Botox Not Frowned At, But Gets A New Wrinkle

(RTTNews) - After reviewing the safety of botulinum toxin products, following reports of adverse reactions linked to their use, the FDA has mandated safety label changes, including a boxed warning, and a Risk Evaluation and Mitigation Strategy, or *REMS, for such products.

The products that have been required to carry the stringent warning label and *REMS include Botox and Botox Cosmetic, marketed by Allergan Inc. (AGN | Quote | Chart | News | PowerRating); Myobloc, marketed by privately-held Solstice Neurosciences and the newly-approved Reloxin, developed by Medicis Pharmaceutical Corp. (MRX | Quote | Chart | News | PowerRating) and France-based Ipsen SA.

*REMS is a strategy to manage a known or potential serious risk associated with a drug or biological product. It can include a Medication Guide, Patient Package Insert, a communication plan, elements to assure safe use, and an implementation system, and must include a timetable for assessment of the REMS.

Botulinum Toxins And Their Approved Uses

Botox is approved for treating conditions such as blepharospasm (spasm of the eyelids), cervical dystonia (severe neck muscle spasms), and severe primary axillary hyperhydrosis (excess sweating).

Botox Cosmetic is approved for temporary improvement in the appearance of moderate to severe facial frown lines. Botox and Botox Cosmetic are botulinum toxin type A.

Myobloc, which is botulinum toxin type B, is approved for the treatment of cervical dystonia in adults.

Dysport aka Reloxin approved as an anti-wrinkle treatment and also for cervical dystonia is a botulinum toxin type A.

However, the botulinum toxin products are being used for a number of off-label treatments of cerebral palsy, migraines, muscle spasms, enlarged prostate, overactive bladder and multiple sclerosis.

In early 2008, there were reports of adverse reactions, including respiratory failure and death, linked to botulinum toxin products, which were used under a wide range of doses and for treatment of a variety of conditions. The most severe adverse effects were found in children treated for spasticity in their limbs associated with cerebral palsy.

Treatment of spasticity is not an FDA-approved use of botulinum toxin products in children or adults. The dosages of the botulinum toxin products used to treat spastic disorders are much higher than those used to treat wrinkles.

The regulatory agency commenced a safety review of Allergan's Botox and Solstice's Myobloc last year. The FDA at the time said that the reported adverse reactions, which resemble botulism, have occurred when botulinum toxin spread beyond the site where it was injected. The FDA said that the adverse reactions were not related to any defect in the products.

The consumer advocacy group Public Citizen petitioned the FDA last year to slap the strictest warning possible on the botulinum toxin products and provide patients with a pamphlet explaining the risk.

Botulinum toxin is produced by the bacterium Clostridium botulinum, which in large amounts can cause botulism, very often associated with food poisoning. Symptoms of botulism include difficulty in swallowing or breathing, slurred speech, muscle weakness, or difficulty in holding up the head.

The most serious complication of botulism is paralysis because the botulinum toxin has the ability to block nerve signals transmitted from the brain to the muscle. This is the basis on which the Botox works.

However, Botox contains only minute amount of the toxin and is directly injected into specific muscles. The muscle injected with Botox will not be able to contract as the nerve signals get blocked, causing the wrinkles to relax and soften. The treatment effects of Botox can last for four to six months. Though intended to have a localized effect, sometimes the toxin spreads beyond the injection site, posing problems.

Reiterating its earlier finding, the FDA on Thursday said that 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. However, a higher dosage of Botox can cause adverse reactions.

Ellis Unger, acting deputy director of the FDA's Office of Drug Evaluation noted that while cosmetic uses of Botox require only smaller doses of the toxin, the dosage required may be higher for treating spasms, leading to adverse reactions.

During a teleconference, Unger said, "We don't want to discourage use of these drugs as patients taking them have significant disability and the drugs are effective to relieve important problems. But people just need to understand the risks that are involved so they can make informed, risk-benefit decisions."

According to the FDA officials, the adverse reactions must have been due to substituting one botulinum toxin product for another without corresponding dose adjustments.

Allergan has enjoyed a complete monopoly to date on the anti-wrinkle market in the U.S. through Botox. Developed in the 1970s by Alan Scot, Botox was then known as Oculinum. The FDA approved the drug in 1989 for treatment of crossed eyes and twitching eyelids. In 1991, Allergan acquired the right to Oculinum and changed its name to Botox.

Now that the FDA has approved Dysport, Botox may face some competition from the new drug. Dysport aka Reloxin was approved by the FDA as an anti-wrinkle treatment and also for cervical dystonia only a day before - on April 30, 2009.

Dysport has already been in use outside the U.S for over 15 years to smooth wrinkles and to treat neurological disorders. In 2008, Botox raked in global sales of $1.3 billion, while Dysport fetched sales of $189 million.

PurTox, an anti-wrinkle injection, which came into Johnson & Johnson's (JNJ | Quote | Chart | News | PowerRating) fold following its acquisition of Mentor Corp. is also waiting to enter the lucrative surgical anti-wrinkle market. The drug is yet to be approved by the FDA.

Meanwhile, Allergan is planning to expand the therapeutic uses of Botox. The company plans to seek approval to market Botox for chronic migraine headaches, later this year. However, the drug is already prescribed off-label for the same indication.

AGN closed Thursday's trading at $46.66 on a volume of 9.15 million shares.

MRX closed the day's trading at $16.07 on a volume of 3.77 million shares.

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