Catalyst Biosciences Announces Positive Top-Line Data for Potential Hemophilia B Treatment
Novel Protease Drug
Catalyst Biosciences, Inc., a clinical-stage biopharmaceutical company focused on developing novel medicines to address hematology indications, announced top-line data from its Phase 1/2 study of subcutaneous (SQ) prophylactic candidate CB 2679d/ISU304 being developed for the treatment of hemophilia B in an oral presentation at the 11th Annual Congress of The European Association for Haemophilia and Allied Disorders (EAHAD) in Madrid. Results from the trial showed a continuous linear increase in Factor IX (FIX) activity levels following daily dosing of CB 2679d for six days.
“These exciting results demonstrate for the first time the feasibility of a subcutaneous FIX injection to provide meaningful protection from bleeding, even after only six doses,” said Dr. John Pasi, professor of haemostasis and thrombosis at Barts and The London School of Medicine and Dentistry. “As a result, this treatment option has the potential to normalize coagulation activity and dramatically improve the quality of life of individuals affected by hemophilia B.”
Dr. Howard Levy, chief medical officer of Catalyst, presented results from the final cohort of the Phase 1/2 trial of CB 2679d in patients with severe hemophilia B. After six days of once-daily SQ dosing, CB 2679d increased FIX activity levels in 5 patients who were each dosed daily with 140 IU/kg SQ, from very low levels after washout of prior therapy to a median FIX activity level of 16% (range 11.5-18%), that is well into the mild hemophilia range (5-40%), and is higher than a level required to prevent hemarthrosis. The observed increase in FIX activity levels after the daily dosing was linear, indicating that continued SQ dosing may achieve high-mild hemophilia or even normal FIX clotting activity. Terminal SQ half-life was 63.2 hours (interquartile range 60.2-64 hours) with the result that activity levels were still 4-6.4%, 5 days after the last dose. No inhibitors to CB 2679d or FIX were induced to date. One subject had moderate adverse events of pain, erythema and redness after the first 2 injections and mild rating after subsequent injections. Other subjects in cohort 5 reported some of these adverse events, mainly with initial injections. Two subjects had bruising after injection when FIX activity levels were low that did not occur with subsequent injections as FIX activity levels rose. Presentation materials can be accessed here.
Dr. Levy remarked, “Existing IV therapies have FIX trough levels that can drop as low as 1-3% before repeat dosing. Daily subcutaneous dosing of CB 2679d has the potential to minimize the variability in FIX activity levels observed between IV doses and maintain individuals in the mild or even normal hemophilia range. This study demonstrates that, even after just six days of treatment, CB 2679d compares favorably to currently approved therapies for hemophilia B, all of which are infused IV.”