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Allergan Receives FDA Approval for First-of-Its-Kind, Fully in vitro, Cell-Based Assay for BOTOX® and BOTOX® Cosmetic (onabotulinumtoxinA)

--Represents R&D Breakthrough in Commitment to Animal-Free Stability and Potency Testing for BOTOX® and BOTOX® Cosmetic--

IRVINE, Calif.--(BUSINESS WIRE)-- Allergan, Inc. (NYSE:AGN) today announced the United States Food and Drug Administration (FDA) has approved a fully in vitro, cell-based assay for use in the stability and potency testing of BOTOX® (onabotulinumtoxinA) and BOTOX® Cosmetic. The newly approved assay will be implemented immediately for release of product for sale in the United States. Allergan estimates that use of the new assay will reduce the use of animal-based assay testing for BOTOX® and BOTOX® Cosmetic by up to 95 percent or more over the next three years, as other regulatory agencies around the world approve this new assay. The new assay is the first to be developed and approved for any botulinum neurotoxin currently available worldwide, and is specifically applicable to Allergan's botulinum toxin type A product.

"We are proud to have achieved this major scientific milestone in the development of a safe and effective alternative test capable of eliminating the need for an animal-based assay for BOTOX®," said Scott Whitcup, M.D., Allergan's Executive Vice President, Research and Development and Chief Scientific Officer. "Following the FDA approval, we will work hard to secure approval of the new assay to replace the current animal testing requirements for the release and stability testing of BOTOX® and BOTOX® Cosmetic in countries in which we market and distribute the product."

The FDA approval follows more than a decade of Allergan research and development and an approximately $65 million investment directed toward minimizing to the greatest degree possible the need for animal-based assays in the manufacture of BOTOX® and BOTOX® Cosmetic. The mouse LD50 potency assay is required by the FDA, the Medicines and Healthcare products Regulatory Agency (MHRA) in Europe and regulatory agencies around the world for testing final product for release to assure its safety and efficacy. Limitations associated with the current mouse LD50 assay, which has been the standard for potency and stability testing of BOTOX® and BOTOX® Cosmetic and other botulinum neurotoxin type A products, include the necessary involvement of animals due to the current structure of the assay, the complexity of the procedures involved, lack of specificity, as well as variability between assays and laboratories.

"The new cell-based potency assay we have developed for BOTOX® and BOTOX® Cosmetic has many advantages over current methods including the potential for greater precision and consistency in stability and potency testing, making this a significant breakthrough in both the science and manufacturing of neurotoxins," said Timothy Terrell, DVM, Ph.D, DACVP, Allergan's Senior Vice President, Drug Safety Evaluation.

Currently all pharmaceutical manufacturers are required by the FDA and by other worldwide health regulatory agencies to protect patients and consumers by assuring product safety and efficacy through animal testing and other methods. BOTOX® is a unique and complex biological product with 21 different approved medical uses, and is derived from natural sources — in this case from the bacterium C. botulinum. When manufacturing biological products, testing is particularly critical to ensuring the consistent safety and efficacy of each batch of product. BOTOX® and BOTOX® Cosmetic are the same product, manufactured in exactly the same way, and therefore the potency and stability of each batch must be determined before release, regardless of whether the batch is intended for medical or aesthetic use. BOTOX® is Allergan's only product that has required use of an animal-based assay for stability and potency testing, as mandated by global regulatory authorities to ensure safe product use in humans.

About the BOTOX® Cell-Based Potency Assay (CBPA)

Over the years a number of attempts have been made to find strategies to replace the animal-based LD50 assay for testing of botulinum neurotoxins but have fallen short for a variety of reasons. Botulinum neurotoxin is one of the most potent naturally occurring substances and has a complex multi-stage mechanism of action. Purified botulinum neurotoxin type A is the active ingredient in BOTOX® and blocks the release of neurotransmitters from nerves, resulting in a localized and temporary reduction in the overacting muscle or gland. The amount of neurotoxin in BOTOX® is extremely small; in fact, less than one gram per year is required to supply the entire world.

A suitable replacement potency assay to the LD50 assay must therefore be sensitive enough to measure the complex mode of action of extremely small amount of the neurotoxin used in BOTOX® in the cellular level. Established performance criteria against which the new cell-based potency assay needed to be validated included the ability to assess all primary modes of action of the neurotoxin. In addition, the new assay format had to be suitable for use in an intensely quality-controlled environment and at the high capacity needed to support commercial production.

