Analyses of Cytokinetics’ Clinical Data Provide Insights on ALS Care, Trial Design
Exploratory analysis of data collected in the FORTITUDE-ALS and VITALITY-ALS trials sponsored by Cytokinetics provide new insights to enhance the design of future clinical trials in amyotrophic lateral sclerosis (ALS).
Slow vital capacity (SVC) is often used to measure the respiratory function in patients with ALS. However, its use in clinical trials requires patients to go to a clinic, which can be a challenge.
In the study “Correlation between slow vital capacity measured in the home and in the clinic for patients with amyotrophic lateral sclerosis” (page 266), researchers explored the possibility of using a portable spirometer to measure SVC at home.
The team analyzed data collected during the ongoing Phase 2 trial FORTITUDE-ALS (NCT03160898) that is evaluating the activity of Cytokinetics’ investigational candidate reldesemtiv (formerly known as CK-2127107) in ALS.
Approximately 347 ALS patients were trained to use portable spirometers and measure their SVC at home. Then within a week, the patients would have their SVC measured at a clinic. The SVC measured at home was consistently higher than that at the clinic, with a mean difference of 0.153 liters that translates to “differences in percent predicted SVC of more than 10 percentage points,” researchers stated.
This finding suggests that measuring SVC at home to decrease the frequency of clinic visits during a trial “may not be advisable,” they stated.
In another finding, results from the completed Phase 3 VITALITY-ALS (NCT02496767) have failed to demonstrate the potential of Cytokinetics’ investigational therapy tirasemtiv to improve muscle strength and respiratory function in ALS patients. However, new analyses of VITALITY-ALS data have provided insights on how to optimize the development of ALS therapies.
Researchers found that patients diagnosed with ALS in the past 6.1 months or less experienced positive changes in SVC upon 24 weeks of treatment with tirasemtiv compared to placebo. In contrast, no difference was found in SVC values between tirasemtiv and placebo-treated patients who had been diagnosed more than 6.1 months ago.
Patients in the early stages of the disease also showed some improvement in overall motor function and relief of symptoms, favoring tirasemtiv treatment.
“Selecting for early-onset patients is consistent with other ALS development programs. These results may help to further inform clinical trial design in future studies in ALS,” they wrote.
Additional analyses also evaluated the impact of non-invasive ventilation for ALS patients during the VITALITY-ALS trial.
Among 565 ALS patients who participated in the trial, 195 (34.5%) were prescribed non-invasive ventilation and 153 (78.5%) used it at least two hours per day. The three most common reasons assisted ventilation was prescribed were decline in vital capacity, respiratory symptoms, and sleep-related symptoms.
Although the patients were allowed to use ventilation assistance after randomization in VITALITY-ALS, researchers found that only two out of three patients whose SVC fell below 50% were prescribed non-invasive ventilation.
“Differences in non-invasive ventilation prescribing among centers and countries could influence survival outcomes in ALS patients,” they stated. “These results may inform future ALS trial design and encourage best practices in non-invasive ventilation use at ALS centers.”
These findings were reported in the studies “Impact of time since diagnosis on response to tirasemtiv, a fast skeletal muscle troponin activator, in patients with amyotrophic lateral sclerosis: a subgroup analysis of VITALITY-ALS” (page 278) and “Non-invasive ventilation use in patients enrolled in VITALITY-ALS” (page 266).
Other results regarding the needs of the ALS community were also presented at the conference.