Under-the-skin, preventive treatment with Dalcinonacog alfa (DalcA) led to sustained and protective levels of factor IX (FIX) in people with severe hemophilia B, final data from a Phase 2b trial show.
The findings, Phase 2b Trial to Evaluate the Safety and Factor IX Levels of a Daily Subcutaneous Prophylaxis Treatment Regimen of Dalcinonacog alfa in Hemophilia B,” were presented by Howard Levy, PhD, chief medical officer at Catalyst Biosciences, at the World Foundation of Hemophilia Virtual Summit. The summit is being held online, with free live and recorded sessions, from June 14-19.
DalcA is a lab-made version of the blood clotting protein FIX — whose deficiency causes hemophilia B — that works as a prophylactic (preventive) treatment for bleeding episodes.
The experimental treatment can be given via subcutaneous, or under-the-skin injections, instead of the more invasive intravenous (into-the-vein) delivery of other FIX therapies.
In the open-label, Phase 2b DLZ-201 trial (NCT03995784), six men with severe hemophilia B received one intravenous DalcA loading dose of 50 international units (IU)/kg, followed by daily subcutaneous injections of 100 IU/kg for 28 days.
A five-day washout period included daily measures of the treatment’s safety and pharmacological profile. Of note, a washout period is the time between treatment sessions, in which the medication “washes out” of the body and thus won’t affect measurements taken during the subsequent period.
The study’s main goal was to assess the required DalcA dose needed to increase steady-state FIX activity levels above 12%. The therapy’s safety, tolerability, and immunogenicity — whether it induces an immune response — also were evaluated. The trial also examined DalcA’s pharmacodynamics, or how it affects the body, as well as its pharmacokinetics, which is how the body affects the treatment.
Early data had shown that DalcA was effective as a preventive treatment. No bleeds were detected and steady-state FIX activity up to 27% was seen after 14 days.
In addition, the treatment was found to be well-tolerated, with two moderate adverse reactions that resolved without further complications. One was an injection site reaction and the other a hematoma, or localized bleeding outside of a blood vessel.
Updated trial results showed that, after 28 days of daily under-the-skin dosing, all participants achieved protective FIX levels above 12%. Steady-state levels of FIX were detected after two weeks. By day 29, the mean FIX activity was of 19.4%, which exceeded the 12% goal.
DalcA’s half-life — the time for the concentration of a compound in the body to drop by half — ranged from 2.5 to 5.1 days, with no bleeds during treatment or the washout period. According to Catalyst, such results support DalcA as an effective preventive therapy that may enable lower or less frequent dosing than existing alternatives.
“Subcutaneous DalcA prophylaxis provided continuously protective levels of FIX,” the investigators wrote.
The researchers also found no evidence of an immune response against DalcA, which could have limited the therapy’s effectiveness.
No serious adverse side effects were reported. One participant dropped out on day seven due to injection site reactions after the first three subcutaneous doses. Some participants developed mild injection site reactions, including pain and/or redness, mainly following the first injections.
No blood clotting events were reported. Likewise, no relevant alterations in four blood-clotting markers were observed. Sporadic increases in a marker called D-dimer decreased with continued dosing.
“The trial data showed excellent efficacy and a clean safety profile, all subjects achieved steady state FIX activity levels exceeding the primary endpoint of 12%,” Nassim Usman, PhD, president and CEO of Catalyst, said in a press release.
“A simple, small volume SQ [subcutaneous] therapy to provide protective, FIX levels is a potentially transformational improvement in the management of Hemophilia B,” Usman said.
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