Peretinoin (Kowa/Chugai Pharmaceutical) is a synthetic acyclic retinoid inhibitor of transforming growth factor alpha (TGF-alpha) and platelet-derived growth factor receptor (PDGFR). TGF-alpha induces epithelial development, and is closely involved in hepatocarcinogenesis. Inhibition of TGF-alpha prevents tumor growth by inducing apoptosis in cancer cells. It is expressed highly in the liver tissues of patients with hepatitis C virus. Peretinoin-inhibition of TGF-alpha expression suppressed cell proliferation and growth of liver tumors in rats. PDGFR is important for angiogenesis, and overexpression of its ligand, PDGF, is linked to various malignancies. Peretinoin was shown to repress PDGFR expression in a mouse cell model, which resulted in decreased tumor development.
Kowa/Chugai Pharmaceutical are positioning peretinoin (K-333) as an adjuvant therapy in Japan for hepatitis C virus (HCV)-positive early-stage hepatocellular cancer (HCC) patients who have undergone curative surgery. The predefined primary analysis of Phase II/III data failed to show that peretinoin had a significant effect in HCC. A significant dose-response relationship was demonstrated only after re-evaluation of the data with a set of contrasts. Based on uncertainty regarding peretinoin’s efficacy, Datamonitor Healthcare believes that it is unlikely the drug will gain approval for the treatment of HCC.
TABLE OF CONTENTS
4 PRODUCT PROFILES
4 peretinoin : Hepatocellular cancer
LIST OF FIGURES
6 Figure 1: Phase II/III results for adjuvant peretinoin in hepatocellular cancer
7 Figure 2: Peretinoin’s SWOT analysis for hepatocellular cancer
9 Figure 3: Datamonitor Healthcare’s drug assessment summary for peretinoin in hepatocellular
9 Figure 4: Datamonitor Healthcare drug assessment summary for peretinoin in hepatocellular
LIST OF TABLES
4 Table 1: Peretinoin – drug profile
5 Table 2: Clinical development of peretinoin in hepatocellular cancer
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