rVIII-SingleChain appears safe, effective for severe hemophilia A

The novel therapy rVIII-SingleChain demonstrated hemostatic efficacy in surgery and controlled bleeding events in patients with severe hemophilia A, according to clinical study results published in Blood.

The therapy also conferred a low annualized bleeding rate in patients on prophylaxis and appeared well tolerated.

Patients with hemophilia rely on recombinant Factor VIII (rFVIII) products to control bleeding episodes; however, many of these products have short half-lives and must be administered multiple times per week, leading to poor compliance rates.

Ingrid Pabinger, MD, professor at Medical University of Vienna, and colleagues conducted a phase 1 to phase 3 study of rVIII-SingleChain (CSL Behring) — a novel B-domain truncated rFVIII composed of covalently bonded FVIII heavy and light chains — for the treatment of hemophilic bleeding episodes and as routine and surgical prophylaxis.

The study included data from 173 adolescent and adult patients (aged at least 12 years) assigned to prophylaxis (n = 146) or on-demand therapy with rVIII-SingleChain (n = 27).

A total of 848 bleeding events occurred on study and were treated by rVIII-SingleChain (on-demand therapy, n = 590; prophylaxis, n = 258). Forty-three percent of prophylactically treated patients had no bleeding events.

Treatment with rVIII-SingleChain controlled 72.2% (n = 603) of the bleeding events with excellent efficacy, and exhibited good efficacy in 21.6% events (n = 180).

The agent exhibited moderate efficacy in controlling the remaining events (6.2%; n = 52), and no bleeds responded poorly or had no response to rVIII-SingleChain.

Hemostatic control was achieved with a single dose of rVIII-SingleChain in 80.9% of bleeding events, with 12.6% resolved with two doses and 6.5% in three or more doses.

Thirteen patients underwent a total of 16 surgeries on study, using rVIII-SingleChain as prophylaxis. The agent exhibited excellent hemostatic efficacy in 15 surgeries and good hemostatic efficacy in one surgery.

The researchers did not detect any FVIII inhibitors in the overall patient population (0%; 95% CI, 0-2.1), including among patients (n = 120) with 50 or more exposure days (0%; 95% CI, 0-3).

A total of 13,580 injections occurred over the course of the study, 99.3% of which resulted in no patient-reported injection reactions. No severe injection reactions occurred; reactions that occurred were considered very slight (0.5%), slight (0.15%) or moderate (0.05%).

Investigator assessment confirmed patient reports, finding no reaction to 99.8% of assessed injections.

Other treatment-emergent adverse events occurred in 64.9% (n = 113) of patients, 77% of which were mild. The researchers determined that 7.5% (n = 13) of adverse events were treatment related.

The most common adverse events included headache, arthralgia and nasopharyngitis. No patient withdrew due to adverse events, and no clinically relevant thromboembolic events occurred.

“This study, which was designed to reflect clinical practice, demonstrated with a robust dataset that rVIII-SingleChain is highly efficacious in the treatment of bleeding events, routine prophylaxis and in controlling hemostasis in a variety of surgical procedures in adolescents and adults with severe hemophilia A,” Pabinger and colleagues wrote. “The study also demonstrated that rVIII-SingleChain has a favorable safety profile and is well tolerated. Very low annualized bleeding rates in patients on individualized prophylaxis hopefully has the potential to translate into prolonged freedom from debilitating joint disease.” – by Cameron Kelsall

Disclosure: CSL Behring funded this study. Pabinger reports a research grant from CSL Behring, as well as honoraria from Biotest, CSL Behring, Novo Nordisk and Pfizer. Please see the full study for a list of all other researchers’ relevant financial disclosures.