Unlike the bread mold Penicillium, fish oil supplements are available in commercially pure and assayed form.

LAX-101 bears the same sort of relationship to fish oil as does pure vitamin C to oranges, in the sense that LAX-101 and vitamin C each represent a purified, refined and tested pharmaceutical product derived from a natural source.

Laxdale has developed and proven a prescription drug to treat HD. With FDA approval this will enable medical workers and insurance companies to bring treatment to suffers of HD. This is great news for the HD community. See EPA sources. --Jerry

Posted to HDLighthouse: 04 Nov 2002 20:42 HDL Update: LAX-101 AND HUNTINGTON'S DISEASE: QUESTIONS AND ANSWERS

First Drug Treatment For HD "LAX-101 is the first product to show any statistically significant positive effect in HD in a study of this size."--Crispin Bennett PhD, Research Information Manager, Laxdale

From Crispin Bennett PhD, Research Information Manager, Laxdale

Please find attached Questions and Answers regarding LAX-101 and Huntington's Disease. Please post this on the HD Lighthouse website.

I trust that your readers will find this document to be useful and that it will answer any questions that they may have. Laxdale would like to thank you for your support and look forward to working with you in the future.

Best wishes
Crispin

What is LAX-101 ?
LAX-101 is an ultra pure, semi-synthetic derivative of a substance normally found in small amounts in the human body. LAX-101 is currently available only through the Laxdale clinical study program and is not available commercially. As befits a pharmaceutical product, the manufacture of this product is to the highest standards and it is not available from any company other than from Laxdale Ltd.

Why conduct a clinical study with LAX-101 in HD ?
The FDA, which regulates medical treatments in the USA, require controlled clinical studies (usually placebo-controlled) to show that a product is effective in treating an illness. Equivalent organizations in other countries also require such clinical studies. These regulatory agencies assess the results of clinical trials, and based on the results, grant approval for use. Regulatory approval is absolutely required before a product can be marketed.

What were the details of the pivotal study?
The pivotal study of LAX-101 in HD was a multicentre, double-blind, randomized, placebo-controlled study which enrolled 135 HD patients at a total of 6 sites in the U.S., Canada, the U.K and Australia. Each patient was assigned to receive either LAX-101 or an inactive placebo for 12 months. Neither doctor nor patient knew who was on what treatment, which is why the study was called "double-blind". The aim of this design, which is required by the FDA, and other government regulators, is to reduce bias. At the end of the study each patient was given the option of receiving LAX-101 for a further 12 months.

Progression of HD was measured in the study using standard rating scales in this disease, particularly the Unified Huntington's Disease Rating Scale (UHDRS).

What are rating scales?
Rating scales such as the Unified Huntington's Disease Rating Scale (UHDRS) are standardized procedures utilizing interviews, questions and tests which are designed to measure changes in the degree of illness over a period of time. The UHDRS also has sub-scales which measure changes in cognitive function, movements, functional capacity and independence.

What is an endpoint?
When designing a clinical study, the main objective must be identified in advance. This is called the primary endpoint (or primary variable). In the pivotal study of LAX-101 in HD, the primary endpoint was the change in the Total Motor Score 4 (TMS-4), a subscale of the UHDRS, over a one-year period. The TMS-4 is a reliable measure of the movement problems which occur in HD. As patients and their families know, the movement problems are a major issue because they make it difficult for patients to be employed, to be comfortable in social situations and to do normal tasks at home. An effect on the TMS-4 therefore indicates an important impact on the illness. Also when designing a study other important measurements are also identified. These become what are known as secondary endpoints.

What is the status of the pivotal study of LAX-101 in HD?
The initial 12-month double-blind, randomized, placebo-controlled part of the study is complete. Those patients who chose to enter the additional 12-month trial have now entered the follow-up period in which they all receive LAX-101. The overwhelming majority of patients chose to take LAX 101 for the additional 12-month period. Results from this follow -up study will be announced once it is complete.

What were the results of the pivotal study?
In patients who completed the study and who were compliant with the study protocol (the per-protocol group), preliminary results indicate that LAX-101 showed a statistically significant benefit on the TMS-4 subscale as compared to placebo. In addition, trends were in favour of LAX-101 in a majority of secondary endpoints, including total UHDRS score. The selection of per-protocol patients is made before the study is unblinded, so no bias can creep in.

When we look at the results of the intent-to-treat group (all patients entering the study, including those who dropped out or did not comply with the protocol), preliminary results indicate that patients allocated to LAX-101 did better than those on placebo, although the differences are not statistically significant.

What is the importance of statistical significance?
Statistical significance is the accepted means by which you state that these differences are real and not just chance. Whether these differences are clinically significant is a question that Laxdale will discuss with the FDA and equivalent organisations in other countries.

LAX-101 is the first product to show any statistically significant positive effect in HD in a study of this size.

Does LAX-101 reverse HD?
This study on LAX-101 was not specifically designed to answer this question. This is something Laxdale may want to look at in the future.

Does LAX-101 work in all HD patients?
Unfortunately, there is rarely a treatment that works in all patients with a specific disease. Again, Laxdale may conduct additional studies in the future to look at improving the actions of LAX-101.

Does LAX-101 work in all stages of HD?
The study looked at symptomatic patients with intermediate HD only. An earlier small study showed some benefits from LAX-101 in patients at a later stage of the disease.

Will LAX-101 stop me from developing HD symptoms if I am currently showing no signs of the disease?
The current study was not designed to answer this question. This is something Laxdale may want to look at in the future.

When will study results be available?
The scientific details of the pivotal study will be presented at an appropriate medical meeting once the study analysis is complete and will also be submitted for publication in a medical journal.

When will LAX-101 be available?
LAX-101 will be made available if it is approved by the FDA in the US, or equivalent regulatory authorities in other countries. Laxdale will be discussing the study results with the FDA, and equivalent organisations in other countries, in the near future. Laxdale can make no predictions about the timing or the outcome of this process.

Can I get LAX-101 through a compassionate-use program?
Not at present.

What will happen to patients that are currently on LAX-101 because they participated in the clinical study?
Laxdale will continue to supply LAX-101 to all HD patients currently receiving LAX-101 through the clinical trial program who wish to continue to take it at the end of the open-label part of the study.

Does LAX-101 have any side effects?
LAX-101 appears to have a good safety profile and is well tolerated by patients. The incidence and types of adverse events, including Serious Adverse Events (SAEs), reported in the study were similar in both placebo and active drug groups and are those expected in a study of this type. The most common reported side effect is stomach upset and diarrhea, but this is usually transient and not a major issue for the great majority of patients.

Can I take fish oil to treat HD
HD patients and families should note that fish oils have not been studied nor have they shown efficacy in Huntington's disease. Fish oils vary enormously in their composition. Fish oils may not be beneficial and, without testing, a harmful effect cannot be ruled out. LAX-101 bears the same sort of relationship to fish oil as does the antibiotic penicillin to the bread mould Penicillium, in the sense that LAX-101 and penicillin each represent a purified, refined and tested pharmaceutical product derived from a natural source.

Source: E-mail from Crispin Bennett PhD, Research Information Manager, Laxdale 04 Nov 2002

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