DALLAS—Results of 3 studies suggest the full-length recombinant factor VIII product BAY 81-8973 can be safe and effective in children, adolescents, and adults with severe hemophilia A.
Patients who received BAY 81-8973 as routine prophylaxis had low annualized bleeding rates (ABRs)—significantly lower than patients who received on-demand treatment.
None of the patients developed inhibitors, and no adverse event occurred in more than 10% of patients.
These results were presented in posters at the National Hemophilia Foundation’s 67th Annual Meeting. All 3 trials were sponsored by Bayer Healthcare AG, the company developing BAY 81-8973.
LEOPOLD trials
The 3 trials are part of the LEOPOLD Clinical Development Program, which was designed to evaluate BAY 81-8973 in patients with severe hemophilia A.
The first trial, LEOPOLD I, included male patients ages 12 to 65 who had at least 150 previous exposure days with a factor VIII product. For this study, they received BAY 81-8973 at 20-50 IU/kg 2 or 3 times a week (according to investigator decision) for 12 months.
The second trial, LEOPOLD II, also enrolled previously treated (≥ 150 previous exposure days) male subjects ages 12 to 65. The subjects were randomized to receive BAY 81-8973 as a low-dose prophylaxis regimen (20-30 IU/kg) twice a week, high-dose prophylaxis (30-40 IU/kg) 3 times a week, or on-demand.
In the third trial, LEOPOLD Kids, researchers evaluated BAY 81-8973 in previously treated children ages 12 and younger. Patients received BAY 81-8973 at 20-50 IU/kg twice a week, 3 times a week, or every other day (according to investigator decision) for at least 50 exposure days.
Another part of LEOPOLD KIDS, in which researchers are evaluating BAY 81-8973 in previously untreated children, is ongoing.
Efficacy results
The ABR was the primary efficacy endpoint in LEOPOLD I and II. In LEOPOLD KIDS, the primary efficacy endpoint was the ABR for total bleeds occurring within 48 hours of previous prophylaxis treatment, but the researchers also analyzed the ABR independent of the time of injection.
For all 3 trials, 193 patients were evaluable for efficacy. One hundred and forty patients received BAY 81-8973 for 12 months or more. The median exposure days were 155 for LEOPOLD I and 153 for LEOPOLD II.
In LEOPOLD I (n=62), the median ABR was 1.0 for all patients who received prophylaxis, 1.0 for patients who received twice-weekly prophylaxis, and 2.0 for patients who received thrice-weekly prophylaxis.
Sixteen patients did not experience any bleeds while on study—6 patients on the twice-weekly prophylaxis regimen and 10 on the thrice-weekly prophylaxis regimen.
LEOPOLD II included 28 patients who received twice-weekly prophylaxis, 31 who received thrice-weekly prophylaxis, and 21 who received on-demand treatment.
The median ABR was significantly lower in patients who received either prophylactic regimen than those who received on-demand treatment—2.0 and 60.0, respectively (P<0.0001). The median ABR was 4.0 for patients who received twice-weekly prophylaxis and 2.0 for patients who received thrice-weekly prophylaxis.
Again, 16 patients who received prophylaxis did not have any bleeds during the study period. This included 8 patients on the twice-weekly prophylaxis regimen and 8 on the thrice-weekly prophylaxis regimen.
In LEOPOLD KIDS (n=51), the median ABR within 48 hours of prophylactic injection was 0, and the median ABR independent of the time of injection was 1.9.
Twenty-three patients did not have any bleeds during the 6-month treatment period—10 children younger than 6 and 13 children ages 6 to 12.
Safety results
For all 3 trials, 193 patients were evaluable for safety. Adverse reactions were defined as treatment-emergent adverse events with
at least a reasonable suspected causal relationship to BAY 81-8973.
The researchers said the frequency, type, and severity of adverse reactions in children were similar to those observed in adults and adolescents.
The adverse reactions included headache (7.3%), pyrexia (4.1%), pruritus (3.1%), injection site reactions (2.6%), insomnia (2.6%), rash (2.6%), abdominal pain (2.1%), dyspepsia (2.1%), abdominal discomfort (1.6%), lymphadenopathy (1%), dizziness (1%), allergic dermatitis (1%), heart palpitations (1%), sinus tachycardia (1%), chest discomfort (1%), hypersensitivity (0.5%), dysgeusia (0.5%), urticaria (0.5%), and flushing (0.5%).
None of the patients developed factor VIII inhibitors.
