Hemophilia B: Long-Acting Factor IX May Be Big Improvement

Larry Hand

December 05, 2013

A long-acting coagulation factor treatment of patients with hemophilia B is safe and effective for preventing bleeding events, according to an article published online December 4 and in the December 12 issue of the New England Journal of Medicine.

Jerry S. Powell, MD, from the University of California at Davis, and colleagues conducted a nonrandomized, open-label phase 3 trial of the safety, efficacy, and pharmacokinetics of a recombinant factor IX fragment crystallizable (Fc) fusion protein (rFIXFc; Biogen Idec). They enrolled 123 previously treated male patients (aged 12 years and older) with severe hemophilia B.

Factor IX is a protein produced naturally by the body to help blood to clot. Factor IX injections have been associated with improved outcomes for patients with hemophilia B, but the frequency of injections can be a burden. Researchers developed rFIXFc in hopes of prolonging the molecule's half-life and reducing injection frequency.

The researchers divided patients into 4 groups: weekly dose-adjusted 50 IU of rFIXFc per kilogram of body weight to start; interval-adjusted 100 IU per kilogram every 10 days to start; treatment with rFIXFc for bleeding as needed; and treatment with rFIXFc before, during, and after surgery. A subgroup of the first group also underwent comparative pharmacokinetic assessments of rFIXFc and an approved factor IX product (BeneFIX, Pfizer).

Group 1, those who received prophylaxis treatment, experienced an 83% reduction in annualized rate of bleeding compared with those who received treatment per episodes of bleeding (group 3), the researchers determined through binomial regression modeling.

Among the participants who underwent dosing interval adjustments (group 2) and were in the study at least 6 months, 14 participants (53.8%) went 14 or more days between dosing during the last 3 months of the study. In comparison, patients who are now using recombinant factor IX prophylaxis require at least 2 doses a week.

For the total of 636 bleeding episodes that occurred during the study, a single injection resolved 90.4% of bleeding episodes, and 1 or 2 injections resolved 97.3% of episodes.

For 14 patients who underwent surgeries, including knee replacements, investigators or surgeons rated the blood-clotting response during the perioperative period as excellent for 13 and good for 1.

Landscape Changer

"This product is going to essentially remodel the landscape for hemophilia B therapy. For the first time, we have a product with a substantial enough circulating half-life that it will make a major difference in how severe hemophilia B patients treat themselves," Craig M. Kessler, MD, professor of medicine and pathology and director of the Hemophilia and Thrombophilia Treatment Center, Georgetown University, Washington, DC, told Medscape Medical News. Dr. Kessler, who was not involved in the study, is also chair of the medical and scientific advisory committee for the National Hemophilia Foundation.

"Particularly provocative is the ability to develop a treatment regimen that would allow most patients now to be placed on a prophylaxis regimen that would be adequate to prevent bleeds into joints," he continued. "You can essentially change the phenotype of the disease in individuals who have hemophilia B who may bleed 50 times a year. [If they] receive this drug, you bring down the annual breed rate close to zero for most of these patients."

Of 10,000 cases of hemophilia in the United States, hemophilia B accounts for 2000 cases, Dr. Kessler said.

"In this situation, science is moving faster than our ability to absorb what the implications will be [of] having an extended half-life product available for us," he added. "That issue notwithstanding, this is a major accomplishment in the treatment of hemophilia and will probably be also so significant that it will replace the urgency to get gene therapy available for hemophilia B."

The treatment may not be necessary for all patients, he noted. "I think there are many hemophilia B patients who don't need this particular kind of drug. They're doing very well on what they're currently taking as a recombinant factor IX."

What remains unknown is how patient behavior patterns will change when taking the molecule and whether the molecule will have any effect on the immunology of patients, he explained.

A big unknown, he said, is "whether or not the cost in the future is really going to provide a cost–benefit advantage. The acceptance of this product is probably going to be based on price."

"For the bleeding disorders community, particularly those living with severe factor IX deficiency, this could be a significant step forward in treatment and their ability to lead a healthy lifestyle," Val Bias, chief excecutive officer of the National Hemophilia Foundation in New York City, told Medscape Medical News.

"For many people with severe hemophilia, their ability to lead a full professional life and a full family life is limited by their ability to function within the limits of their clotting factor regimen," he continued. "I'm a full-time [chief executive officer], I have a busy schedule, and I have a 5-year-old son. The question is, for me, the dosage that I've set my life at, is it adequate to both do my profession and come home and play with my son."

Bias said if this product is introduced into the highly competitive haemophilia marketplace, it will open the door to further new innovations in the pipeline.

This research was sponsored and funded by Biogen Idec as a prelicensure study. Dr. Powell has reported receiving clinical trial funding from 7 pharmaceutical companies. Twelve coauthors have reported that they are employees and stockholders of Biogen Idec; several coauthors have reported receiving grants and/or fees from one or more pharmaceutical companies, some including Biogen Idec. In addition 1 coauthor has reported being an employee of and holding stock in Biogen Idec at the time of this research; 1 coauthor has reported begin a paid consultant for and stockholder in Biogen Idec; 2 coauthors have disclosed no relevant financial relationships. Dr. Kessler has reported that he has consulted for Biogen Idec. Bias reported not relevant financial interests.

N Engl J Med. 2013;369:2313-2323. Abstract

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