Shanghai, China, November 8, 2011: Hutchison MediPharma Limited (HMP) today announces the initiation of the first-in-human Phase I clinical trial of Epitinib (HMPL-813). This is the third oncology compound from the internal discovery programs of HMP to enter into clinical study in China. Epitinib is a novel, second generation, orally active small molecule inhibitor targeting the epidermal growth factor receptor (EGFR), designed for optimal tissue distribution to achieve broader anti-tumor activity. The first patient was dosed on October 31, 2011.
The primary objectives of the Phase I study of Epitinib are to evaluate its safety and tolerability in patients and to determine its maximum tolerated dose. The study will also evaluate its preliminary efficacy against various tumors, including tumors carrying activating EGFR mutations that have metastasized to the brain from other cancers such as non-small cell lung cancer.
In preclinical studies, Epitinib demonstrated excellent brain penetration and good efficacy in orthotopic brain tumor models and reached drug concentrations in the brain tissue that are expected to result in robust efficacy when given orally at doses well below toxic levels. Epitinib was also found to have good pharmacokinetic properties and a favorable safety profile. If the preclinical findings are confirmed in clinical studies, Epitinib could become a breakthrough therapy for patients with primary brain tumors or tumors metastasized to brain carrying activating EGFR mutations.
About the epidermal growth factor receptor (EGFR) in cancer
The epidermal growth factor receptor (EGFR) is a protein that is a cell-surface receptor for epidermal growth factors (EGFs). Activation of EGFR can lead to a series of downstream signaling activities that mediate tumor cell proliferation, migration, invasion, and the suppression of cell death. Treatment strategies for certain cancers relate to inhibiting EGFRs with small molecule tyrosine kinase inhibitors, such as Epitinib (HMPL-813).
First generation small molecule EGFR inhibitors such as gefitinib (Iressa™) and erlotinib (Tarceva™) are used for the treatment of non-small cell lung cancer, particularly in patients with EGFR-related mutations. Worldwide sales of Tarceva™ alone reached approximately US$1.3 billion in 2010. EGFR mutations occur in about 10-30% of non-small cell lung cancer patients and are a hallmark for treatment success. In addition to non-small cell lung cancer, EGFR mutations are also found in 30-40% of glioblastoma patients. The currently available EGFR inhibitors lack satisfactory clinical efficacy against primary brain tumors or tumors metastasized to the brain from other organs such as the lung, largely attributable to insufficient drug penetration into the brain.
About lung cancer and brain metastasis
The estimated incidence of lung cancer worldwide was over 1.6 million in 2008, with over 520,000 cases in China. Lung cancer is the most common cancer both worldwide and in China.
Brain metastases occur in 8-10% of cancer patients and are a significant cause of cancer-related morbidity and mortality worldwide. The most common origins of brain metastasis include primary cancers of the lung, breast, skin and the gastrointestinal tract. Among these, primary tumors of the lung are the most common cause of brain metastasis, as it has been estimated that 50% of patients with lung cancer will ultimately develop brain metastasis. Studies suggest a potential role for EGFR inhibitors in the treatment of brain metastasis, although gefitinib and erlotinib have thus far demonstrated only modest clinical efficacy.