FDA approves BOTOX for treatment of increased muscle stiffness in adults with upper limb spasticity

Mar 9 2010

Allergan, Inc. (NYSE: AGN) today announced that the United States Food and Drug Administration (FDA) has approved BOTOX^® (onabotulinumtoxinA) for the treatment of increased muscle stiffness in the elbow, wrist and fingers in adults with upper limb spasticity.

“In the clinical studies, we saw improvement in muscle tone in patients injected with BOTOX®, which was maintained for up to three months with no further injection.”

Spasticity is a debilitating condition impacting approximately 1 million Americans, many of whom suffer from spasticity in the upper limbs following a stroke. Upper limb spasticity may also occur following a spinal cord or traumatic brain injury or in patients affected by multiple sclerosis or adults with a history of cerebral palsy.

Although not a life-threatening condition, upper limb spasticity can be severely debilitating and painful, producing disfiguring muscle contractions that can result in stiff, tight muscles in the elbow, wrist and fingers, or a clenched fist. This stiffness hinders a patient’s ability to perform simple tasks, such as dressing or washing the hand, and often leaves the patient dependent on a caregiver to help with simple activities.

“Upper limb spasticity can manifest weeks, months or even years after the original injury, possibly after a patient has stopped seeing a neurologist, physiatrist or their rehabilitation specialist, which is why it is severely undertreated and there’s a low awareness of the condition,” said Mitchell F. Brin, MD, Allergan’s Senior Vice President Global Development, Chief Scientific Officer, BOTOX^®. “The approval of BOTOX^® marks another important evolution in medical care, as we look to raise greater recognition and understanding of upper limb spasticity among patients affected by the condition, and refer them to a neurologist or physiatrist to explore their various treatment options.”

In patients diagnosed with upper limb spasticity, BOTOX^® is injected by a trained specialist directly into the affected muscles, blocking overactive nerve impulses that trigger these disabling contractions to reduce the severity of increased muscle tone in the elbow, wrist and fingers. In clinical studies, the efficacy of BOTOX^® persisted up to three months on average. BOTOX^® is the first and only neurotoxin approved by the FDA for the treatment of upper limb spasticity.

Clinical Studies Evaluating BOTOX^® For the Treatment of Upper Limb Spasticity

Allergan has conducted multiple studies evaluating the use of BOTOX^® to treat upper limb spasticity, including three double-blind, placebo-controlled studies, two of which were published in The New England Journal of Medicine, and Archives of Physical and Medical Rehabilitation.

The first double-blind, placebo-controlled trial compared the safety and efficacy of BOTOX^® treatment (200-240 units (U)) with placebo over a 12-week period in 126 patients who had suffered a stroke at least 6 months prior and experienced increased wrist and finger flexor tone (scores of at least 3 for wrist flexor tone and at least 2 for finger flexor tone based on the Ashworth Scale). The Ashworth Scale is a globally accepted measure of muscle tone, which rates passive movement from 1 (normal muscle tone) to 4 (extreme increase in muscle tone).

The study found that BOTOX^® neurotoxin produced a statistically significant reduction in both wrist flexor and finger flexor muscle tone seen at the week six primary endpoint (P < .05 versus placebo). Further, evaluation by the Physician’s Global Assessment score, an investigator’s measure of a patient’s response to treatment, correlated with the Ashworth scores, showing a statistically significant difference favoring BOTOX^® versus placebo at the primary endpoint (week 4).

The second study compared three doses of BOTOX^® (360 U, 180 U, 90 U) with placebo over 24 weeks in 91 patients at least 6 weeks post-stroke with increased elbow flexor and wrist flexor tone (a score of at least 2 for elbow flexor tone and at least 3 for wrist flexor tone based on an expanded Ashworth Scale). In this study, the 360 U group achieved statistically significant reduction versus placebo in wrist flexor tone at the week 6 primary endpoint.

Similar results were observed in a clinical study that compared the same dosing regimens of BOTOX^® (360 U, 180 U, 90 U) with placebo over 12 weeks in 88 patients at least 6 weeks post-stroke with increased elbow tone and wrist and/or finger tone (scores of at least 2 for elbow flexor tone and at least 3 for wrist and/or finger flexor tone based on the Ashworth Scale). This study showed BOTOX^® decreased muscle tone and achieved statistically significant decreases in wrist flexor tone, finger flexor tone and elbow flexor tone in the 360 U group at week 4.

“For patients who suffer from upper limb spasticity, simple activities can be so challenging they must rely on a caregiver to pry open their hand and stretch back their fingers so they can wash their hands or get dressed,” said Allison Brashear, M.D., Professor and Chair, Department of Neurology at Wake Forest University Baptist Medical Center in Winston-Salem, NC. “In the clinical studies, we saw improvement in muscle tone in patients injected with BOTOX^®, which was maintained for up to three months with no further injection.”

In the double-blind, placebo-controlled studies of BOTOX^® for the treatment of upper limb spasticity, the most common adverse events occurred in less than 7 percent of patients and included pain in extremity, fatigue, muscle weakness, nausea and bronchitis .