"This significant achievement was made possible by Allergan scientists' long-standing leadership and deep expertise in neurotoxin research and development, and by our corporate commitment to the '3R' principles of refinement, reduction and eventual replacement of laboratory animals in the final manufacturing stages of BOTOX®," said Dr. Terrell.

The new cell-based potency assay for BOTOX® and BOTOX® Cosmetic is specific to Allergan's formulation of botulinum neurotoxin type A. Allergan is discussing how to license the technology to other parties that share its commitment to implementing non-animal alternatives to animal-based assays in the manufacture of their medical products.

About BOTOX® (onabotulinumtoxinA)

BOTOX® is a prescription-only medical product that contains tiny amounts of highly purified botulinum toxin protein refined from the bacterium, Clostridium botulinum. BOTOX® has a unique, protected molecular structure that stabilizes the core toxin in BOTOX® from degradation. When injected at FDA-approved and labeled doses into a specific muscle or gland, BOTOX® neurotoxin is expected to diffuse locally and produce a safe and effective result by producing a localized and temporary reduction in the overacting muscle or gland, usually lasting up to approximately three months depending on the individual patient.

BOTOX® was first approved by the FDA 21 years ago for the treatment of strabismus and blepharospasm, two eye muscle disorders, making it the first botulinum toxin type A product approved in the world. Since its first approval, BOTOX® has been recognized by regulatory authorities worldwide as an effective treatment for 21 different indications in approximately 80 countries, benefiting millions of patients worldwide. In the United States, BOTOX® neurotoxin is also approved to treat the abnormal head position and neck pain that happens with cervical dystonia (CD) in adults, symptoms of severe underarm sweating (severe primary axillary hyperhidrosis) when medicines used on the skin (topical) do not work well enough, as well as for the treatment of increased muscle stiffness in elbow, wrist, and finger muscles in adult patients with upper limb spasticity.

In addition to its therapeutic uses, the same formulation of BOTOX® with dosing specific to moderate to severe glabellar lines was approved by the FDA in 2002 under the trade name BOTOX® Cosmetic (onabotulinumtoxinA). BOTOX® Cosmetic is indicated for the temporary improvement in the appearance of moderate to severe glabellar lines (frown lines between the eyebrows) associated with corrugator and/or procerus muscle activity in adult patients up to 65 years of age. Most recently, in 2010, BOTOX® was approved by the FDA for the prophylactic treatment of headaches in adults with Chronic Migraine, a distinct and severe neurological disorder characterized by patients who have a history of migraine and suffer from headaches on 15 or more days per month with headaches lasting four hours a day or longer. This latest indication marks the sixth therapeutic indication for the product in the United States since 1989.

In addition to 21 years of clinical experience, the safety and efficacy of BOTOX® have been well-established in approximately 50 randomized, placebo-controlled clinical trials and in approximately 11,000 patients treated with BOTOX® and BOTOX® Cosmetic in Allergan's clinical trials.1 Worldwide, approximately 26 million vials of BOTOX® and BOTOX® Cosmetic have been distributed and approximately 29 million treatment sessions have been performed over the past 20 years (1989-2009).2 With approximately 2,300 articles on BOTOX® and BOTOX® Cosmetic in scientific and medical journals,3 BOTOX® neurotoxin is one of the most widely researched medicines in the world.

BOTOX® (onabotulinumtoxinA) & BOTOX® Cosmetic Important Information

Indications
BOTOX® is a prescription medicine that is injected into muscles and used:

  • to prevent headaches in adults with chronic migraine who have 15 or more days each month with headache lasting 4 or more hours each day in people 18 years or older
  • to treat increased muscle stiffness in elbow, wrist, and finger muscles in people 18 years and older with upper limb spasticity
  • to treat the abnormal head position and neck pain that happens with cervical dystonia (CD) in people 16 years and older
  • to treat certain types of eye muscle problems (strabismus) or abnormal spasm of the eyelids (blepharospasm) in people 12 years and older

BOTOX® is also injected into the skin to treat the symptoms of severe underarm sweating (severe primary axillary hyperhidrosis) when medicines used on the skin (topical) do not work well enough in people 18 years and older.

BOTOX® Cosmetic is a prescription medicine that is injected into muscles and used to improve the look of moderate to severe frown lines between the eyebrows (glabellar lines) in people 18 to 65 years of age for a short period of time (temporary).

