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Our Initiatives to Create Innovation

Case 2 Steady Progress in Oncology

With several late-stage development projects progressing,
we are taking up the challenge of making breakthroughs in cancer treatment.

Bernie Zeiher, M.D.
President, Development

Portrait of Bernie Zeiher, M.D

Targeting Scientific Advances while Accelerating Development Using Varied Approaches

We have made progress in oncology on several fronts recently. In late-stage development, we have begun several new Phase 3 clinical trials with enzalutamide, gilteritinib and ASP8273. In early-stage development, the data obtained in metastatic bladder cancer with the two Agensys, Inc. antibody-drug-conjugates are also promising.
Oncology is a complex therapeutic area given the number of tumor types, differences in pathogenesis and changing treatment paradigm. What makes it even more complex is the pace of change recently due to the advancement of new breakthrough therapies.
Personalized or precision medicine approaches have made a significant impact on the development of treatments in oncology. Utilizing a more targeted approach, we anticipate an improved benefit-risk profile by administrating the right drug to the right patient. This approach is taken with enzalutamide in triple-negative breast cancer, gilteritinib and ASP8273. Immunooncology is another area of interest, where we are engaged in partnership with Potenza Therapeutics, Inc.
It is vital to take advantage of accelerated development pathways. Gilteritinib is a good example where we have been granted SAKIGAKE designation in Japan.
Our challenge at Astellas is to improve cancer treatment globally by turning innovation into value for patients. We continue to follow the evolution of science so that we can remain on the forefront of the dramatic changes in the management of cancer patients.

Clinical Development Program #1
Enzalutamide (Prostate/breast cancer, etc.)

Prostate cancer is the second most prevalent type of cancer in men, with 1.1 million new cases diagnosed in 2012 globally. It has the fifth highest mortality rate among cancers in men*.
Enzalutamide, which is indicated in treatment of metastatic castration-resistant prostate cancer, both post-chemo and chemo-naÏve, has offered a new treatment option since its launch as XTANDI. It is currently in Phase 3 trials for three earlier stages of prostate cancer shown in the figure below. This comprehensive program, conducted with our partner Medivation, Inc., will help to characterize the optimal use of enzalutamide in this disease. Enzalutamide is also being evaluated in breast cancer, including a Phase 3 program in triple-negative breast cancer and two Phase 2 studies in different breast cancer subtypes.

*World Health Organization, GLOBOCAN 2012: Estimated Cancer Incidence, Mortality and Prevalence Worldwide in 2012

Maximizing the Value of Enzalutamide for Prostate Cancer Patients

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*1 Prostatectomy, radiotherapy
*2 Non-metastatic biochemically recurrent prostate cancer
*3 Non-metastatic castration-resistant prostate cancer
*4 Metastatic hormone-sensitive prostate cancer

Clinical Development Program #2
Gilteritinib (Acute myeloid leukemia)

Acute myeloid leukemia (AML) is the most common form of adult leukemia and requires urgent medical treatment. The prognosis for patients with FLT3*-positive AML is generally worse than other types of AML.
Besides inhibiting FLT3, gilteritinib also inhibits AXL, which is reported to be associated with resistance to some forms of chemotherapy. A comprehensive Phase 3 program for FLT3-positive AML is being conducted with gilteritinib. This includes studies in relapsed and refractory AML as well as in patients receiving low-intensity chemotherapy and after transplantation.

*A receptor-type tyrosine kinase involved in cancer cell proliferation

Gilteritinib in the AML Treatment Landscape

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Clinical Development Program #3
ASP8273 (Non-small cell lung cancer)

Astellas has Tarceva indicated for non-small cell lung cancer (NSCLC). It is known that first-generation drugs of this type can induce resistance over time, and ASP8273 has efficacy in these types of resistance mutations. With its high selectivity for mutated receptors over wild-type receptors, ASP8273 is expected to have an improved safety profile compared to the first-generation epidermal growth factor receptor tyrosine kinase inhibitors.
A Phase 3 trial for ASP8273 as a first-line NSCLC therapy is underway. Further studies in Japan and Asia for ASP8273 as a second-line therapy are being considered as well.

Status of Development

U.S./Europe/Japan/Asia Developing first-line indications Japan/Asia Considering development of second-line indications

Our development approach has been rapid with gilteritinib as we look to satisfy unmet medical needs.

Gilteritinib was originally discovered with the intent of treating a different type of cancer, but molecular activity screens revealed its strong inhibition of FLT3, a target for AML, as well as the related resistance mutation. In Phase 1 we were able to demonstrate clinical response and identify a dose for advancement into later stages of development. This enabled us to move directly from Phase 1 to Phase 3 in 2 years. The data were promising enough to be selected for SAKIGAKE designation in Japan.
The investigators express strong expectations for the drug’s potential. Our team members are excited that we can provide novel therapeutic options to AML patients. Because gilteritinib also inhibits AXL, it has the potential to treat tumor types other than AML. We are making every effort to deliver gilteritinib to patients worldwide who can benefit from it as soon as possible.

Portrait of Itsuro Nagase D.V.M., Ph.D.

Itsuro Nagase
D.V.M., Ph.D.
Senior Director
Global Development
Project Leader

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