Mast Therapeutics, Inc., a biopharmaceutical company developing novel, clinical-stage therapies for sickle cell disease and heart failure, announced that it has completed patient enrollment in its phase 3 clinical study of vepoloxamer for the treatment of patients with sickle cell disease experiencing vaso-occlusive crisis, known as the EPIC study. Consistent with prior guidance, the company expects to report top-line results in the second quarter of 2016.
The EPIC study was conducted under the direction of principal investigator James F. Casella, M.D., Rainey professor and chief, Division of Pediatric Hematology, vice chair for research, Pediatrics and director of the Basic and Translational Research Program in Sickle Cell Disease, Comprehensive Sickle Cell Center at Johns Hopkins University School of Medicine.
"The full enrollment of EPIC is an important achievement in the history of sickle cell disease clinical development, as it represents the largest placebo-controlled clinical trial conducted to date for our patients with this disease," stated Mark T. Gladwin, M.D., Jack D. Myers professor and chair, chairman of the department of medicine, director, Pittsburgh Heart, Lung, Blood and Vascular Medicine Institute, UPMC and the University of Pittsburgh School of Medicine, and member of the Executive Steering Committee for EPIC.
"Interventional treatment of acute painful crisis represents an important unmet medical need, and has remained elusive to large, multicenter randomized trials necessary to support registration of a new drug. EPIC has set a new standard for the field, and the learnings from this study will have an important impact on the design of future studies. The patients and their families, our committed clinical investigators, and Mast Therapeutics should be applauded for this important achievement."
"As physicians, we are frustrated by our inability to offer patients a disease-modifying treatment for an ongoing crisis," stated Gregory J. Kato, M.D., professor of medicine, Division of Hematology/Oncology, director, Sickle Cell Center of Excellence, UPMC and the University of Pittsburgh School of Medicine, and member of the Executive Steering Committee for EPIC.
"This is a challenging condition for which multiple underlying pathologies may need to be addressed simultaneously to achieve clinical outcomes. In non-clinical studies, vepoloxamer has demonstrated multiple activities that may improve the complex pathologies occurring during sickle cell crisis. We are anxious to review the data from the trial, once unblinded, to determine how vepoloxamer's pharmacodynamic activity translates to clinical benefit for sickle cell patients."
"We are proud to have completed enrollment in the EPIC study," stated Brian M. Culley, chief executive officer. "We wish to express our deep gratitude to the courageous patients and their family members and the committed investigators and study coordinators around the globe who have helped us achieve this goal."
"Following the last patient's discharge from the hospital and 30-day safety observation period, there will be an extensive and rigorous review of the blinded data for quality control, ultimately leading to database lock. Study unblinding then will be performed by the study biostatistician. After the biostatistician's work is complete, Mast will learn the top-line outcome of the study from the biostatistician and will be able to report top-line results to the public," continued Culley.
The EPIC study is a randomized, double-blind, two-arm, placebo-controlled, phase 3 clinical trial of vepoloxamer in patients with sickle cell disease hospitalized for treatment of vaso-occlusive crisis. The primary objective of the study is to demonstrate that vepoloxamer reduces the duration of vaso-occlusive crisis, with the duration of crisis measured from the time a patient is randomized to the time at which the patient receives the last dose of parenteral opioid analgesic for the treatment of vaso-occlusive crisis prior to hospital discharge. A total of 388 patients, ages four to 46 were enrolled in EPIC. Secondary efficacy endpoints are to compare the rates of re-hospitalization for vaso-occlusive crisis within 14 days of initial hospital discharge and the occurrence of acute chest syndrome within 120 hours of randomization between the treatment and control groups.
Sickle cell disease is a chronic, genetic blood disorder that affects millions worldwide and an estimated 90,000 to 100,000 people in the United States, where it is classified as a rare, or orphan, disease. The hallmark of sickle cell disease is recurring episodes of severe, debilitating pain commonly known as sickle cell crisis or vaso-occlusive crisis. The intense pain experienced by patients is the result of obstruction of blood vessels by "sickled" red blood cells, which are rigid and highly adherent to the vessel walls and to each other. This obstruction leads to reduced blood flow to organs, including the bone marrow, not only causing severe pain, but also cumulative tissue damage and, ultimately, loss of vital organ function and significantly reduced lifespan. There are between 80,000 to 100,000 hospitalizations annually in the US related to vaso-occlusive crisis and no approved treatment option to shorten the duration or reduce the severity of a crisis once underway.