Allergan, Inc. (NYSE: AGN) provided a further clarification on the U.S. Food and Drug Administration’s (FDA) conclusion to its “Early Communication” regarding a safety review of botulinum toxins in the United States.

On February 8, 2008, the FDA announced in an “Early Communication” that it was reviewing certain serious adverse events following the use of botulinum toxins. At the time, the FDA hosted a public teleconference, explaining that the review involved only a “relative handful of serious adverse events” and that the primary focus of the adverse events and the FDA’s review of them related to the therapeutic use of BOTOX to treat juvenile cerebral palsy and other large muscle, lower limb spasticities, particularly at higher doses in neurologically compromised patients.

Both before and after the Early Communication on February 8, 2008, Allergan provided adverse event reporting information and analyses from its safety database to the FDA. These days, the FDA took three actions:
1. The FDA approved the application of Ipsen and Medicis to sell its botulinum toxin in the United States for the treatment of cervical dystonia and glabellar lines, and in connection therewith required, among other things, a boxed warning regarding spread of toxin, safety language regarding the risks associated with the non-interchangeability of botulinum toxins and a risk evaluation and mitigation strategies (REMS) program to educate on spread and non-interchangeability;
2. The FDA informed Allergan that it believed Allergan should adopt the same language on spread and non-interchangeability and a similar REMS to that associated with DYSPORTTM;
3. The FDA announced the completion and results of its Early Communication and hosted a press conference to provide context regarding its results and requests to Allergan.

In its update to the early communication and press conference, the FDA explained the results of its analysis and its conclusion that there have been infrequent reports of serious adverse events associated with potential spread of product from the site of injection and that the risk is greatest in children treated for juvenile cerebral palsy but also in adults treated for spasticity or cervical dystonia who have underlying conditions that would predispose them to these symptoms. The proposed boxed warning provides similar context. Dr. Ellis Unger, M.D., Deputy Director (Acting) of the FDA’s Office of Drug Evaluation, answered questions and clarified the following in the press conference:
1. Dr. Unger explained that the reports of serious adverse events associated with possible distant spread are infrequent, appear to be largely dose dependent and, at labeled doses, BOTOX and BOTOX Cosmetic have a local effect;
2. Dr. Unger confirmed that there are no confirmed cases of serious adverse events associated with possible distant spread with the use of BOTOX Cosmetic at its labeled dose;
3. After the completion of its analysis, the FDA evaluation continues to support the recommendations made in February 2008;
4. Reports of serious adverse events, including hospitalization, have generally related to high doses in compromised populations with co-morbidities.

Finally, to provide additional context, it is important to understand that while bulk botulinum toxin is a potent biological agent, BOTOX is not bulk botulinum toxin. Instead, it is a finished medical product and a vial of BOTOX contains an extraordinarily minute amount (only four billionths of a gram) of botulinum toxin. BOTOX does not contain clostridium botulinum spores and does not cause botulism at labeled doses.

Allergan will work with the FDA to appropriately update the label for BOTOX and BOTOX Cosmetic in light of the FDA’s conclusions. In the interim, caution should be exercised if treating neurologically vulnerable patients with high doses of BOTOX. Allergan would also like to emphasize the following precautions:

* No other botulinum toxin is interchangeable with BOTOX or BOTOX Cosmetic and caution should be exercised when substituting another botulinum toxin for BOTOX or BOTOX Cosmetic.
* Patients should seek immediate medical attention if they develop the following symptoms: unexpected loss of strength or muscle weakness, hoarseness or trouble talking (dysphonia), trouble saying words clearly (dysarthria), loss of bladder control, trouble breathing, trouble swallowing, double vision, blurred vision and drooping eyelids.