Bioverativ announced the first patient has been dosed in the Phase 3 clinical program of its investigational therapy BIVV009 for cold agglutinin disease (CAgD). The Phase 3 program includes two parallel Phase 3 trials, Cardinal and Cadenza, which are evaluating the efficacy and safety of BIVV009 in adult patients with primary CAgD, a disease with no approved therapies.
CAgD is a rare blood disease that results in the premature destruction of red blood cells (hemolysis) by the body’s immune system. People with CAgD suffer from anemia, which is often severe, and can experience profound fatigue, and/or a significantly increased risk of life-threatening thromboembolic (TE) events such as stroke, pulmonary embolism, and heart attack. Recently-presented results from the CAgD Optum study, the largest retrospective study of cold agglutinin disease, showed that CAgD patients had a 55% overall increased rate of TE events versus matched controls (31% vs. 20% p<0.0001), as well as a statistically significant higher frequency of multiple TE events.
“I am optimistic that the initiation of the Phase 3 trials of BIVV009 moves us closer to a new era of treatment for people living with cold agglutinin disease,” said Catherine Broome, M.D., Associate Professor, Georgetown University. “People with cold agglutinin disease can suffer from a significant disease burden, and data from the Phase 1 study suggests that BIVV009 may be able to address the underlying hemolysis, which is at the core of the disease.”
The Cardinal trial, in which the patient was dosed, is an open-label, single-arm study that will evaluate the safety and efficacy of BIVV009 in 20 adult patients with primary CAgD who have had at least one recent blood transfusion. The Cadenza trial is a randomized, double-blind, placebo-controlled study that will evaluate the safety and efficacy of BIVV009 in 40 adult patients with primary CAgD who have not recently had a blood transfusion. For more information about the Phase 3 studies, visit clinicaltrials.gov (study numbers: NCT03347396 and NCT03347422).
BIVV009 is a novel monoclonal antibody that has been designed to block C1s in the classical complement pathway and directly target the root cause of cold agglutinin disease. It is believed that this approach may prevent the complement system, which is a part of the immune system, from mistakenly destroying a person’s red blood cells, and potentially halt the CAgD disease process.
BIVV009 was awarded Breakthrough Therapy Designation by the U.S. Food and Drug Administration (FDA) and Orphan Drug Designation by both the FDA and European Medicines Agency. These designations acknowledge the potential of novel drugs and biologics, and are intended to expedite the development and regulatory review of such therapies.
The Phase 1b study assessed the long-term efficacy, safety, and PK/PD profile of BIVV009 in six severely anemic primary CAgD patients. Primary and secondary outcome measures were achieved in the CAgD patients in the study. Hemoglobin levels increased in all six patients (median >4g/dl), eliminating the need for transfusions while on treatment. Maintenance therapy through a Named Patient Program has demonstrated a sustained response for more than 18 months, including control of hemolysis. Safety data through December 21, 2016, demonstrated that BIVV009 was generally well tolerated. Five of six patients (83.3%) in the primary CAgD group experienced at least one adverse event (AE); no AE was reported by more than one patient. One unrelated, serious AE occurred in a patient with CAgD who was hospitalized for a pre-existing condition. There were no serious AEs assessed as related to BIVV009 by the investigator.
CAgD is a severe, chronic rare blood disease in which a part of the body’s immune system called the complement system mistakenly attacks a person’s own red blood cells. People with CAgD suffer from chronic anemia, severe fatigue, and an increased risk of life-threatening events such as stroke. There are no approved therapies for CAgD, which occurs in approximately 16 people per million, including an estimated 10,000 people in the United States and Europe. Current treatment options are aimed at normalizing hemoglobin levels through blood transfusions, immunomodulating therapy not approved for CAgD, or chemotherapy using cytotoxic agents. These options have significant toxicity risks and are often nondurable, leaving patients dependent on frequent transfusions, which can lead to chronic iron overload. Learn more about CAgD.
BIVV009 is a first-in-class, humanized, monoclonal antibody that has been specifically designed to target C1s, a serine protease within the C1-complex, that is the first step in activating the classical complement pathway of the immune system. The classical complement pathway is the central mechanism responsible for the development of hemolytic anemia in cold agglutinin disease and blocking it may potentially halt the CAgD disease process. With a novel mechanism of action and high target specificity, BIVV009 is designed to selectively inhibit disease processes upstream in the classical complement pathway while leaving intact the alternative and lectin complement pathways and their immune surveillance functions.