MADRID—The recombinant factor IX (FIX) product CB 2679d/ISU304 can increase FIX levels in patients with severe hemophilia B, according to a phase 1/2 trial.
Results showed a continuous linear increase in FIX activity levels following daily subcutaneous (SQ) dosing of CB 2679d for 6 days.
Adverse events were mild to moderate, and none of the patients have developed inhibitors to CB 2679d or FIX.
Howard Levy, MB ChB, PhD, chief medical officer of Catalyst Biosciences, Inc., presented these results at the 11th Annual Congress of The European Association for Haemophilia and Allied Disorders (EAHAD).
The research was sponsored by Catalyst Biosciences, Inc.
This phase 1/2 trial was divided into 5 cohorts.
In cohort 1, researchers compared single doses of intravenous (IV) CB 2679d and IV BeneFIX (recombinant FIX). CB 2679d proved 22 times more potent than BeneFIX. The products’ half-lives were 27.0 hours and 21.0 hours, respectively.
In cohorts 2 and 3, researchers compared single, ascending doses of IV CB 2679d to SQ CB 2679d. The bioavailability of SQ CB 2679d was 18.5%, and the half-life was 98.7 hours.
Cohort 4 was dropped, as it was another comparison of IV and SQ CB 2679d, which was considered unnecessary.
Cohort 5 included 5 patients who received daily doses of SQ CB 2679d. For 6 days, patients received CB 2679d at a dose of 140 IU/kg SQ.
The patients’ FIX activity levels increased from a median of <1% at baseline to a median of 15.7% (interquartile range, 14.9% to 16.6%) after all 6 doses.
The increase in FIX activity levels after the daily dosing was linear, indicating that continued SQ dosing may increase FIX activity further.
The median half-life was 63.2 hours (interquartile range, 60.2 to 64 hours), with the result that activity levels were still at 4% to 6.4% five days after the last dose.
No inhibitors to CB 2679d or FIX were observed in any of the cohorts in this trial.
In cohort 5, adverse events included pain, erythema, redness, and bruising after injections. Bruising occurred only with initial injections, and the severity of pain, erythema, and redness decreased over time (from moderate to mild).
“Existing IV therapies have FIX trough levels that can drop as low as 1% to 3% before repeat dosing,” Dr Levey said. “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 6 days of treatment, CB 2679d compares favorably to currently approved therapies for hemophilia B, all of which are infused IV.”