STOCKHOLM. Umecrine Cognition AB, a Karolinska Development (Nasdaq Stockholm: KDEV) portfolio company, today announced enrollment of the first patient in the final part of a Phase 2a study designed to assess the safety, pharmacokinetics and potential benefit of GR3027, a novel GABAA receptor modulating steroid antagonists (GAMSA), under development for treatment of Hepatic Encephalopathy (HE).
The ongoing Phase 1b/2a study (protocol UCAB-CT-02 parts A-D) is designed to evaluate the safety and pharmacokinetics of multiple ascending doses of GR3027 in healthy adults and patients with cirrhosis, as well as its potential effect on cognitive function in patients with cirrhosis and covert HE.
In part B of the trial, 8 adult male patients with Child-Pugh B cirrhosis were randomized (6:2) to receive a single dose of 10mg of GR3027 or placebo. GR3027 was well tolerated; there were no SAEs and adverse events were mild and mainly judged as unrelated to study treatment. Dosing was recently completed in the first cohort of the ongoing and blinded part C of this protocol, which is designed to assess the safety and PK of multiple ascending doses in adults with cirrhosis. In this first dose cohort of 8 patients randomized 6:2 to received 10 mg BID of GR3027 or placebo, safety continued to be excellent with no SAEs or dose-limiting toxicity and generally mild AEs. GR3027 has also exhibited excellent PK characteristics so far in cirrhotic patients, just as it has in healthy adults.
Part D of protocol UCAB-CT-02, for which the company today announced dosing of the first patient, is designed to further assess safety during 3-weeks of dosing as well as the potential benefit of GR3027 on cognitive function among cirrhotic patients with evidence of impaired brain function at the time of enrollment.
Liver disease and its complications account for a growing and substantial disease burden worldwide. Hepatic encephalopathy (HE) is a syndrome of episodically impaired brain function that frequently complicates decompensated liver cirrhosis and is hugely burdensome to patients and their families as well as to society. Symptoms of HE range from impaired cognition (covert HE) to clinically evident impairment (overt HE) manifested by a spectrum of abnormalities ranging from confusion to depressed consciousness and coma. There are today no treatments available that directly target the brain abnormalities believed to responsible for HE. GR3027 has been shown to improve or normalize cognitive function and learning in two animal models of hepatic encephalopathy [1] and, in humans, a single oral dose of GR3027 has been shown to dose dependently mitigate the brain-inhibitory effects of the intravenously administered neurosteroid allopregnanolone [2].
“Umecrine Cognition is, to the best of our knowledge, the only company with a drug candidate in clinical development designed to reduce the risk of the serious CNS related symptoms associated with liver failure,” said Magnus Doverskog, CEO of Umecrine Cognition. “We are very encouraged by the favorable safety, tolerability and pharmacokinetic profile of GR3027 seen so far and excited to start exploring GR3027 in patients with cirrhosis and hepatic encephalopathy, a population badly in need of new treatments for their often severely disabling and dehumanizing neurological symptoms.”
For further information, please contact:
Magnus Doverskog, CEO, Umecrine Cognition AB
Phone: +46 (0)73 039 20 52, e-mail: [email protected]
TO THE EDITORS
About Umecrine Cognition AB
Umecrine Cognition, a Karolinska Development (Nasdaq Stockholm: KDEV) portfolio company, is developing a potential therapy that represents a new target class relevant for several major CNS-related disorders. The primary focus is to develop a treatment for life-threatening overt Hepatic Encephalopathy and long-term treatment in minimal Hepatic Encephalopathy in patients with liver disease, a growing area with high unmet medical need. The current lack of therapeutics that directly addresses the neurocognitive signs and symptoms of Hepatic Encephalopathy makes a novel treatment likely to become a major contribution for the treatment of this disorder. For more information, please visit www.umecrinecognition.com.
References
- Johansson et al., Am J Physiol Gastrointest Liver Physiol 2015; 309: G400–G409.
- Johansson et al., Psychopharmacology 2018; 235:1533-1543