Long-Acting Factor IX Product Submitted for Regulatory Review

Novo Nordisk has announced the submission to the FDA of a biologics license application for the approval of nonacog beta pegol, a long-acting glycopegylated recombinant factor IX developed for patients with hemophilia B.

The filing of nonacog beta pegol was based on positive results from the paradigm clinical trial program, which involved 115 patients with severe or moderately severe hemophilia B. Nonacog beta pegol was found to be efficacious in routine prophylaxis, in the treatment of bleeding episodes, and during surgery in adults, adolescents, and children. Moreover, nonacog beta pegol appeared to be well tolerated and no safety concerns were identified.

Compared with standard factor IX products, nonacog beta pegol has a five times longer half-life, according to Novo Nordisk. Patients in the paradigm program achieved a higher level of factor IX in the circulation despite less-frequent dosing of nonacog beta pegol. In phase 3 trials, once-weekly administration of nonacog beta pegol 40 IU/kg maintained factor IX activity levels above 15%, reduced the median annualized bleeding rate (ABR) to 1.0, and showed a potential to prevent bleeds in target joints.

Nonacog beta pegol is a factor IX molecule with an extended half-life intended for replacement therapy in patients with hemophilia B. Glycopegylation, the prolongation technology used for the half-life extension, is a new approach in hemophilia B. Glycopegylation has been shown to be safe and effective in hemophilia A and other therapeutic areas, according to Novo Nordisk.

The paradigm 1 pharmacokinetics (PK) trial (n = 16) was a single-dose escalation study evaluating the safety and PK of nonacog beta pegol compared with that of marketed recombinant and plasma-derived factor IX products. Nonacog beta pegol showed up to a twofold increase in recovery, higher activity levels, and a fivefold prolongation of half-life compared with existing treatments.

The paradigm 2 pivotal trial (n = 74) was a 52-week, single-blind, randomized study evaluating the safety, efficacy, and PK of nonacog beta pegol in adults and adolescents for routine prophylaxis and for the treatment of bleeds. When provided at 40 IU/kg weekly, nonacog beta pegol showed a median annualized spontaneous bleeding rate of 0.0. Further, 97% of breakthrough bleeds were treated successfully, and 90% of target joints were no longer classified as such.

The paradigm 3 surgery trial (n = 13) was a dedicated study confirming the safety and efficacy of nonacog beta pegol during and after major surgical procedures. In all of the patients, a single preoperative dose provided effective hemostatic coverage, and no patient required additional doses on the day of surgery. In addition, three doses of nonacog beta pegol proved sufficient in maintaining hemostasis during the first two weeks after the procedure.

The paradigm 4 extension trial (n = 71) involved patients previously treated in the paradigm 2 and paradigm 3 studies. This safety extension trial with longer-term exposure to nonacog beta pegol demonstrated a well-tolerated safety profile. The investigators identified no inhibitors or other safety signals.

The paradigm 5 pediatric trial (n = 25) was a 52-week single-arm study evaluating once-weekly prophylaxis and treatment of bleeding episodes with nonacog beta pegol in previously treated children 1 to 12 years of age. Nonacog beta pegol appeared to be safe in this cohort. All of the patients maintained mean factor-activity levels above 15% one week after a 40-IU/kg dose. Median ABRs were 0.0 and 2.0 for children up to 6 years of age and 7 to 12 years of age, respectively.

Source: Novo Nordisk (link is external); May 16, 2016.

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