Interim Data From Phase 2 Trial of AC220 Monotherapy in Patients With Relapsed or Refractory Acute Myeloid Leukemia With FLT3-ITD Activating Mutations

LONDON, June 13, 2011, 2011 /PRNewswire/ --Ambit Biosciences Corporation and Astellas Pharma Inc. announced today results from a planned interim analysis in an ongoing Phase 2 study evaluating AC220, a potent and selective FLT3 inhibitor. The study is evaluating AC220 as an oral, once-a-day, monotherapy treatment in acute myeloid leukemia (AML) in 240 patients with FLT3-ITD activating mutations who have relapsed or are refractory to other treatments, including chemotherapy and hematopoietic stem cell transplant (HSCT). The data from this analysis was presented in an oral session at the 16th Annual Congress of the European Hematology Association (EHA) in London.

"AML patients who relapse or fail to respond to front-line chemotherapy have poor prognoses, and patients that harbor mutations in the FLT3 kinase are at an increased risk of disease relapse," said Mark Levis, MD, PhD, Associate Professor, Oncology and Medicine, Division of Hematologic Malignancies, Johns Hopkins, Baltimore, Maryland, and an investigator in the Phase 2 study. "Once these patients progress, the options available to them are limited, poorly tolerated by the majority of patients, and often ineffective. We presently lack an acceptable standard of care for AML patients with FLT3-ITD activating mutations once they fail front-line treatment."

This interim analysis reported on clinical response and safety in a subset of patients from the ongoing Phase 2 open-label, single-arm, multi-center study conducted in the United States and Europe. Safety data was reported on 62 patients and clinical response data was reported on a group of 53 patients who met the efficacy evaluable (EE) criteria. Patients included in the analysis were either greater than or equal to 60 years old and relapsed or refractory to first-line chemotherapy (Cohort 1, N=25), or greater than or equal to 18 years old and relapsed or refractory to second-line chemotherapy or HSCT (Cohort 2, N=37).

The co-primary end points of the study are composite complete remission rate (CRc) and complete remission rate in the first 84 days. CRc is defined as the sum of complete remission (CR), complete remission with incomplete platelet recovery (CRp), and complete remission with incomplete hematologic recovery (CRi). In the efficacy evaluable population, there was a composite complete response (CRc) rate of 45% for all patients, and 41% and 48% in Cohort 1 and Cohort 2, respectively, with the majority of CRc cases represented by CRi, with no CRs observed, in the first 84 days. Notably, a CRc rate of 62% was achieved in patients who were refractory to the prior line of treatment (N=16). Key secondary end points in the study include duration of remission, rates of partial response, and overall survival. The median duration of response for patients achieving a CRc was 12.1 weeks and 10.6 weeks in all patients and Cohort 2, respectively, with patients censored at the time of transplant. Cohort 1 has yet to achieve a median duration of response. In addition to the observed CRc rate, an additional 25% of efficacy evaluable patients achieved a partial response (PR). The median survival of efficacy evaluable patients was 24.7 weeks and 24.1 weeks for all patients and Cohort 1, respectively. Cohort 2 has yet to achieve a median survival, with 22 out of 31 patients alive at time of analysis. More than one-third of the patients in the safety population for Cohort 2 who had previously failed both induction chemotherapy and salvage therapy transitioned to HSCT.

No treatment-related deaths have been reported at the time of the analysis. The most common treatment-related adverse events included nausea, vomiting, fatigue, and febrile neutropenia. Several cases of asymptomatic QTc prolongation were reported early in the study, but most resolved following a dose adjustment, and no Grade 4 cases have been reported. Management of other adverse events is also being explored with dose modifications in the ongoing study.

