CuraSen Therapeutics has commenced dosing of the first patient with CuraAX (CST-3056) in a Phase IIa proof-of-concept trial targeting neurogenic orthostatic hypotension (nOH), a serious condition affecting nearly 700,000 patients with Parkinson's disease and related alpha-synuclein disorders in the United States.
Addressing a Critical Unmet Medical Need
Neurogenic orthostatic hypotension is characterized by a sudden drop in blood pressure when a person moves from sitting to standing or from a supine position to sitting. This condition leads to debilitating dizziness, fainting, falls, hospitalizations, and cognitive impairment due to reduced blood flow to the brain. The condition affects patients with Parkinson's disease, multiple system atrophy (MSA), pure autonomic failure (PAF), and dementia with Lewy bodies (DLB). Diagnosis of nOH is associated with higher morbidity and mortality among these patients.
Novel Therapeutic Approach
CuraAX is administered as an oral tablet and functions as a selective partial α1A-adrenergic receptor agonist with central nervous system penetration. The drug is designed to stabilize blood pressure while maintaining cerebral blood flow, addressing both the cardiovascular and cognitive aspects of the condition.
"Dosing our first patient in this Phase 2a trial marks an important milestone for CuraAX and for patients living with nOH," said Kathleen Sereda Glaub, chief executive officer of CuraSen Therapeutics. "Our Phase 1 trial in healthy volunteers showed encouraging safety, tolerability and pharmacologic activity."
Competitive Advantages Over Current Treatments
According to Glaub, current treatments are limited by non-selective prodrug mechanisms, variable pharmacokinetics, burdensome dosing regimens, and significant side effects. "CuraAX has the potential to deliver stable, durable efficacy, improved safety and meaningful cognitive benefit. This represents an important best-in-class therapeutic opportunity for patients," she stated.
Trial Design and Endpoints
The Phase IIa dose-ranging study will evaluate safety, tolerability, and impact of CuraAX treatment on orthostatic signs and symptoms in patients with nOH and Parkinson's disease or pure autonomic failure. The study is expected to enroll up to 12 patients and will be conducted at sites in New Jersey and New York, as well as at the Vanderbilt Autonomic Dysfunction Center.
Participants will be blinded to study medication and will receive placebo and multiple dose levels of CST-3056 over five consecutive days. The primary endpoint is change in standing systolic blood pressure, while secondary endpoints include the Orthostatic Hypotension Symptom Assessment (OHSA), which serves as a registrational endpoint.
The principal investigator for the study is Italo Biaggioni, MD, professor of medicine and pharmacology, and an internationally recognized nOH expert.
Development Support and Pipeline
The IND-enabling and Phase I clinical trials for CuraAX received funding from the Alzheimer's Drug Discovery Foundation (ADDF). Beyond CuraAX, CuraSen's development pipeline includes CuraCN (CST-103/CST-107) and CuraXN (CST-2032/CST-107), both oral, CNS-penetrant β2-adrenergic receptor agonists combined with nadolol, a peripherally restricted beta-blocker.
These drug candidates are designed to restore adrenergic function that is lost early in neurodegenerative diseases and have demonstrated cognitive benefit in Phase 2 proof-of-concept studies in Parkinson's and Alzheimer's disease. Additional trials are planned for progressive supranuclear palsy and Alzheimer's disease.
