FDA Approves Adynovate for Hemophilia A in Pediatric and Surgical Settings

The US Food and Drug Administration (FDA) has approved Adynovate (PEGylated antihemophilic factor [recombinant]) as a treatment for hemophilia A in pediatric patients under 12 years of age and for both adults and pediatric patients in the surgical setting, based on findings from a phase 3 trial.

In the study for children under age 12, Adynovate met its primary endpoint, which was a lack of inhibitory antibodies developed in untreated patients. The approval for the surgical setting was based on an interim analysis of an ongoing phase 3 study, in which 15 patients with severe hemophilia A had perioperative control of hemostasis during surgical procedures.

“Physicians need additional treatment options for pediatric patients and those undergoing surgery with hemophilia A,” lead investigator, Eric Mullins, MD, research director, Hemophilia Treatment Center, Cincinnati Children’s Hospital Medical Center, said in a statement. “As someone who has routinely seen the benefits of factor replacement in adult patients with hemophilia A, I am pleased to be able to provide Adynovate to more patients.”

Adynovate has an extended circulating half-live compared with previous version of the recombinant antihemophilic factor treatment Advate. Adynovate can effectively be administered on a twice weekly schedule, given the agents extended circulating half-life. The treatment was initially approved by the FDA in November 2015.

In the pediatric study that was instrumental for the new indication, 73 patients were enrolled with 66 receiving prophylactic treatment with Adynovate (32 were under 6 years of age and 34 were aged 6 to <12 years). The mean dose of Adynovate was 51.1 IU/kg (±5.5).

There were no bleed events experienced by 25 patients (38%), with no spontaneous bleed episodes for 44 patients (67%) and no joint bleeding for 48 patients (73%). Of the bleeding events that did occur (n = 70), 82.9% were controlled with one infusion and 91.4% were controlled with one or two infusions. This was labeled as excellent or good control of bleeding for 90% of episodes.

In the perioperative setting, the surgeries included three knee replacements, two arthroscopic synovectomies, one cyst extirpation, one port placement, one gastric band placement, and three multiple tooth extractions, which included one radicular cyst removal. Additionally, there were four minor surgeries. The median perioperative dose of Adynovate was 65 IU/kg and the median postoperative dose was 305 IU/kg.

Blood loss during the procedures was less than or equal to non-hemophilic patients. Additionally, the need for blood components or transfusion was similar in the study compared with expectations for non-hemophilic patients. The median observed intraoperative blood loss, which only 10 patients experienced, was 10.0 mL compared with the predicted average blood loss of 50.0 mL for major surgeries.

“At Shire, we are dedicated to developing innovative therapies for patients living with hemophilia A,” Philip J. Vickers, PhD, Global Head of Research and Development at Shire, the company developing the drug, said in a statement. “Today’s announcement of the new FDA-approved indications for Adynovate in pediatric patients less than 12 years of age and those undergoing surgery underscores our commitment to provide treatment options with proven efficacy profiles to more patients living with hemophilia A.”