A new formulation of botulinumtoxin A improved symptoms of cervical dystonia with effects seen over five to six months, according to findings presented at the AAN Annual Meeting.
In a multicenter, phase 3, double-blind, placebo-controlled trial, 301 people were randomized to either placebo, 125 units or 250 units of the drug known as daxibotulinumtoxinA, which has a proprietary peptide excipient.
At four to six weeks, the average change from baseline on the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) was a decline of 4.3 points for the placebo group, a decline of 12.7 points in the 125 units group, and a decline of 10.9 points in the 250 units group.
The Clinician Global Impression of Change and Patient Global Impression of Change scores improved as well, ranging from a little to very much. Most of the patients in the treatment groups were somewhat satisfied to very satisfied at week four—69.6 percent in the group taking 125 units and 62.3 percent of those taking 250 unit; at week six, 68.8 percent of those taking 125 units were very satisfied as were 66.2 percent taking 250 units.
The average duration of effect—the time it took to lose 80 percent of the peak treatment effect —was 24 weeks for those taking 125 units and 20.3 weeks for those taking 250 units.
The most commonly reported treatment-related adverse events were pain or erythema at the injection site, headache, muscle weakness, and musculoskeletal pain. Dysphagia was reported in 1.6 percent of those receiving 125 units and 3.9 percent on 250 units.
The longer effect than what is seen with other formulations and the lower incidence of dysphagia “suggests that this product might have some meaningful advantages," said Joseph Jankovic, MD, FAAN, director of the Parkinson's Disease Center and Movement Disorders Clinic at the Baylor College of Medicine. Patient feedback about existing treatments indicates these might be welcome advances, he said.
“Most of these patients are very happy and they benefit from it, but when you ask them what they dislike the most about the treatment they will say it's the relatively short duration of benefit," he said. “Usually after two and a half months or so, they start noticing more spasm, involuntary movements of the head and neck, and they obviously are looking forward to their next injection, which usually occurs every three months."
“With this treatment, they hopefully won't have to come in more than two or three times a year," he said.
Dysphagia is the most common side effect with existing treatments, occurring in 10- to 30-percent of patients, so the incidence with this new formulation is much lower. Little has been disclosed by the manufacturer about why the proprietary aspects of the drug might lead to longer benefit and a better side effect profile, but as the drug goes through the approval process over the next year or two, that picture might become clearer, Dr. Jankovic suggested.
Kristina Simonyan, MD, PhD, associate professor of otolaryngology-head and neck surgery at Harvard Medical School, where she studies dystonia, said that researchers are looking to improve upon existing therapies, and this new formulation appears to do that.
“It's very encouraging to see a well-formed, phase 3 clinical trial with placebo and different doses used in this population," Dr. Simonyan said. “It's not very often that we have a well-done clinical trial of medications used in clinical practice."
While noting this was not a head-to-head comparison with other formulations, she said she was struck by the duration of the drug's effects—five to six months, up from the typical three- to four-month effect seen with existing therapy.
Dr. Simonyan noted that the treatment does not addresses the disease pathophysiology, so it's a temporary management of symptoms. But, she added, the therapy improves how long the effect lasts, the side effects patients may have, and which groups of patients may benefit.
She added, “Some patients may benefit from five- to six-month re-injection," she said, rather than three to four months, which almost doubles the injection cycle. These reasons range from financing to discomfort and the psychological toll of repeated treatments, she said.
AAN Abstract: Jankovic J, Comella C, Hauser RA, et al. A phase 3 trial evaluating the efficacy, duration of effect, and safety of daxibotulinumtoxinA in the treatment of cervical dystonia.