It is not known whether BOTOX® and BOTOX® Cosmetic are safe or effective to prevent headaches in patients with migraine who have 14 or fewer headache days each month (episodic migraine).

It is not known whether BOTOX® and BOTOX® Cosmetic are safe or effective to treat increased stiffness in upper-limb muscles other than those in the elbow, wrist, and fingers, or to treat increased stiffness in lower-limb muscles. BOTOX® has not been shown to help people perform task-specific functions with their upper limbs or increase movement in joints that are permanently fixed in position by stiff muscles. Treatment with BOTOX® is not meant to replace your existing physical therapy or other rehabilitation that your doctor may have prescribed.

It is not known whether BOTOX® and BOTOX® Cosmetic are safe or effective for severe sweating anywhere other than your armpits.

IMPORTANT SAFETY INFORMATION
BOTOX® and BOTOX® Cosmetic may cause serious side effects that can be life threatening. Call your doctor or get medical help right away if you have any of these problems any time (hours to weeks) after injection of BOTOX® or BOTOX® Cosmetic:

  • Problems swallowing, speaking, or breathing, due to weakening of associated muscles, can be severe and result in loss of life. You are at the highest risk if these problems are pre-existing before injection. Swallowing problems may last for several months
  • Spread of toxin effects. The effect of botulinum toxin may affect areas away from the injection site and cause serious symptoms including: loss of strength and all-over muscle weakness, double vision, blurred vision and drooping eyelids, hoarseness or change or loss of voice (dysphonia), trouble saying words clearly (dysarthria), loss of bladder control, trouble breathing, trouble swallowing. If this happens, do not drive a car, operate machinery, or do other dangerous activities

There has not been a confirmed serious case of spread of toxin effect away from the injection site when BOTOX® has been used at the recommended dose to treat chronic migraine, severe underarm sweating, blepharospasm, or strabismus, or when BOTOX® Cosmetic has been used at the recommended dose to treat frown lines.

Do not take BOTOX® or BOTOX® Cosmetic if you: are allergic to any of the ingredients in BOTOX® or BOTOX® Cosmetic (see Medication Guide for ingredients); had an allergic reaction to any other botulinum toxin product such as Myobloc® (rimabotulinumtoxinB), Dysport® (abobotulinumtoxinA), or Xeomin® (incobotulinumtoxinA); have a skin infection at the planned injection site.

The dose of BOTOX® and BOTOX® Cosmetic is not the same as, or comparable to, another botulinum toxin product.

Serious and/or immediate allergic reactions have been reported. These include itching, rash, red itchy welts, wheezing, asthma symptoms, or dizziness or feeling faint. Tell your doctor or get medical help right away if you experience any such symptoms; further injection of BOTOX® or BOTOX® Cosmetic should be discontinued.

Tell your doctor about all your muscle or nerve conditions such as amyotrophic lateral sclerosis (ALS or Lou Gehrig's disease), myasthenia gravis, or Lambert-Eaton syndrome, as you may be at increased risk of serious side effects including severe dysphagia (difficulty swallowing) and respiratory compromise (difficulty breathing) from typical doses of BOTOX® or BOTOX® Cosmetic.

Tell your doctor if you have any breathing-related problems. Your doctor will want to monitor you for any breathing problems during your treatment with BOTOX® for upper limb spasticity.

Cornea problems have been reported. Cornea (surface of the eye) problems have been reported in some people receiving BOTOX® for their blepharospasm, especially in people with certain nerve disorders. BOTOX® may cause the eyelids to blink less, which could lead to the surface of the eye being exposed to air more than is usual. Tell your doctor if you experience any problems with your eyes while receiving BOTOX®. Your doctor may treat your eyes with drops, ointments, contact lenses, or with an eye patch.

Bleeding behind the eye has been reported. Bleeding behind the eyeball has been reported in some people receiving BOTOX® for their strabismus. Tell your doctor if you notice any new visual problems while receiving BOTOX®.

Bronchitis and upper respiratory tract infections (common colds) have been reported. Bronchitis was reported more frequently in people receiving BOTOX® for their upper limb spasticity. Upper respiratory infections (common colds) were also reported more frequently in people with prior breathing-related problems.

