Trial will use digital biomarkers to assess short-term ALS progression
Verge Genomics testing VRG50635 therapy in patients in Phase 1b study
Verge Genomics has identified multiple digital clinical biomarkers that can be used to assess short-term disease progression in the pre-treatment run-in period of a Phase 1b trial testing VRG50635, its treatment candidate for amyotrophic lateral sclerosis (ALS), in patients.
These digital biomarkers measure changes in key functions, such as mobility, breathing, sleeping, and speech, that are affected in people with ALS. They also can be used to objectively assess disease progression occurring after eight weeks of monitoring before treatment start, according to the company.
Data were presented at the 77th Annual Meeting of the American Academy of Neurology, held April 5-9, in San Diego and virtually.
“We are thrilled to be the first company to evaluate multiple digital clinical biomarker endpoints in an ALS therapeutic trial to gauge short-term disease progression across key functional domains,” Diego Cadavid, MD, chief medical officer of Verge Genomics, said in a company press release. “Given the high unmet need and complexity of ALS, it is critical to leverage innovative technologies early in clinical development to assess potential treatment benefits.”
Ongoing Phase 1b trial enrolled patients with sporadic, familial ALS
ALS is caused by the progressive dysfunction and death of motor neurons, the nerve cells that control muscle movement. Several factors may contribute to neuron loss, including the accumulation of misfolded proteins inside neurons, all ultimately resulting in cell damage.
An oral therapy, VRG50635 is designed to increase nerve cell ability to clear these toxic protein clumps by blocking a protein called PIKfyve and increasing the number of lysosomes inside cells. Lysosomes are cellular compartments that normally break down molecules that are defective or no longer needed. They’re essential to prevent the accumulation of toxic proteins, and are usually dysfunctional in ALS.
VRG50635 is therefore expected to slow ALS progression and potentially extend patient survival.
In preclinical studies, the therapy extended the survival of motor neurons. It also was found to be safe in healthy volunteers participating in a Phase 1 clinical trial (ISRCTN14792372).
The ongoing proof-of-concept Phase 1b study (NCT06215755) is assessing the safety and tolerability of VRG50635 in 54 people with sporadic and familial types of ALS. Patient enrollment was completed last year at sites in Europe and Canada, and efficacy and safety results are expected later this year.
Patients taking part in the Phase 1b trial will receive multiple ascending doses of VRG50635, followed by long-term treatment with the highest tolerated dose.
The trial’s main goal is to determine the treatment’s safety, with secondary goals of evaluating changes in disease progression, markers of nerve damage, and the treatment’s pharmacological properties.
Verge ID’d digital biomarkers to assess speech, sleep, mobility changes
In the initial run-in part of the study, repeated measures of biomarkers will be used to establish mean baseline levels before treatment is started. In the second part, patients will receive progressively increasing doses of VRG50635 — 400, 600, and 800 mg — for eight weeks. In the third and final part of the trial, patients will receive the maximum tolerated dose determined in part 2 for up to 40 weeks, or about nine months.
The company has now announced that it’s identified several digital clinical biomarkers that can be used to assess changes in mobility, breathing, sleep, and speech. These biomarkers are also expected to objectively evaluate short-term ALS progression.
“Verge’s ALS trial was designed from the outset to continuously and objectively measure changes in various key ALS patient functions in real-world settings while minimizing patient burden.
The digital technology used to objectively measure disease-relevant changes include touchless wireless sensors, developed by Emerald Innovations to monitor walking speed, bed movements, and breathing changes, as well as sleep efficiency and time awake after sleep onset.
“Verge’s ALS trial was designed from the outset to continuously and objectively measure changes in various key ALS patient functions in real-world settings while minimizing patient burden,” said Dina Katabi, PhD, president and cofounder of Emerald Innovations.
Accelerometers (ActiGraph) were also used to track the total number of steps taken and the time spent in moderate to vigorous activity using wearable devices. An online artificial intelligence-based speech platform (Modality.AI) was also used to assess sustained production of speech sounds and time to read a passage.
David “DSO” Suendermann-Oeft, PhD, the CEO of Modality.AI, called the study’s design “innovative,” noting it “allowed us to assess ALS-related changes in participants’ speech before their first dose” of the therapy.
“We observed significant changes in articulation and respiration, both critical for communication and quality of life,” with VRG50635, Suendermann-Oeft said.
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