Treatment with CB 2679d increased factor IX activity levels in the blood, bringing them closer to normal levels in the newest group of patients with severe hemophilia B in the Phase 1/2 FIX clinical trial, Catalyst Biosciences announced in a press release.
Catalyst, the therapy’s maker, believes that the next-generation factor IX candidate may be used as a preventive strategy for those with hemophilia B.
Hemophilia B patients lack the clotting protein factor IX, leading to severe and spontaneous bleeding episodes. Currently approved therapies rely on frequent intravenous infusions, and are unable to steadily normalize factor IX levels and activity.
The Phase 1/2 trial (NCT03186677) is taking place at three centers in South Korea under the supervision of Catalyst’s collaborator, ISU Abxis.
In the first three groups of patients, the trial investigated the safety, overall stability, and patient response to the therapy given as a single intravenous (in the vein) administration followed by subcutaneous (under the skin) dosing.
Another group, cohort 5, received daily subcutaneous injections of CB 2679d without an intravenous dose. Catalyst amended the trial in January to remove cohort 4.
In April, the trial was amended again to add a sixth group of patients receiving a single intravenous dose of CB 2679d (administered at 75 IU/kg) followed by nine daily subcutaneous doses (150 IU/kg) of CB 2679d within 30 minutes of the intravenous dose.
Cohort 6 has enrolled two patients — the target is three to five patients — and the new data shows that after the single intravenous dose, factor IX activity levels consistently remained above 20% in both patients.
Factor IX activity levels progressively increased to 34% in the first patient and 31% in the second patient, both of which fall within the range considered mild hemophilia, which the World Federation of Hemophilia classifies as levels from 5% to 40%. The two patients have not had any bleeds or adverse effects, and are being closely monitored.
Follow-up blood analysis of both patients showed the presence of inhibitors, or neutralizing antibodies, occurring transiently in the first patient, but none of the antibodies targeted the natural factor IX, allowing the participants to resume their preventive FIX therapies. Inhibitors were only detected in cohort 6, and Catalyst is investigating the source of these inhibitors and their impact to the treatment prior to dosing more patients in this group.
“The most recent data from the ongoing Phase 1/2 trial have demonstrated clinical proof of concept for subcutaneous dosing of a potent FIX as a treatment for hemophilia B. Patients in Cohort 6 of the trial were able to maintain Factor IX levels over 30% which is at the upper end of mild hemophilia and higher than currently approved extended half-life (EHL) intravenous Factor IXs,” Nassim Usman, PhD, CEO of Catalyst, said in the release.
“Our next steps will be to carefully identify the cause and nature of the antibodies and provide further updates once we have the results of our analysis,” Usman said.
The European Commission and U.S. Food and Drug Administration granted orphan drug designations to CB 2679d in 2017.
Catalyst Biosciences is also conducting an ongoing Phase 2 clinical trial (NCT0340765) investigating marzeptacog alfa (activated), also known as MarzAA, as a preventive treatment for hemophilia A or B with inhibitors.
The FDA granted MarzAA orphan drug status as a therapy for preventing bleeding episodes in hemophilia A or B patients with inhibitors.