-eicosapentaenoic acid, which works by stabilizing cell membranes and mitochondrial integrity of neurons, thus preventing or slowing progression from neuronal dysfunction to apoptosis.
In the summer of 2004, Amarin said gene variant data from a failed Phase III trial showed that a group of participants did benefit, as measured after one year by the Total Motor Score-4 score of the Unified Huntington's disease rating scale. (See BioWorld Today, Aug. 25, 2004.)
"It's basically mild to moderate patients, which make up about 70 percent of the total," Cooke said, noting that the earlier Phase III trial was an "all comers" study.
In both of the new trials, the primary endpoint will be to determine whether Miraxion taken at a 1-gram dose two times daily brings clinically and statistically significant changes, determined by the same measures as before.
Huntington's disease, characterized by movement disorder, dementia and psychiatric disturbance, has been diagnosed in about 30,000 patients in the U.S. and a similar number in Europe. More than 200,000 people in the U.S. are known to be genetically "at risk" for developing the disease.
Onset of symptoms is typically between 30 years and 50 years of age with a typical life expectancy from diagnosis of 10 years to 25 years, and patients with late-stage disease need continuous nursing care, often in nursing homes. The potential market in North America and Europe is estimated to be more than $500 million per year.
No drug is approved for the condition, and "there's really nothing in late-stage development" other than Miraxion, Cooke said.
This spring, Washington-based Prestwick Pharmaceuticals Inc. submitted a new drug application for tetrabenazine in chorea, which is one motor symptom associated with Huntington's disease. Approved outside the U.S. under the brand names Xenazine in Europe and Nitoman in Canada, the compound is a selective and reversible dopamine depletor designed to work by inhibiting vesicular monoamine transporter 2. (See BioWorld Today, April 26, 2005.)
"A lot of different drugs have been tested in the disease over time, but they haven't shown efficacy," Cooke said, and the sub-group analysis from the earlier Phase III study by Amarin "gives us good confidence that this second set of trials will work."
Amarin gained full ownership of Miraxion through the October 2004 buyout of privately held Laxdale Ltd., of Stirling, Scotland, though Amarin had licensed U.S. rights in November 2000.
"Early on, after we acquired Laxdale, a lot of investors really valued the SPA, so we started going down that path with the FDA," Cooke told BioWorld Today, pointing out that "trials can get complicated" in conditions such as Huntington's.
The Huntington Study Group, a non-profit group based at the University of Rochester, will conduct the U.S. trial on behalf of Amarin. In Europe, the trial will be done in collaboration with Euro-HD, also a non-profit group, and the contract research organization ICON plc, based in Dublin.