Aligned with our vision to turn innovative science into value for patients, Astellas has focused on exploring new therapeutic areas through a combined approach of homegrown science, strategic partnerships and collaborations with external organizations, and dedicating resources with academia to further enhance our ability to generate potential new treatment options for patients.

As part of this approach, Astellas in 2013 formed a collaboration with Cytokinetics, Inc., a biopharmaceutical company dedicated to discovering and developing novel therapies for people with diseases that compromise key muscle functions.

Astellas and Cytokinetics partnered to advance therapies for diseases and medical conditions associated with muscle impairment and weakness, an area in need of innovation and novel therapies and a new area of focus for Astellas. Astellas’ work with Cytokinetics is in the early to mid-stage development across diseases and conditions of muscle impairment including spinal muscular atrophy (SMA), amyotrophic lateral sclerosis (ALS), chronic obstructive pulmonary disease (COPD) and limited mobility or frailty. 

“The collaboration with Cytokinetics came to fruition based on Astellas’ capabilities, as well as the value we saw in combining the best talent with the best science to address a wide range of conditions,” said Makoto Kashiwa, executive director and head of the frontier diseases therapeutic area.

SMA is a severe neuromuscular disease that occurs in approximately one in every 6,000 to 10,000 live births each year and is one of the most common fatal genetic disorders. SMA manifests in various degrees of severity as progressive muscle weakness, resulting in respiratory and mobility impairment. Life expectancy and disease severity vary by type, with Type I patients having the worst prognosis, with a life expectancy of no more than 2 years. Type II, III and IV patients may have a potentially almost normal life span, but eventually suffer gradual weakness in the proximal muscles of the extremities resulting in mobility issues.

ALS is a progressive neurodegenerative disease that afflicts approximately 30,000 people in the United States and a comparable number of patients in Europe. Approximately 6,000 new cases of ALS are diagnosed each year in the United States. The average life expectancy of an ALS patient is approximately three to five years after diagnosis and only 10 percent of patients survive for more than 10 years. Death is usually due to respiratory failure because of diminished strength in the skeletal muscles responsible for breathing. Few treatment options exist for these patients, resulting in a high unmet need for new therapies to address functional deficits and disease progression.

COPD is a progressive obstructive lung disease that typically includes emphysema and chronic bronchitis. The disease is increasingly common and is the third leading cause of death in the U.S. behind cancer and heart disease. While it is estimated that more than 14 million U.S. adults have been diagnosed with COPD, it is widely underdiagnosed and up to 24 million Americans have evidence of impaired lung function. Therapeutic strategies for the treatment of COPD have primarily focused on improving lung function and addressing airflow limitations caused by bronchial obstructions.  Meanwhile, a substantial unmet need for disease management strategies related to improved exercise tolerance still exists.

“Through our collaboration, we’ve learned so much about muscle disease, the patients living with them and the lack of therapies available,” said Kashiwa. “These diseases are debilitating. They not only take over a person’s body, but they affect their minds and relationships. We’re pleased to be working with an organization that can help us reach the muscle disease community and deliver innovative science that provides value to patients.”

“We share a commitment with Astellas to pursue research and development of skeletal muscle activators for people living with diseases of impaired muscle function who are in need of new therapies,” said Fady I. Malik, MD, PhD, Cytokinetics’ Executive Vice President, Research and Development.

Compounds from the collaboration that are being investigated include:

• CK-2127107: A fast skeletal troponin activator, CK- 2127107 is an investigational drug candidate that is intended to increase the calcium sensitivity of the sarcomere by slowing the rate of calcium release from the regulatory troponin complex of fast skeletal muscle fibers. It is a skeletal muscle compound that is being studied to improve muscle function and physical performance in people with diseases and medical conditions associated with neuromuscular dysfunction, muscular weakness and/or muscle fatigue such as SMA, ALS and COPD. CK-2127107 is the subject of five completed Phase 1 clinical trials in healthy volunteers, which evaluated safety, tolerability, bioavailability, pharmacokinetics, and pharmacodynamics, and is currently in Phase 2 clinical development.
• Tirasemtiv: In 2016, Cytokinetics granted Astellas an option for the development and commercialization of tirasemtiv, a fast skeletal troponin activator, as a potential treatment for people living with ALS. Tirasemtiv is the subject of a large, international Phase 3 clinical trial, called VITALITY-ALS, which completed enrollment in August 2016. The trial is designed to assess effects of tirasemtiv versus placebo on measures of respiratory function and muscle strength in people with ALS. Results from VITALITY-ALS are expected in the second half of 2017. In October 2016, an open-label extension clinical trial called VIGOR-ALS began. The trial is designed to assess the long-term safety and tolerability of tirasemtiv, in patients with ALS who have completed their participation in VITALITY-ALS.

This collaboration has enabled Astellas to deepen our expertise in muscle disease and investigate compounds to continue to serve patients with unmet medical needs.