Myobloc (rimabotulinumtoxinB) (2 indications)

Scroll down for information on each indication:

• the treatment of cervical dystonia; approved December 2000
• the treatment of chronic sialorrhea in adults; approved August 2019

General Information

Myobloc (rimabotulinumtoxinB) is an acetylcholine release inhibitor.

Myobloc is specifically indicated for the following:

• the treatment of cervical dystonia to reduce the severity of abnormal head position and neck pain associated with cervical dystonia in adults
• the treatment of chronic sialorrhea in adults

Mechanism of Action

Myobloc (rimabotulinumtoxinB) is an acetylcholine release inhibitor. Myobloc blocks cholinergic transmission at the neuromuscular and salivary neuroglandular junction by inhibiting the release of acetylcholine from peripheral cholinergic nerved terminals. This inhibition occurs according to the following sequence: neurotoxin binding to cholinergic nerve terminals, internalization of the neurotoxin into the nerve terminal, translocation of the light-chain part of the molecule into the cytosol of the nerve terminal, and enzymatic cleavage of synaptic Vesicle Associated Membrane Protein (VAMP, also known as synaptobrevin), a presynaptic target protein essential for the release of acetylcholine. In both muscles and glands, impulse transmission is re-established by the formation of new nerve endings.

Side Effects

Adverse effects associated with the use of Myobloc for cervical dystonia may include, but are not limited to, the following:

• dry mouth
• dysphagia
• injection site pain
• headache

Adverse effects associated with the use of Myobloc for chronic sialorrhea may include, but are not limited to, the following:

• dry mouth
• dysphagia

The Myobloc drug label comes with the following Black Box Warning: The effects of Myobloc and all botulinum toxin products may spread from the area of injection to produce symptoms consistent with botulinum toxin effects. These symptoms have been reported hours to weeks after injection. Swallowing and breathing difficulties can be life threatening and there have been reports of death. The risk of symptoms is probably greatest in children treated for spasticity but symptoms can also occur in adults, particularly in those patients who have an underlying condition that would predispose them to these symptoms.

Indication 1 - cervical dystonia

approved December 2000

Dosing/Administration

The recommended initial dosage of Myobloc for cervical dystonia patients with a prior history of tolerating botulinum toxin injections is 2,500 Units to 5,000 Units divided among affected muscles. Patients without a prior history of tolerating botulinum toxin injections should receive a lower initial dosage. Subsequent dosing should be determined by the patient’s individual response. Myobloc should be administered by physicians familiar with and experienced in the assessment and management of patients with cervical dystonia. The duration of effect in patients responding to Myobloc treatment for cervical dystonia has been observed in studies to be between 12 and 16 weeks at doses of 5,000 Units or 10,000 Units.

Clinical Trial Results

The FDA approval of Myobloc for cervical dystonia was based on two phase III studies involving a total of 186 adult subjects. The primary efficacy outcome of the trials was the Toronto Western Spasmodic Torticollis Rating Scale, which examines the severity of abnormal head position, the severity and duration of pain, and the disabiling effects placed on the person's activities. Subjects were randomized to receive placebo, 5000 Units, or 10000 Units in single treatment sessions and were evaluated for 16 weeks following injection.

There were no statistically significant differences between the 5000 U and the 10000 U doses. Most subjects who reported improvements after four weeks had returned to their baseline status by the end of the 16 weeks. Subjects in the two treatment groups did experience decreases in pain, though many also reported increases in symptoms regardless of receiving treatment or placebo.

Indication 2 - chronic sialorrhea in adults

approved August 2019

Dosing/Administration

Myobloc is supplied as an injection for intra-salivary gland administration. The recommended dose for chronic sialorrhea is 1,500 Units to 3,500 Units, divided among the parotid and submandibular glands, per the directions below. Patient response to treatment should be considered when determining subsequent Myobloc dosage. The typical duration of effect of each treatment is up to 3 months; however, the effect may vary in individual patients. The frequency of Myobloc repeat treatments should be determined by clinical response but should generally be no more frequent than every 12 weeks.

Dosing by Gland for Chronic Sialorrhea in Adults:

• Gland: Parotid Recommended dose: 500 Units to 1,500 Units per gland

• Gland: Submandibular Recommended dose: 250 Units per gland

Clinical Trial Results

The FDA approval of Myobloc for chronic sialorrhea was based on a multicenter, randomized, double-blind, placebo-controlled study of a single treatment (with 13-week follow-up), followed by an open-label treatment period. A total of 187 adult patients with chronic, troublesome sialorrhea for at least 3 months were randomized to receive treatment with Myobloc 2,500 Units, 3,500 Units, or placebo. Patients had chronic sialorrhea associated with Parkinson’s disease (n=122), amyotrophic lateral sclerosis(ALS) (n=12), stroke (n=13), and other causes (n=40). Patients with a history of aspiration or severe dysphagia in the last 6 months and ALS patients with a forced vital capacity of less than 20% of predicted were excluded from the study. A single treatment was administered, consisting of bilateral injections of Myobloc into the parotid (1,000 Units or 1,500 Units per gland) and submandibular (250 Units per gland) salivary glands or volume matched placebo. A total of 114 patients received 4 consecutive treatments with 3,500 Units of Myobloc every 11 to 15 weeks. The co-primary efficacy endpoints for Study 1 were the change from baseline in Unstimulated Salivary Flow Rate (USFR) and the Clinical Global Impression of Change (CGI-C) assessed 4 weeks after treatment in the double-blind part of the study. The CGI-C is a seven-point Likert scale with scores ranging from “1=very much improved” to “7=very much worse”. The change from baseline (i.e., decrease) in USFR at Week 4 was significantly greater for patients treated with Myobloc than in patients on placebo. Similarly, CGI-C scores at Week 4 were significantly lower (i.e., better) in patients treated with Myobloc than in patients on placebo. Chronic sialorrhea was ‘much improved’ or ‘very much improved’, according to CGI-C scores at Week 4 post injection, in patients treated with Myobloc 2,500 Units (60%) and Myobloc 3,500 Units (53%) than in patients on placebo (12%).