Generon’s F-652 Shows Positive Results in “An Open Label, Cohort Dose Escalation Study to Assess the Safety and Efficacy in Patients with Alcoholic Hepatitis”
Generon BioMed Holding Ltd announced the Phase IIa study results of “an open-label, cohort dose escalating study to assess the safety and efficacy of F-652 in patients with alcoholic hepatitis (AH)”. The results of this clinical study were presented at the American Association for the Study of Liver Diseases (AASLD) 2018 in San Francisco. The study was conducted by Dr. Vijay Shah, lead author and Chair and Professor, Division of Gastroenterology and Hepatology, and Internal Medicine at the Mayo Clinic. AH patients treated with F-652 demonstrated improvement in all parameters at day 42 and observed no serious adverse events (SAE).
The current phase IIa trial was a dose escalation study with doses (day 1 and 7) of 10, 30 and 45 μg/kg (n=6 each group) of F-652, in patients with moderate AH (MELD: 11-20) and severe AH (MELD: 21-28). Safety and tolerability of F-652 were assessed up to day 42 following administration of the first dose. Pharmacokinetics and pharmacodynamics were evaluated. Efficacy was assessed by Lille score, change in MELD score, bilirubin, and aminotransferases at day 42. Plasma extracellular vesicles (EVs) and multiple serum cytokines were quantified to assess potential inflammation.
In AH patients treated with F-652, there was a significant decrease in the MELD score, total bilirubin, ALT and AST at day 42 when compared to baseline. Subjects with severe AH had larger improvement in MELD scores at day 42. Lille score was ≤0.45 (defined as responders) in 15/18 patients (83%). The half-life of F-652 following the first dose was 85 ± 16 hrs. There were no SAEs related to the study drug. EV count decreased significantly at day 42 in parallel to the decreased MELD scores. Multiplex cytokine analysis showed downregulation of inflammatory markers: IL-8, MCP-1, CRP, IL-6; and upregulation of regeneration markers: angiopoietin2, FGF-β, PDGF-AA and PDGF-BB. In summary, F-652 is safe and is associated with high rate of Lille responsiveness and improvement in MELD score. F-652 administration correlated temporally with reductions in serum and plasma markers of inflammation in addition to increases in markers of regeneration.
Dr. Shah indicated that there is a need for novel therapies to treat AH. He is encouraged by the results and sees this as a step towards a larger trial in bringing this novel treatment to patients with AH. Dr. William Daley, Generon’s Chief Medical Officer, said, “the conclusion of the F-652 phase IIa trial is a significant accomplishment for Generon’s DiKine™ platform. The results from this study are yet another step in demonstrating Generon’s innovative capabilities in bringing novel therapies to patients.”
Dr. Xiaoqiang Yan, CEO/CSO of Generon, further commented, “We are very grateful for the scientific support from the Translational Research and Evolving Alcoholic Hepatitis Treatment consortium (TREAT), National Institute on Alcohol Abuse and Alcoholism (NIAAA) and National Institutes of Health (NIH) in developing a new and better treatment option for patients with acute AH. F-652 is a first-in-class biological drug with the potential to fulfill unmet medical needs for multiple indications including AH. This is a very important step in the long journey of developing F-652 from ‘bench-side to bed-side’, thus allowing us to better understand the biology of interleukin 22 in human diseases.”
About Alcoholic Hepatitis
Alcoholic Liver disease (ALD) is a major cause of alcohol-related morbidity and mortality of which AH is one stage along a continuum from fatty liver to alcoholic hepatitis (AH), cirrhosis, and hepatocellular carcinoma. The 30-day mortality for AH is 15 – 20% and is a significant global economic burden. In the US, there are approximately 5 million patients with ALD. Alcoholic hepatitis (AH) is a syndrome of progressive inflammatory liver injury associated with long-term heavy intake of alcohol. Patients who are severely affected would present with subacute onset of fever, hepatomegaly, leukocytosis, marked impairment of liver function (e.g., jaundice, coagulopathy), and manifestations of portal hypertension (e.g., ascites, hepatic encephalopathy, variceal hemorrhage).
Produced in Chinese Hamster Ovary (CHO) cells in serum-free cultures, F-652 is a recombinant fusion protein containing two human interleukin 22 (IL-22) and human IgG2-Fc. F-652 leverages Generon’s proprietary Dimeric Cytokine (DiKine™) technology platform to create an immunoglobulin-like dimeric structure, providing improved efficacy and a longer half-life. This product candidate is intended to treat inflammatory diseases with tissue injuries and immunologic disorders including graft vs host disease (GvHD), acute alcoholic hepatitis, and acute pancreatitis.
About Generon Corporation
Generon (Shanghai) Corporation (Generon) is a leading biotech company located in Shanghai, China focusing on development of innovative biological therapies for global patients. For more information on Generon, please visit http://www.generonbiomed.com.
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