The Huntington's
Scene In New Zealand |
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| Articles taken from the Sept. 2003 Huntington's News. The Quarterly Newsletter of the Huntington's Disease Associations of New Zealand |
Encouraging Preliminary Results about LAX 101
By Shawn Mitchell, Director of Communications and Volunteer Development,
Huntington Society of Canada, (with source information from Amarin Corporation pie and the
Web site for the Huntington Study Group at www.huntington-study-group. org
In October 2002, Amarin Corporation, the company responsible for the development of LAX-101, produced a public disclosure of the preliminary results of a Phase III study of LAX-101, an experimental drug being developed for treating patients with Huntington’s disease (HD).
What is a Phase III study?
In a Phase III study, an experimental drug is tested in a hundred to several thousand patients with the disease/ condition of interest. The large-scale testing provides the pharmaceutical company as well as the U.S. Food and Drug Administration (PDA) with a more thorough understanding of the drug’s effectiveness, benefits/risks, and range/ severity of possible negative side effects. Most Phase III studies are randomized, and Phase III studies typically last several years. Seventy to 90 percent of drugs that enter Phase III studies successfully complete this phase of testing.
The Amarin press release announced the preliminary results on a multi-centre, double-blind, randomized, placebo-controlled study of LAX-101 , which enrolled 135 patients with HD at six sites located in the United States, Canada, U.K. and Australia. Drs. Blair Leavitt and Michael Hayden, who are both NAVIGATOR Coalition investigators, were responsible for the LAX-101 trial that was run in Vancouver, BC. In general, these results are also consistent with findings in Phase II studies previously reported in January 2002.
What is a multi-centre, double-blind, randomized, placebo-controlled study?
First, multi-centre means that the trial was conducted in more than one place. In this instance, the drug was tested on patients in six different locations.
Second, double-blind, randomized, placebo-controlled means that one group of patients receives the experimental drug, while a second or control group receives a placebo (often a pill that contains sugar or just water). Whether a patient receives the drug or the placebo is decided by random chance (as if by the flip of a coin). Lastly, double-blind means that no one (the patient or the researcher studying the patient) actually knows who is getting the experimental drug or the placebo.
The primary end-point in the first 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 HD. While trends favoured LAX-101 over placebo, statistical significance was not reached when measured in the intent-to-treat population (all patients entering the study, including those who dropped out or did not comply with the protocol). Significant results were achieved in the subset of patients evaluated (those completing the study in compliance with protocol requirements). The study also produced trends in favour of LAX- 101 in several secondary endpoints.
What is a UHDRS score?
UHDRS stands for Unified Huntington’s Disease Rating Scale. The UHDRS is a research tool that has been developed by the Huntington Study Group (HSG). The purpose of the scale is to allow the researchers to grade the symptoms of HD in a way that allows them to make accurate comparisons between individual patients, and to better chart the course of the disease in patients. The scale is divided into a number of different subscales, including the Total Motor Score 4 (TMS-4).
In a study like this one, each patient will start the drug trial with a set of UHDRS scores that puts their symptoms into a number form. Then, during the course of the drug trial, all the study participants will be periodically re-evaluated to see if their UHDRS scores have changed. Researchers know that the UHDRS scores of patients with HD will change over time as their symptoms change.
The primary end-points (the most important thing where you hope/ expect to see some amount of change) of the LAX-101 trial are a change over a one year period in the Total Motor Score 4 (TMS-4) sub-scale of the UHDRS.
The pre-determined end-points of the trial (such as UHDRS scores) are compared for the patients on drugs and the patients on placebos. If there are significant differences between the scores then it’s possible that the drug can be said to have had some kind of impact on Huntington’s disease.
LAX-101 was found to be well tolerated by patients throughout the trial. The incidence and types of adverse reactions that occurred were similar in the placebo and drug groups.
After meetings with representatives from the Food and Drug Administration (PDA), Amarin Corporation pie and Laxdale Ltd announced on February 3, 2003 their intention to conduct an additional Phase III study for LAX-101. Rick Stewart, CEO of Amarin Corporation, stated, “The decision to conduct a second Phase III study is consistent with the approval process of new drug products for neurological disease, and reflects the fact that statistical significance was not achieved in the intent to treat patient population in the first Phase III study. We were encouraged by the results of our previously announced Phase III trial, and look forward to finalizing our protocol with the FDA for our second Phase III trial.”
Amarin Corporation pie is a specialty pharmaceutical company focused on neurology and pain management. The company plans to become a leader in these therapeutic categories by providing innovative products and solutions that address significant unmet medical needs.
Acknowledgement: “Horizon”, Huntington Society of Canada. No 108,
Spring 2003