Care4Dystonia, Inc.

There recently has been increasing concern about the recent ? FDA and Black Box warnings regarding Botulinum Toxins Type A and B ( Botox and MyoBloc ). We have received many emails concerning the use of both Toxins and related reports that have been released by the group Public Citizens at www.citizens.org.

Please note the following information we received from Allergan, Inc. :

“The FDA announced on Friday ( 2-7-08)� in an “Early Communication” that it was reviewing certain serious adverse events following the use of botulinum toxins.� The FDA inquiry relates primarily to high dose medical uses of Botox, particularly for the management of juvenile cerebral palsy (see attached our press release� at www.allergan.com ).�

United States. Fortunately, the FDA’s Rusty Katz in the media teleconference was clear to point out that this review involves a small number of adverse event reports involving large doses in a very sick population and should not be interpreted as a suggestion that Botox is not an appropriate treatment for juvenile cerebral palsy.�

The treatment of juvenile cerebral palsy involves very compromised, sick children and it also involves relatively large doses of product (often up to a total of 700 units).� In some of these adverse event reports, the physician had used doses that were much higher than the approved label for juvenile cerebral palsy in those countries that have approved its use.� � � �

As the FDA’s own press release on the topic notes, these adverse event reports do not indicate any problem with a batch of Botox but rather may relate to overdosing by the physician.� Our analysis indicates that when a problem arises in the use of the product for juvenile cerebral palsy, it tends to either be because the patient was already very high risk and sick and/or because a significant amount of Botox was administered.� �

While not approved in the United States, we know that physicians specialized in neurological and neuromuscular disorders have been using Botox for the treatment of juvenile cerebral palsy /spasticity with great success for more than a decade at their own medical discretion; and most physicians who use Botox in this way are well aware of the risk/benefit profile in this population and use it after making an informed medical judgment that the treatment is appropriate.

Furthermore, the product labeling for BOTOX already notes rare select cases of fatal outcomes in which some patients had significant debilitating conditions or may have had a history of cardiovascular disease or other co-morbid conditions. And the BOTOX labels specifically warn that patients with pre-existing neuromuscular disorders may be at increased risk of clinically significant systemic effects from typical doses of BOTOX.� Allergan will discuss with the U.S. FDA whether further clarify about the definition of juvenile cerebral palsy as a “neuromuscular” disorder is needed in the U.S. Botox label, and make any appropriate changes, as needed, following the Agency’s conclusion. ” ~ Corporate Communications, Allergan, Inc.

Further Information :

Allergan, Inc. Responds to Public Citizen’s Allegation Regarding a Fatality Following BOTOX(R) Cosmetic Treatment� �

http://agn360.client.shareholder.com/releasedetail.cfm?ReleaseID=290197

http://agn360.client.shareholder.com/releasedetail.cfm?ReleaseID=290726

http://agn360.client.shareholder.com/releasedetail.cfm?ReleaseID=293012

http://www.solsticeneuro.com/news/Solstice_PR_2.08.08.html� regarding MyoBloc.�

Finally, it is equally as important to explain that a report of an adverse event following treatment with a drug does not by itself mean that the drug caused the event, just that the event occurred after treatment with the drug.� So, for instance, if Allergan is notified of an adverse event following Botox treatment from any source, it is required to make an “adverse event report” to the appropriate health authorities even if Allergan or the physician has not established that Botox caused the event and, indeed, even if the treating physician has affirmatively concluded that Botox was not the cause of the event. ~ J.E.� The above is required of any pharmaceutical company. Thus, Rest Assured, Remain Assured, Be Assured.

http://care4dystonia.org/index.php/2008/02/13/cd-and-beb-merz-trials/� Name of this Post.

A recent finding from UHN researchers Drs. Elena Moro, Andres Lozano, Janis Miyasaki, Anthony Lang, Jonathan Dostrovsky and William Hutchison may be a potential therapeutic treatment for individuals with cervical dystonia (CD) - a painful disorder characterized by the involuntary movement of neck muscles. Primary CD is estimated to affect approximately 20-40 individuals out of 100,000.The study followed CD patients who were previously unresponsive to medical treatment.� Participants underwent deep brain stimulation (DBS) of their bilateral globus pallidus internus.� DBS uses electrical stimulation to block neuronal signals that cause movement disorders (such as tremor, dystonia, stiffness and tics).

Results showed that this technique was an effective long-term therapy.� “This treatment is effective in improving severity, disability, and pain in patients with CD that is currently not adequately controlled by medication,” says Dr. Moro.� “The clinical benefit has proven stable over a two-year period; however, more studies are needed to determine the optical parameters of stimulation in patients with CD.”

The clinical testing of experimental drugs is normally done in three phases, each successive phase involving a larger number of people. Once the FDA has granted a New Drug Approval (NDA), pharmaceutical companies also conduct post marketing or late phase three/phase four studies.

A Phase One Study:

Phase I studies are primarily concerned with assessing the drug’s safety. This initial phase of testing in humans is done in a small number of healthy volunteers (20 to 100), who are usually paid for participating in the study. The study is designed to determine what happens to the drug in the human
body — how it is absorbed, metabolized, and excreted. A phase I study will investigate side effects that occur as dosage levels are increased. This initial phase of testing typically takes several months. About 70 percent of experimental drugs pass this initial phase of testing.

A Phase Two Study:

Once a drug has been shown to be safe, it must be tested for efficacy. This second phase of testing may last from several months to two years, and involve up to several hundred patients. Most phase II studies are randomized trials. One group of patients will receive the experimental drug, while a second
“control” group will receive a standard treatment or placebo. Often these studies are “blinded” — neither the patients nor the researchers know who is getting the experimental drug. In this manner, the study can provide the pharmaceutical company and the FDA comparative information about the relative safety of the new drug, and its effectiveness. Only about one-third of experimental drugs successfully complete both phase I and phase II studies.

3 Phases to a Clinical Trial: Phase 1, Phase 2, Phase 3

Currently there are about 23 clinical research trials associated with dystonia — use of MyoBloc, deep brain stimulation, focal hand dystonia, EMG use in dystonia, diagnosis and history of neurological disorders. You can find more info about participating in any of these studies by visiting these websites:

Centerwatch.com
ClinicalTrials.gov (Dystonias Search)
CC.NIH.GOV
Dystonia Studies

Your participation is valuable in these studies. We do recommend that you learn about clinical trials before entering a research trial. You should ask yourself these questions before entering a trial:

• How long will the trial last?
• Where is the trial being conducted?
• What treatments will be used and how?
• What is the main purpose of the trial?
• How will patient safety be monitored?
• Are there any risks involved?
• What are the possible benefits?
• What are the alternative treatments besides the one being tested in the trial?
• Who is sponsoring the trial?

A Phase Three Study:

In a phase III study, a drug is tested in several hundred to several thousand patients. This large-scale testing provides the pharmaceutical company and the FDA with a more thorough understanding of the drug’s effectiveness, benefits, and the range of possible adverse reactions. Most phase III studies are
randomized and blinded trials.

Phase III studies typically last several years. Seventy to 90 percent of drugs that enter phase III studies successfully complete this phase of testing. Once a phase III study is successfully completed, a pharmaceutical company can request FDA approval for marketing the drug.

Post-Marketing — Late Phase Three/Phase Four Studies

In late phase III/phase IV studies, pharmaceutical companies have several objectives: (1) Studies often compare a drug with other drugs already in the market; (2) studies are often designed to monitor a drug’s long-term effectiveness and impact on a patient’s quality of life; and (3) many studies are designed to determine the cost-effectiveness of a drug therapy relative to other traditional and new therapies.