Human albumin and spread of viral diseases. BOTOX® and BOTOX® Cosmetic contain albumin, a protein component of human blood. The potential risk of spreading viral diseases (eg, Creutzfeldt-Jakob disease [CJD]) via human serum albumin is extremely rare. No cases of viral diseases or CJD have ever been reported in association with human serum albumin.

Tell your doctor about all your medical conditions, including if you have: plans to have surgery; had surgery on your face; weakness of forehead muscles, such as trouble raising your eyebrows; drooping eyelids; any other abnormal facial change; are pregnant or plan to become pregnant (it is not known if BOTOX® or BOTOX® Cosmetic can harm your unborn baby); are breastfeeding or plan to breastfeed (it is not known if BOTOX® or BOTOX® Cosmetic passes into breast milk).

Tell your doctor about all the medicines you take, including prescription and nonprescription medicines, vitamins, and herbal products. Using BOTOX® or BOTOX® Cosmetic with certain other medicines may cause serious side effects. Do not start any new medicines until you have told your doctor that you have received BOTOX® or BOTOX® Cosmetic in the past.

Especially tell your doctor if you: have received any other botulinum toxin product in the last 4 months; have received injections of botulinum toxin such as Myobloc®, Dysport®, or Xeomin® in the past (be sure your doctor knows exactly which product you received); have recently received an antibiotic by injection; take muscle relaxants; take an allergy or cold medicine; take a sleep medicine.

Other side effects of BOTOX® and BOTOX® Cosmetic include: dry mouth, discomfort or pain at the injection site, tiredness, headache, neck pain, and eye problems: double vision, blurred vision, decreased eyesight, drooping eyelids, swelling of your eyelids, and dry eyes.

For more information refer to the Medication Guide or talk with your doctor.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088.

For BOTOX® and BOTOX® Cosmetic full Product Information including Boxed Warning and Medication Guide click here.

Forward-Looking Statement

This press release contains "forward-looking statements", including but not limited to the statements by Drs. Whitcup and Terrell, statements regarding the anticipated reduction in use of animal-based assay testing and other statements regarding the Cell-Based Potency Assay and the safety, efficacy, and product availability BOTOX®. These statements are based on current expectations of future events. If underlying assumptions prove inaccurate or unknown risks or uncertainties materialize, actual results could vary materially from Allergan's expectations and projections. Risks and uncertainties include, among other things, general industry and pharmaceutical market conditions; technological advances and patents attained by competitors; challenges inherent in the research and development and regulatory processes; challenges related to new product marketing, such as the unpredictability of market acceptance for new pharmaceutical products and/or the acceptance of new indications for such products; inconsistency of treatment results among patients; potential difficulties in manufacturing a new product; general economic conditions; and governmental laws and regulations affecting domestic and foreign operations. Additional information concerning these and other risk factors can be found in press releases issued by Allergan, as well as Allergan's public periodic filings with the U.S. Securities and Exchange Commission, including the discussion under the heading "Risk Factors" in Allergan's 2010 Annual Report on Form 10-K and subsequent Quarterly Reports on Form 10-Q. Copies of Allergan's press releases and additional information about Allergan is available on the World Wide Web at www.allergan.com.

About Allergan, Inc.

Allergan is a multi-specialty health care company established more than 60 years ago with a commitment to uncover the best of science and develop and deliver innovative and meaningful treatments to help people reach their life's potential. Today, we have more than 9,000 highly dedicated and talented employees, global marketing and sales capabilities with a presence in more than 100 countries, a rich and ever-evolving portfolio of pharmaceuticals, biologics, medical devices and over-the-counter consumer products, and state-of-the-art resources in R&D, manufacturing and safety surveillance that help millions of patients see more clearly, move more freely and express themselves more fully. From our beginnings as an eye care company to our focus today on several medical specialties, including ophthalmology, neurosciences, medical aesthetics, medical dermatology, breast aesthetics, obesity intervention and urologics, Allergan is proud to celebrate 60 years of medical advances and proud to support the patients and physicians who rely on our products and the employees and communities in which we live and work.

1 Allergan data on file; Medical Affairs

2 Allergan data on file; Global Regulatory Affairs

3 Allergan data on file; Global Literature & Information Services

Allergan Contacts
Caroline Van Hove 714-246-5134 (media)
Crystal Muilenburg 714-246-5842 (media)
Jim Hindman 714-246-4636 (investors)
Joann Bradley 714-246-4766 (investors)
David Nakasone 714-246-6376 (investors)

Source: Allergan, Inc.

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