Hidden veins. Worn-out veins. Blown veins. People with hemophilia who infuse factor products feel the frustration from uncooperative veins.
One solution for overtaxed veins is to create factor products with more staying power in the bloodstream. Biogen Idec is conducting phase 3 clinical trials on longer-lasting factor products. The B-LONG study is for people with severe hemophilia B; A-LONG is for people with severe hemophilia A.
Both studies are testing recombinant factor proteins using Fc fusion technology. The neonatal Fc receptor was discovered in human placenta. It helps carry immunoglobulin G (IgG), an antibody produced by the mother, to the fetus. The Fc receptors are also in endothelial cells that line blood vessels. They bind and recycle IgG, preventing it from being broken down in the body and accounting for its longer half-life in the blood.
This natural recycling mechanism is the basis for Biogen Idec’s rFVIIIFc and rFIXFc products. “By fusing the back-end portion of an immunoglobulin molecule onto another protein, like FIX or FVIII, one may increase the half-life of those proteins by using this recycling mechanism,” says Glenn Pierce, MD, PhD, senior vice president and chief medical officer of Biogen Idec’s hemophilia therapeutic area in Waltham, Massachusetts.
Patients in the trials are divided into four groups: low-dose prophylaxis, high-dose prophylaxis, on-demand (treating once a bleed has begun) or surgery. They must be at least 12 years old and have had a minimum of 150 infusions without antibody, or inhibitor, development. “This allows us to evaluate if new drugs being tested are responsible for an inhibitor,” says Pierce.
Results of the phase 1/2 study for rFIXFc look promising. Compared with existing FIX products, which have an average half-life of 18 hours, Biogen Idec’s product nearly tripled that time. “That may translate into the possibility of weekly, or even less frequent, infusions for patients with hemophilia B,” Pierce says.
“Because FVIII has a more intricate breakdown process and doesn’t last as long in the plasma, rFVIIIFc won’t show the same increase as rFIXFc, but may significantly prolong the existing dosing regimen,” says Pierce. Results of the phase 1/2 study will be presented at the XXIII Congress of the International Society on Thrombosis and Haemostasis meeting in Kyoto, Japan, July 23–28, 2011.
If longer-lasting factor products are approved by the US Food and Drug Administration following a thorough evaluation of safety, not only will veins get a break, but so will patients. “These products may allow patients to have greater control over their disease,” Pierce says.