Catalyst Biosciences has announced new clinical data supporting the safety and efficacy of its lead candidate therapies for treating hemophilia. Factor IX (FIX) dalcinonacog alfa (DalcA) was found to safely prevent bleedings in adults with hemophilia B, while factor VIIa (FVIIa) marzeptacog alfa (activated) (MarzAA) was shown to be safe and effective in treating acute bleeds in those with hemophilia A or B with or without inhibitors.
The updates were presented at the 13th Annual Congress of the European Association for Haemophilia and Allied Disorders (EAHAD), held Feb. 5-7 in the Hague in the Netherlands.
DalcA’s trial data were detailed in an oral presentation titled “Phase 2B Trial to Evaluate the Safety and Factor IX Levels Resulting from a Daily Subcutaneous Prophylaxis Treatment Regimen of Dalcinonacog Alfa (DalcA) in Hemophilia B.” It was given by Johnny Mahlangu, the study’s principal investigator, a professor of hematology and the head of the school of pathology at the University of Witwatersrand, in South Africa.
The trial is taking place at the Haemophilia Comprehensive Care Centre in Johannesburg.
DalcA (CB2679d) is a recombinant, or lab-made clotting factor IX designed to serve as a prophylactic therapy to prevent or lessen bleedings in people with hemophilia B. It was specifically engineered to have a 22‐fold greater potency and a longer half‐life compared with the natural version of factor IX.
Unlike other clotting factor products, which are delivered directly into the vein — called intravenous injections — DalcA is administered by injections under the skin, known as a subcutaneous injection. The subcutaneous injection is a less invasive method that allows at-home treatment.
The open-label Phase 2b trial (NCT03995784) is evaluating the ability of DalcA to maintain stable and protective FIX levels — meaning levels above 12% — in six people with severe hemophilia B.
The participants received a single intravenous dose of DalcA, followed by daily subcutaneous doses for 28 days. The trial’s latest results show that 28 days of DalcA are able to provide stable therapeutic levels of FIX, reaching up to 27% after 14 days of treatment.
As of the data cutoff on Feb. 5, no bleeds had been observed.
In addition, no inhibitors — anti-drug antibodies that render the treatment ineffective — were detected and no serious adverse events were reported. Three participants reported reactions at the injection site, such as pain, redness, and swelling, but most were mild and went fully resolved. One patient left the study due to moderate injection reactions.
Taken together, the data demonstrate that DalcA is able to provide stable therapeutic levels of the clotting factor and has “potential to be an effective prophylaxis treatment” for hemophilia B. Its extended half-life may allow lower or less frequent dosing, the researchers noted.
“The DalcA Phase 2b trial data presented today at EAHAD clearly demonstrate the potential for DalcA to significantly change the treatment paradigm for those suffering from hemophilia B,” Nassim Usman, PhD, president and CEO at Catalyst, said in a press release.
“With the trial now fully enrolled and one final subject completing dosing, we will announce final data in the second quarter of this year,” Usman said.
Along with the data from the DalcA trial, Catalyst also presented the most recent findings from its other candidates for hemophilia.
One poster, titled “Phase 1 study to evaluate the pharmacokinetics, pharmacodynamics, and safety of ascending doses of subcutaneous marzeptocog alfa (activated) in adult subjects with hemophilia,” highlighted results from a Phase 1 trial (NCT04072237) expected to enroll eight participants. That trial is evaluating the pharmacokinetics — availability in the body — pharmacodynamics, or drug effects, and the safety of increasing doses of subcutaneous MarzAA in adults with hemophilia A or B, with or without inhibitors.
MarzAA is a new lab-made factor VIIa designed for long-term prevention of bleeding episodes in people with hemophilia with inhibitors, as well as those with acquired hemophilia and other bleeding disorders. It is designed to have increased potency to rapidly achieve therapeutically relevant concentrations in the blood, and could be used for under-the-skin prophylactic treatment and under-the-skin or into-the-vein acute treatment of bleeds.
The study’s latest results show that subcutaneous injections of MarzaAA are well-tolerated and rapidly raise and maintain factor VIIa levels at concentrations required to treat acute bleeds in patients with and without inhibitors.
Preclinical data presented in another poster, titled “Fast Onset of Action of Subcutaneously Administered Marzeptacog Alfa (Activated) Supports On-Demand Treatment in Hemophilia A Mice,” showed that subcutaneous MarzAA was as efficient as intravenous injection with the bypassing agent NovoSeven (recombinant FVIIa; eptacog alfa, activated).
Both MarzAA and Novo Nordisk‘s NovoSeven were effective in treating bleedings in hemophilia A mice, the data showed.
Thus, subcutaneous MarzAA “can potentially be used on-demand to treat acute bleeding,” the researchers said. However, they stressed that these early results warrant further clinical investigation.
“We are very encouraged by the data presented at EAHAD from three of our programs and see 2020 as a pivotal year for our entire hemophilia franchise,” Usman said.
“In addition to the Phase 2b DalcA data, our SQ FVIIa marzeptacog alfa (activated) MarzAA candidate has demonstrated efficacy and safety in individuals with hemophilia A or B with inhibitors in a Phase 2 prophylaxis study, and this week we presented pharmacokinetic and pharmacodynamic data that support SQ MarzAA use in acute or on-demand settings,” he added.
Catalyst also shared early results on its hemophilia B gene therapy candidate, CB 2679d-GT. Optimization efforts focused on the delivery vector, an AAV capsid, may lower the dose required for achieving protective FIX activity levels by 10-fold or greater.
“Our high-potency FIX gene therapy candidate, CB 2679d-GT is developing into a promising asset with encouraging pre-clinical data using a proprietary next-generation AAV capsid. Our entire team is committed to developing novel treatments in multiple rare bleeding disorders,” Usman said.
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