About AC220

AC220 is being developed in collaboration between Ambit Biosciences and Astellas Pharma Inc., and is a novel, potent, highly selective, orally bioavailable FMS-like tyrosine kinase-3 (FLT3) inhibitor. AC220 is currently under evaluation in a Phase 2 clinical trial as mono-therapy treatment for adult and elderly patients with relapsed/refractory AML that have an internal tandem duplication (ITD) mutation in the FLT3 gene. AML is one of the most common types of blood cancers in adults, with ITD mutations in the FLT3 gene occurring in 25-30 percent of AML patients. FLT3 ITD mutations confer poor prognosis, with early relapse and lower survival following treatment with existing therapies, including chemotherapy and hematopoietic stem cell transplant.

About AML

Acute myeloid leukemia is a form of blood cancer. According to the American Cancer Society, approximately 13,000 adults were newly diagnosed with AML in 2009 in the United States with approximately 9,000 expected to die of the disease in that year. AML is generally a disease of older people and is uncommon before the age of 40. The average age of a patient with AML is 67 and median survival for these patients is less than six months. The five-year survival rate for all AML patients is less than 15 percent. According to a report from Decision Resources, the U.S. AML market is expected to more than double by 2015.

About the Ambit/Astellas Collaboration

In December 2009, Ambit and Astellas entered into a global strategic partnership agreement to jointly research, develop and commercialize FLT3 kinase inhibitors in multiple indications, including the lead investigational compound, AC220. The companies are presently evaluating AC220 in a Phase 2 clinical trial in relapsed and refractory AML patients that have the internal tandem duplication (ITD) mutation in the FLT3 gene. The companies are also collaborating on a comprehensive development program to explore the utility of AC220 in other AML patient subpopulations. Additionally, the companies are collaborating on a research and development program for additional FLT3 inhibitors for a variety of oncology and non-oncology indications. The companies share equal responsibility and expenses for the development of products in the US and Europe, while Astellas has sole responsibility in the rest of the world. Astellas will be responsible for implementation of commercialization activities worldwide. Ambit received a $40 million up-front payment upon entering into the collaboration agreement, and is eligible to receive up to $350 million in development milestone payments, undisclosed sales milestones, and tiered, double-digit royalties on global revenues. Ambit also has an option to co-promote products in the U.S. where Astellas and Ambit share equally all profits and losses generated from U.S. sales.

About Ambit Biosciences

Ambit Biosciences is a privately-held biopharmaceutical company engaged in the discovery and development of small molecule kinase inhibitors for the treatment of cancer, inflammatory disease, and other indications. Ambit's lead compound, AC220, is a novel, potent, highly selective, orally bioavailable FMS-like tyrosine kinase-3 (FLT3) inhibitor, and is currently under clinical investigation in patients with relapsed or refractory AML. Ambit is developing AC220 in collaboration with Astellas Pharma Inc. as part of a worldwide agreement to jointly develop and commercialize FLT3 kinase inhibitors in oncology and non-oncology indications. In addition to AC220, Ambit's clinical pipeline includes AC480, an oral pan-HER inhibitor, and AC430, an oral JAK2 inhibitor. Ambit also has a pipeline of preclinical candidates which includes CEP-32496, a BRAF inhibitor licensed to Cephalon.

About Astellas

Astellas Pharma Inc., located in Tokyo, Japan, is a pharmaceutical company dedicated to improving the health of people around the world through provision of innovative and reliable pharmaceuticals. Astellas has approximately 16,000 employees worldwide. The organization is committed to becoming a global category leader in Urology, Immunology & Infectious Diseases, Oncology, Neuroscience, and DM complications & Metabolic Diseases. For more information on Astellas Pharma Inc., please visit our website at http://www.astellas.com/en.

Source: Astellas Pharma Inc.

Contacts: Ambit Biosciences: Alan Fuhrman, Chief Financial Officer, +1-858-334-2133; Doug Sherk/Jenifer Kirtland, EVC Group, +1-415-896-6820; Media: Janine McCargo, EVC Group, +1-646-528-4034; Astellas Pharma Inc: Corporate Communications, +81-3-3244-3201

Posted: June 2011

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