Biogen Idec and Swedish Orphan Biovitrum ( Sobi ) have announced positive results from B-LONG, a clinical study that evaluated a new long-lasting clotting factor candidate in people with hemophilia B.
Hemophilia B is a rare inherited disorder that impairs blood coagulation. Currently, prophylactic treatment of hemophilia B requires intravenous injections up to three times a week.

Results from B-LONG has shown that rFIXFc ( long-lasting recombinant Factor IX Fc fusion protein ) was effective in the control and prevention of bleeding, routine prophylaxis, and perioperative management.

B-LONG was a global, open-label, multi-center phase 3 study that evaluated the efficacy, safety and pharmacokinetics of intravenously-injected rFIXFc. The study was designed to evaluate rFIXFc in the control and prevention of bleeding, routine prophylaxis and perioperative management in patients with hemophilia B.

The B-LONG study had four treatment arms. In Arm 1 ( weekly prophylaxis; n=63 ), patients were treated weekly with a starting dose of 50 IU/kg, which was adjusted to maintain trough factor levels sufficient to prevent bleeding. In Arm 2 ( individualized interval prophylaxis; n=29 ), patients were treated with 100 IU/kg, at an initial interval of 10 days, which was subsequently individualized to maintain trough factor levels sufficient to prevent bleeding. In Arm 3 ( episodic treatment; n=27 ), patients received rFIXFc episodic treatment as needed for bleeding. In Arm 4 ( perioperative management; n=12 patients ), rFIXFc was evaluated in the surgical setting; 8 patients in the surgery arm were also enrolled in other treatment arms.

The primary efficacy and safety measures were the annualized bleeding rate and the incidence of adverse events and inhibitor development in patients studied for up to 77 weeks. Secondary endpoints included response to treatment of bleeding episodes and the pharmacokinetics of rFIXFc versus BeneFIX.

In the B-LONG study, 123 male patients aged 12 years and older were enrolled. Overall, 93.5 percent of patients completed the study.

Recombinant FIXFc was generally well-tolerated. No inhibitors to rFIXFc were detected and no cases of anaphylaxis were reported in any patients, all of whom switched from commercially-available Factor IX products. One serious adverse event was assessed to be possibly related to drug by the investigator. The patient experienced obstructive uropathy in the setting of hematuria; he continued rFIXFc treatment and the event resolved with medical management.

The most common adverse events ( incidence of greater than or equal to 5% ) occurring outside of the perioperative management arm ( i.e., Arms 1, 2 and 3, but not Arm 4 ) were nasopharyngitis, influenza, arthralgia, upper respiratory infection, hypertension and headache.

The overall median annualized bleeding rates ( including spontaneous and traumatic bleeds ) were 2.95 in the weekly prophylaxis arm, 1.38 in the individualized interval prophylaxis arm, and 17.69 in the episodic treatment arm. In the individualized interval prophylaxis arm, the median dosing interval during the last 6 months on study was 14 days.

Control of bleeding was assessed in all patients who experienced a bleeding episode during the study. Overall, 90.4% of bleeding episodes were controlled by a single injection of rFIXFc.

Recombinant FIXFc was assessed in the perioperative management of 12 patients undergoing 14 major surgical procedures. The treating physicians rated the hemostatic efficacy of rFIXFc as excellent or good in 100 percent of these surgeries.

B-LONG included a pharmacokinetic ( PK ) analysis of rFIXFc in all patients in the study. In a protocol-defined subset of patients with extensive PK sampling, the approximate terminal half-life of rFIXFc was 82 hours compared to 34 hours for BeneFIX, an recombinant coagulation Factor IX.

Recombinant FIXFc is a clotting factor developed using monomeric Fc fusion technology, which makes use of a natural pathway to recycle rFIXFc in circulation and enable it to remain in the body longer. With this technology, rFIXFc is designed to provide long-lasting protection from bleeding and reduce the treatment burden associated with hemophilia B, which currently requires more than 100 injections annually for prophylaxis with commercially-available Factor IX products.

Hemophilia B is a rare, inherited disorder in which the ability of a person's blood to clot is impaired. Hemophilia B occurs in about one in 25,000 male births annually and is caused by having substantially reduced or no Factor IX activity, which is needed for normal blood clotting. People with hemophilia B therefore need injections of Factor IX to restore the coagulation process and prevent frequent bleeds that could otherwise lead to pain, irreversible joint damage and life-threatening hemorrhages.

Source: Biogen Idec, 2012

XagenaMedicine2012