Our clinical drug candidate, golexanolone, is currently in Phase 2 clinical development for the treatment of patients with primary biliary cholangitis (PBC) exhibiting fatigue with cognitive impairment – central fatigue. The company is also evaluating other disorders that affect patients’ ability to think and reason – processes that include memory, attention, language, and problem-solving – and neurodegenerative disorders such as Parkinson’s Disease (PD).
PRIMARY BILIARY CHOLANGITIS
Approximately 190,000 patients are diagnosed with PBC in the world’s seven largest pharmaceutical markets (7MM; US, UK, France, Germany, Italy, Spain and Japan). In the US alone, there are an estimated 100,000 patients. The initial target population consists of PBC patients experiencing debilitating central fatigue, which is approximately one-third of all patients. In total, this translates to 63,000 patients in the 7MM.
In 2021, the global PBC treatment market was valued at USD 584 million, and it is projected to reach USD 3 billion by 2027. Currently approved drugs, ursodeoxycholic acid and OCALIVA® and, more recently, Iqirvo® and Livdelzi®, slow the PBC disease progression, but do not relieve patients from fatigue or cognitive impairment. As a benchmark, Iqirvo® and Livdelzi® list prices correspond to approximately USD 150,000 per patient per year, in the US.
The global pooled prevalence of PBC continues to increase, but with only about 18 people in 100,000, PBC still meets the FDA’s and the EMA’s criteria as a rare disease. Thus, qualifying golexanolone for orphan designation, potentially providing extended market exclusivity and accelerated development and approval processes. Golexanone received FDA orphan drug designation in 2023.
OTHER POTENTIAL INDICATIONS
Diseases featuring overlapping mechanisms of neural inhibition, cognitive dysfunction and debilitating fatigue – where a GABAA-modulating agent such as golexanolone might be explored – include Parkinson’s disease, schizophrenia, multiple sclerosis and amyotrophic lateral sclerosis, offering further opportunities for indication expansion.
PARKINSON’S DISEASE
Parkinson’s disease is the world’s second-most-common neurodegenerative disease and constitutes a chronically progressive degenerative disorder characterized by a strong variety of symptoms – both traditionally highlighted motor symptoms, such as tremors, as well as non-motor symptoms affecting patients’ cognitive function and mental health. As motor and nonmotor symptoms accelerate in severity, they become a notable burden on a patient’s quality of life.
Current pharmaceutical management in Parkinson’s disease is primarily focused on augmenting dopamine signaling (dopaminergic) for improved motor function but there are no current medications that alter the course of the disease. These dilemmas point to a need for further drug discovery beyond the current dopaminergic strategy. Treatment of non-motor symptoms has become an important unmet need in management of Parkinson’s disease, and a new therapeutic drug that effectively improves cognitive impairments, excessive daytime sleepiness, and fatigue in would have significant health economic upsides and provide important quality-of-life benefits. Umecrine Cognition’s research aims to offer benefits in this area as well as potentially for the course of the disease.
Approximately 2.6 million people in the 7MM had a diagnosed form of Parkinson’s disease (PD) in 2023, a number that is forecasted to reach 3.1 million by 2033. In the United States alone, nearly 1 million people live with PD. Of all PD patients, roughly 35-50% suffer from fatigue, while mild cognitive impairment (PD-MCI) occurs in 30-40%.
The global PD-treatment market was valued at USD 4.3 billion in 2021 and is projected to reach USD 12 billion by 2030. Current standard of care therapies – levodopa/carbidopa, dopamine agonists, MAO-B inhibitors and deep-brain stimulation – improve motor symptoms but have little impact on fatigue or cognitive impairment; for cognition, rivastigmine is the only drug with level-1 evidence and offers modest benefit. Recently-approved Vyalev™ (foslevodopa/foscarbidopa) illustrates the pricing landscape at USD 119,000 per patient per year in the US.