First Patient Dosed in Phase 3 of Cold Agglutin Disease Therapy

This morning, it was announced that the first patient was diagnosed in Bioverativ’s Phase 3 clinical program of the investigational therapy BIVV009 for the treatment of cold agglutinin disease (CAgD).

The program consists of two parallel trials — Cardinal and Cadenza – both of which are evaluating the safety and efficacy of BIVV009 in adult patients with primary CAgD, a disease which, at present, doesn’t have any therapies approved by the U.S. Food and Drug Administration (FDA).

CAgD is commonly associated with severe anemia, and is characterized by its symptoms, like crippling fatigue and an increased risk of life-threatening thromboembolic (TE) events, such as pulmonary embolism and stroke. The rare blood disease results in the premature destruction of red blood cells, or hemolysis, by the body’s immune system.

BIVV009 is being developed to directly target the root of CAgD by blocking a serine protease within the C1 complex (C1s) in the classical complement pathway. The novel monoclonal antibody has been granted both Orphan Drug Designation and Breakthrough Therapy Designation by the FDA.

Results from the CAgD Optum study were presented at the 59th American Society of Hematology (ASH) Annual Meeting and Exposition in December, and showed that CAgD patients had a 55% overall increased rate of TE events compared to matched controls (31% vs. 20% p<0.0001), as well as a statistically significant higher frequency of multiple TE events.¹

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 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.

“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 in a press release. “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 classical complement pathway in which the potential therapy operates is the central mechanism responsible for the development of hemolytic anemia in this patient population, and it is expected that blocking it could potentially prevent progression of the disease.

Rare Disease Report caught up with Maha Radhakrishnan, M.D., Senior Vice President of Medical for Bioverativ Therapeutics, at the 59th ASH Annual Meeting and Exposition. In the video below, she discusses the unmet need for treatments of CAgD, and rare diseases in general:

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References

1. Broome, C., et al. Incidence of Thromboembolic Events Is Increased in a Retrospective Analysis of a Large Cold Agglutinin Disease (CAD) Cohort. 59th Annual Meeting of the American Society of Hematology; December 9-12, 2017; Atlanta.