rVIII-SingleChain is an investigational recombinant, single-chain factor VIII being studied in adolescents and adults with hemophilia A. Johnny Mahlangu, MD, University of the Witwatersrand, Johannesburg, South Africa, presented the pharmacokinetic, efficacy, and safety results from the phase 1 rVIII-SingleChain AFFINITY trial [NCT01486927].

This was a large, international, open-label study. Based on investigator judgment, patients were assigned to either prophylaxis or on-demand therapy. For prophylaxis, patients received 20 to 40 IU/kg rVIII-SingleChain every second day or 20 to 50 IU/kg rVIII-SingleChain 2 to 3 times per week. For prophylaxis prior to surgery the regimen was individualized based on the type of surgery. Dose and frequency of rVIII-SingleChain could be adjusted at the investigator’s discretion. The World Federation of Hemophilia recommendation was used to guide the treatment of bleeds.

A total of 174 patients were enrolled, 146 (83.9%) for prophylaxis and 27 (15.5%) for on-demand therapy. These included 120 subjects (68.9%) with > 50 exposure days (EDs) and 52 subjects (29.9%) with > 100 EDs; as a result, there were a total of 14 306 EDs. Among the 174 patients, 132 (75.9%) were enrolled in the extension study. Approximately half of the 174 patients were enrolled in Europe, 12.6% in the United States, 5.7% in Japan, and 32.2% from the rest of the world. The ethnic origins of the patients were white for 126 (72.4%), Asian for 31 (17.8%), black or African American for 14 (8.0%), and others for 3 (1.7%). Fourteen patients (8.0%) were adolescents.

The pharmacokinetic profile was further determined in 27 patients who received either rVIII-SingleChain 50 IU/kg or octocog alfa. Samples were collected at the following time points: before dosing; at 30 minutes, 1 hour, 4 hours, 8 hours, 10 hours, 24 hours, 32 hours, and 48 hours; and 72 hours after receiving the drug. Comparing rVIII-SingleChain with octocog alfa, the former had lower clearance, a greater area under the curve, and a longer half-life.

A total of 848 bleeds were treated during the study period. The treatment was rated as excellent or good in 93.8% of bleeds. A single injection controlled 81% of bleeds, and 94% of bleeds were controlled with 1 or 2 injections.

Eighty-six percent of patients were on prophylactic dosing with a 2- or 3-times-per-week regimen (median doses 30 and 36 IU/kg, respectively). The median annualized bleeding rate in the prophylaxis arm was 1.14, significantly less (P < .0001) than 19.64 in the on-demand arm. The annualized bleeding rates for the 2-times-weekly or 3-times-weekly groups were similar. Patients who received rVIII-SingleChain for prophylaxis before a total of 16 surgeries had a 100% success rate. A median dose of 89.4 IU/kg (range, 40.5 to 108.6) was used on the day of surgery.

Over 99% of injections were administered without reactions, and no inhibitors or anti-CHO antibodies were observed. The most frequent adverse events were nasopharyngitis, arthralgia, and headache. There were 10 serious adverse events, including 1 hypersensitivity reaction that was adequately managed with steroids and antihistamines. Overall, rVIII-SingleChain was considered well tolerated and effective in this study population.