Factoring in Factor X

FDA approves Coagadex® for rare bleeding disorder
Author: Sarah M. Aldridge, MS

Factor X (FX) deficiency is not the rarest of the rare bleeding disorders, but it’s rare enough. With a worldwide incidence of 1 in 500,000 to 1 in 1 million and only 400–600 patients in the US, the incentive to develop and market a FX concentrate has been lacking. That is, until now. In October, the US Food and Drug Administration (FDA) announced that it had approved Coagadex®, a plasma-derived FX concentrate for hereditary FX deficiency, from Bio Products Laboratory, Ltd (BPL). BPL is a UK-based manufacturer of plasma-derived products, with US headquarters in Durham, North Carolina. Coagadex is the first FX concentrate available. It is approved for on-demand treatment and control of bleeds, and for peri­operative management of bleeding.

FX facts

FX was first diagnosed in the 1950s in two people: Rufus Stuart in the US and Audrey Prower in England. Hence, its alternate name: ­Stuart-Prower ­deficiency. FX deficiency is inherited in an autosomal recessive fashion, meaning both parents must have the genetic mutation for their child to have the disorder. Because FX levels are low in all newborns, FX deficiency cannot be confirmed until after a baby is 6 months old.

FX is an enzyme that needs ­vitamin K to help form clots. During the clotting cascade, the process that leads to clot formation in a wound, FX activates prothrombin, another enzyme, converting it to its active form, thrombin, which is needed to form a clot. Patients with FX ­deficiency are considered mild, moderate or severe if their FX levels are 6%–10%, 1%–5% or <1% of normal, respectively.

Symptoms of FX deficiency are similar to factor VIII and IX deficiencies. They include easy bruising, nose and gum bleeds, and joint bleeds. Women may experience menorrhagia (heavy menstrual periods), first-trimester­ miscarriages and postpartum hemorrhage. Patients with mild FX deficiency can have excessive bleeding after trauma or surgery. Those with severe FX deficiency can sustain serious and life-threatening bleeds, such as intracranial hemorrhage and gastrointestinal bleeds.

Inadequate treatment

Until recently, the standard treatment for FX deficiency has been fresh frozen plasma (FFP). “Unfortunately, that can only be administered in the hospital,” says Deborah L. Brown, MD, hematologist at the Gulf States Hemophilia and Thrombophilia Treatment Center in Houston, Texas. Besides, the process is slow, taking up to several hours, making routine prophylaxis impractical and inconvenient for most patients. “The level of FX that you can achieve with a plasma infusion is not that great,” she adds.

Further, FFP contains other clotting factors as well. “You do get factors that you don’t really need,” Brown says. But they’re in a so-called “physiologic concentration,” similar to levels in your body. “So the appropriate balance is there.” Side effects of FFP include fever, allergic reactions and, in rare cases, lung damage, she says.

A newer alternative is prothrombin complex concentrates (PCCs), which come in small vials. The advantage of PCCs over FFP is that they can be administered at home. “It’s a simple IV push over a few minutes, as opposed to an infusion, which takes hours,” Brown says. The viral inactivation method for PCCs usually includes a solvent detergent step. “The track record for safety is very, very good,” says Brown.

But PCCs have their downside. Although manufacturers provide information on the amount of FX in PCCs, each vial is not specifically labeled. “You don’t have accurate dosing information,” Brown says. In addition, most PCCs contain four vitamin K-dependent clotting factors: FII, FVII, FIX and FX. “There’s not a balance,” says Brown. Patients must prevent FX levels from exceeding 50%. “There have been rare instances of clots developing after getting PCCs,” Brown cautions.

Coagadex clinical trials

Results from BPL’s phase III clinical trials of Coagadex paved the way for its approval. In a multicenter international study of 16 people with moderate or severe FX deficiency, nearly 83% of bleeds resolved with only one infusion of Coagadex. Further, the product’s half-life was approximately 30 hours.

The data were unveiled at the Hemostasis and Thrombosis Research Society’s Scientific Symposium in New Orleans in April and published online. “It looked like the efficacy was quite good,” Brown says. Nearly 99% of the subjects reported good or excellent results when treating bleeds.

The advantages of having a FX concentrate to treat FX deficiency include better prevention and control of bleeds, with the option of home therapy. Plus, the amount of FX will be indicated on the vial, so patients will know how much they’re using. Being able to store and use FX concentrate at home means bleeds will be treated much more quickly. “This will enable patients to use it prior to procedures, after trauma or injuries, and for prophylaxis,” says Brown.

Having a FX concentrate on the market takes the guesswork out of treatment. “That is highly desirable,” says Brown.