On April 24, 2017 Tiziana Life Sciences plc (AIM: TILS), a clinical stage biotechnology company developing targeted drugs for cancer and autoimmune diseases, reported the approval in Israel of a phase II clinical trial protocol for testing milciclib, a novel inhibitor of cell cycle dependent kinases (CDKs), in patients with refractory hepatocellular carcinoma ("HCC") (Press release, Tiziana Life Sciences, APR 24, 2017, http://www.tizianalifesciences.com/single-post/2017/04/24/Tiziana-Life-Sciences-Announces-Approval-of-a-Phase-II-Clinical-Trial-Protocol-for-Milciclib-in-Patients-with-Hepatocellular-Carcinoma [SID1234518675]). A similar clinical trial protocol has been submitted for approval in Italy, Turkey and Greece. The primary objective of these multi-centered, multi-country and dose-ranging phase IIa clinical studies is to evaluate the safety of milciclib in HCC patients who fail to respond or are intolerant to the existing standard of care treatment. First patient enrollment is expected next month and top line data from the trial is expected by Q3 2018. Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:
Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing
Schedule Your 30 min Free Demo!
In previous clinical studies, oral treatment with milciclib was found to be safe and well-tolerated in patients with refractory solid tumours, thymoma and thymic cancers. Data from animal studies has demonstrated that oral administration with milciclib effectively suppressed tumour growth in mouse models of HCC. Although the precise mode of action is not clearly understood, the preclinical studies conducted strongly suggest that milciclib acts primarily through downregulation of microRNA (miR) 221 and 222, which are known to be associated with hepatocarcinogenesis. Overexpression of miR-221 and miR-222 is also believed to be associated with development of resistance to sorafenib (Nexavar) in HCC patients
Gabriele Cerrone, Chairman of Tiziana commented: "HCC is a real unmet medical need due to its growing incidence and lack of effective therapy. It is the fifth most common cancer worldwide and the second most common cause of death from cancer worldwide. We strongly believe that milciclib has the potential to be developed either as a monotherapy or in combination with sorafenib for treatment of HCC."
Dr. Yaron Ilan, Director of the Department of Medicine at Hebrew University Hadassah Medical Center, Israel and Chief Medical Officer of Tiziana added: "The prognosis for liver cancer is very poor due to lack of effective therapy. We were very encouraged with recent pre-clinical findings and are now moving forward to conduct a phase II clinical trial in HCC patients with milciclib in patients that failed to respond to the standard of care therapy. We believe that milciclib holds promise as an effective anti-cancer treatment with a high safety profile."
About HCC
Hepatocellular carcinoma is the fifth most common cancer in men and the ninth in women. Additionally, it is the fifth most common cancer worldwide and the second most common cause of death from cancer worldwide[1]. The tumour is associated with chronic hepatitis B and chronic hepatitis C infections, as well as with nonalcoholic steatohepatitis. The prognosis for liver cancer is very poor due to lack of effective therapy.
About Milciclib
Milciclib (PHA-848125AC) is a small molecule inhibitor of several cyclin dependent kinases (CDKs) such as CDK1, CDK4, CDK5 and CDK7. CDKs are serine threonine kinases that play crucial roles in progression of the cell cycle from G1 to S phase. Overexpression of CDKs and other downstream signaling pathways that regulate cell cycles have been frequently found to be associated with development of resistance towards chemotherapies. Oral treatment with milciclib was found to be effective in reducing tumour growth in animal models of HCC, possibly through downregulation of miR-221 and miR-222. In a phase I study, oral treatment with milciclib was found to be well-tolerated and the drug showed promising clinical responses in patients with advanced solid malignancies such as in thymic carcinoma, pancreatic carcinoma and colon cancer.