Hyperactive Wnt signaling is a key oncogenic signal in many types of cancer, and recently has been associated with resistance to cancer immunotherapeutics. OncoMed scientists have published a new manuscript in Science Advances on June 21 titled “WNT antagonists exhibit unique combinatorial anti-tumor activity with taxanes by potentiating mitotic cell death” . In this paper we describe a series of experiments in a large number of patient derived xenografts with two OncoMed developed compounds, vantictumab (anti-FZD) and ipafricept (FZD8-Fc). These two biologics are the most advanced Wnt pathway antagonists in clinical development. We discovered that these agents exhibit much better combination activity with taxanes than with other classes of chemotherapeutic agents, such as gemcitabine or platinum compounds. This is a robust phenomenon and occurs in diverse tumor types including breast, pancreatic, lung and ovarian cancers. Furthermore, we report that combination activity is enhanced by administration of the Wnt antagonist prior to taxane treatment. The combination of Wnt blockade and taxane treatment leads to a dramatic histological phenotype - mitotic cell death in tumor cells. Our hypothesis is that the unique combination activity relies on the action of taxane chemotherapy and inhibition of beta-catenin at the M phase of the cell cycle. This discovery has informed our clinical testing strategy and the mechanism of synergy has implications in understanding the role of Wnt/beta-catenin signaling in regulating the proliferation and differentiation of cancer cells.
Human growth hormone deficiency in children results in stunted growth and delayed muscle development and in adults in diminished lean body mass, poor bone density as well as a number of other physical and psychiatric symptoms. In addition to treating growth hormone deficiencies, somatropin is used to treat people with Turners syndrome and HARS, a syndrome associate with HIV infection, as well as certain other muscle wasting diseases due to its role in fat metabolism and muscle development. The market for somatropin products is currently estimated to be $ billion annually.
Generally, once a drug is released in the market by FDA, it has to be re-evaluated for its safety and efficacy once every six months for the first and second years. Afterward, re-evaluations are conducted yearly, and the result of the assessment should be reported to authorities such as FDA. Biosimilars are required to undergo pharmacovigilance (PVG) regulations as its reference product. Thus biosimilars approved by EMEA (European Medicines Agency) are required to submit a risk management plan (RMP) along with the marketing application and have to provide regular safety update reports after the product is in the market. The RMP includes the safety profile of the drug and proposes the prospective pharmacovigilance studies.