Allergan, Inc has received a complete response letter from the US Food and Drug Administration (FDA) regarding the company's Supplemental Biologics License Application (sBLA) for Botox (Botulinum Toxin Type A) to treat upper limb spasticity in post-stroke adults. Allergan submitted its sBLA for this indication in the third quarter of 2008.

The FDA has not requested additional pre-approval clinical studies. However, the FDA has identified items that must be completed before the sBLA can be considered for approval.

Firstly, FDA wants Allergen to complete Risk Evaluation and Mitigation Strategy (REMS) and safety update - on April 29, 2009, the FDA approved Dysport (abobotulinumtoxinA) for the treatment of cervical dystonia in adults and the temporary improvement in the appearance of moderate to severe glabellar lines in adults younger than 65 years of age and imposed a REMS for that product. Concurrently, the FDA requested that Allergan adopt a substantially similar REMS for Botox. Allergan has submitted its proposed REMS for the FDA's review. The FDA indicated that it had not yet reviewed Allergan's submission and that an approved REMS will be necessary prior to approving Botox to treat upper limb spasticity. Also, the FDA requested that in its reply to the complete response letter, Allergan provide a product safety update from clinical and non-clinical studies across indications.

Second is source data documentation - while the FDA's complete response letter acknowledges that the sBLA supports the efficacy and safety of Botox for the treatment of upper limb spasticity, the FDA has requested that Allergan independently verify underlying patient source documentation at study sites relating to one of the pivotal clinical studies conducted in 1999 and upon completion of the verification, provide an updated analysis. In the sBLA, Allergan submitted data from 16 studies including an integrated analysis of seven double-blind, placebo-controlled trials.

Allergan estimates that the re-verification can be completed and the analysis submitted to the FDA in approximately 60 to 90 days.

Next is product labelling - in its complete response letter, the FDA proposed revisions to Allergan's proposed labelling, including enhanced safety information and other clarifications. Among other revisions, the FDA proposed a revised spasticity indication. In its sBLA, Allergan proposed the use of Botox for the treatment of upper limb spasticity associated with stroke. In its complete response letter, the FDA noted the focal nature of Botox treatments and the similarities of spasticity across conditions and thus proposed revised labelling that would broaden the indication of use to upper limb spasticity regardless of underlying cause. Also, noting the number of paediatric patients such as those with juvenile cerebral palsy who suffer from upper limb spasticity, the FDA requested that Allergan conduct a post-approval study for Botox to treat upper limb spasticity in paediatric patients two to 17 years of age. This request is consistent with Allergan's proposal in connection with the submission of its proposed REMS and Allergan hopes to discuss with the FDA a protocol that, if successful, would support an approval for the treatment of children suffering from spasticity.

Allergan will diligently respond to the FDA's proposed label revisions and will develop a paediatric plan to further study Botox in children.

"A significant unmet medical need for those suffering from upper limb spasticity exists in the United States. It is estimated that nearly 500,000 Americans each year develop stroke-related spasticity, the majority of which includes upper limb spasticity. And yet about half of those patients receive no treatment for their spasticity," said Scott Whitcup, executive vice president, Research & Development, chief scientific officer, Allergan. "We have already submitted our REMS for Botox as we anticipated this requirement as a condition to an approved spasticity indication. We will work expeditiously to provide the FDA with all other information requested in the complete response letter to support a rapid final review of our application for Botox as a treatment for upper limb spasticity."

Botox is a prescription-only medical product that contains tiny amounts of highly purified botulinum toxin protein refined from the bacterium, Clostridium botulinum.

Founded in 1950, Allergan, with headquarters in Irvine, California, is a multi-specialty health care company that discovers, develops and commercializes innovative pharmaceuticals, biologics and medical devices that enable people to live life to its greatest potential - to see more clearly, move more freely, express themselves more fully.