Cytokinetics recently presented patient baseline characteristics from its VITALITY-ALS clinical trial investigating Tirasemtiv for the treatment of amyotrophic lateral sclerosis (ALS). Data collected from an international physician survey on the use of noninvasive ventilation (NIV) in the treatment of ALS also was presented. Both presentations were made at the 27th International Symposium on ALS/MND in Dublin, Ireland.
The Phase 3 VITALITY-ALS (NCT02496767) trial is evaluating Tirasemtiv for its safety, tolerability and effectiveness, and was designed to confirm and extend findings on measures of respiratory function and muscle strength from prior studies. The trial screened 866 patients, enrolled 744 and randomized 566 to receive a placebo or Tirasemtiv at 125 mg twice a day for up to four weeks, and gradually increase to their maximum tolerated dose of 250 mg twice a day. Secondary endpoints include time to events such as the first use of assisted ventilation or respiratory insufficiency, and the change from baseline ALS functional rating scale-revised (ALSFRS-R) — a validated rating instrument for monitoring the progression of disability in patients with ALS.
According to the data presented at the meeting in Dublin, patients participating in the trial average 57.6 years of age, 65% are male, 7.7 months from their ALS diagnosis, 20.6 months from their first disease symptom, and had an average slow vital capacity (SVC) — a measure of respiratory function — of 90.7%.
The most commonly observed adverse events in patients taking part in the trial include dizziness, fatigue and nausea. The company also reported that almost 24% of patients withdrew from the study during the two-week open-label phase, due to the adverse treatment reactions.
“We’re pleased to provide the first look at the patient population from VITALITY-ALS and note the consistency with previously conducted large-scale ALS trials,” Jeremy M. Shefner, MD, PhD, lead investigator of VITALITY-ALS, said in a press release. “We look forward to sharing full results from VITALITY-ALS in late 2017 and remain hopeful that treatment with Tirasemtiv may slow the decline of SVC and other measures of muscle strength including measures of respiratory function,” said Shefner, who also is professor and chair of neurology at Barrow Neurological Institute, and professor and executive chair of neurology at the University of Arizona, Phoenix.
An international physician survey evaluated the use of noninvasive ventilation (NIV) (positive pressure ventilation delivered through a noninvasive interface), a technique that improves survival in patients with ALS. The data showed there exist similarities in best practices for initiating NIV between North America and Europe, however there are differences in the time to initiation. U.S. specialists ranked upright and supine forced vital capacity (FVC, the amount of air which can be forcibly exhaled from the lungs after taking the deepest breath possible), as well as symptoms of shortness of breath, as the main factors for initiating NIV, while European specialists prioritize symptoms of shortness of breath, sleep-related symptoms, and supine slow vital capacity (SVC).
The results also showed that in the U.S., 70% of specialists reported that insurance regulations and national healthcare coverage impact time to NIV initiation, compared to 47.5% of EU specialists. Differences regarding NIV initiation also differed when considering the FVC/SVC value, with the majority of U.S. specialists defending an upright FVC/SVC of more than 50% vital capacity, while European specialists more often initiating NIV at a higher upright FVC/SVC of more than 70% or 80%.
“Although we found geographic differences in how and when noninvasive ventilation is used, vital capacity remains one of the most important measures influencing the decision,” Terry Heiman-Patterson, MD, director of the Center for Neurodegenerative Disorders, and professor of the Department of Neurology at the Lewis Katz School of Medicine at Temple University, said in the release. “These results help us understand what additional research is needed to optimize NIV use in all patients, and may help inform the design of future clinical trials in ALS,” he said.
Tirasemtiv is a novel skeletal muscle activator that triggers the muscle troponin complex, increasing its sensitivity to calcium. In preclinical studies and early clinical trials involving more than 1,000 people worldwide, Tirasemtiv demonstrated improvements in skeletal muscle force in response to neuronal input and delays in disease onset, as well as a decrease in muscle fatigue.