AlphaNine SD (human coagulation factor IX) for hemophilia

Last updated March 21, 2024, by Margarida Maia, PhD
Fact-checked by Joana Carvalho, PhD

What is AlphaNine SD for hemophilia?

AlphaNine SD (human coagulation factor IX) is a highly purified, plasma-derived clotting factor IX (FIX) concentrate that’s approved to prevent and control bleeding in people with hemophilia B.

The therapy, which is given via an infusion into the vein, or intravenously, was originally developed by Alpha Therapeutics, which was acquired by Grifols in 2003.

AlphaNine SD is an improved version of AlphaNine that incorporates solvent detergent in the process of viral inactivation during its production, which increases the therapy’s purity and safety.

Therapy snapshot

How does AlphaNine SD work?

Hemophilia B is caused by the lack or dysfunctional FIX, a clotting protein in the bloodstream. Without FIX, the blood cannot clot properly to stop bleeding. As a result, people with hemophilia B may have heavy bleeding episodes that last longer than usual and can be difficult to control.

AlphaNine SD contains a highly purified form of FIX derived from human plasma from donors. As such, it can be used as a replacement therapy to temporarily make up for the faulty or missing FIX, helping to prevent and control bleeding episodes in people with hemophilia B.

Who can take AlphaNine SD?

The U.S. Food and Drug Administration (FDA) approved the original version of AlphaNine in December 1990 for preventing and controlling bleeding in hemophilia B. AlphaNine SD was cleared for the same indication by the FDA in 1996.

Who should not take AlphaNine SD?

AlphaNine SD’s prescribing information lists no contraindications for its use.

The label states, however, that the therapy is not indicated for people with:

• clotting factor II, VII, or X deficiencies
• bleeding caused by coumarin anticoagulants, for example, warfarin
• hemophilia A with inhibitors, or neutralizing antibodies, against clotting factor VIII.

How is AlphaNine SD administered?

AlphaNine SD is given as an infusion directly into the bloodstream at no more than 10 mL per minute to avoid vasomotor reactions, or alterations to the diameter of blood vessels in the body.

The concentrate is supplied in color-coded, single-use vials containing 500 (gray), 1,000 (green), or 1,500 (blue) international units (IU) of FIX. It is packaged with 10 mL of diluent (sterile water) for injection and a Mix2Vial filter transfer set for easy reconstitution. When mixed together, concentrate and diluent create a clear solution that should be infused within three hours.

When used to control acute bleeds, AlphaNine’s dosing and frequency will depend on a patient’s clinical response and bleed severity.

• For minor bleeding episodes, such as cuts or scrapes, bruises, and uncomplicated joint bleeds, FIX levels should be brought to at least 20% to 30% of normal using 20 to 30 IU per kilogram of body weight (IU/kg) twice daily until bleeding stops (usually for one or two days).
• For moderate bleeding episodes, such as nose bleeds, mouth and gum bleeds, or tooth extractions, FIX levels should be brought to at least 25% to 50% of normal using 25 to 50 IU/kg twice daily until healing has been achieved (for two to seven days on average).
• For major bleeding episodes, such as joint and muscle bleeds, FIX levels should be brought to 50% of normal for at least three to five days using 30 to 50 IU/kg twice daily and then maintained at 20% of normal with 20 IU/kg twice daily until healing has been achieved. These bleeds may require up to 10 days of treatment.

When used to control bleeds in a surgical setting, AlphaNine SD should be administered at a dose of 50 to 100 IU/kg twice daily to bring FIX levels to 50% to 100% of normal before surgery. The same dosing should be maintained for up to 10 days after surgery, or until healing has been achieved.

AlphaNine SD in clinical trials

An open-label clinical trial sponsored by Grifols tested the safety and efficacy of AlphaNine SD in 25 adults and adolescents, ages 12 and older, who were previously treated for moderate to severe hemophilia B. The patients received a median of 3.2 infusions of AlphaNine SD per month to prevent and control bleeding. The quality of the treatment response was rated on a scale of excellent, good, moderate, and none.

Over 12 months, 499 bleeding episodes were reported. From these, 443 (89%) were managed with a single infusion and 56 (11%) with two or three. Among a total of 889 infusions, 827 (93%) were rated as excellent or good regarding their response to treatment. This meant bleeding was controlled readily (excellent) or was as severe and lasted as long as expected (good). There were no side effects related to treatment with AlphaNine SD.

Patients who completed the 12-month treatment period were invited to take part in an extension study, also sponsored by Grifols, where the safety and efficacy of AlphaNine SD were compared with BeneFIX (nonacog alfa), a recombinant (man-made) version of FIX marketed by Pfizer. The study also compared their pharmacokinetics, or how they move into, through, and out of the body.

Twenty-two adults and adolescents, ages 15-45, agreed to participate in the study. After a washout period of at least seven days (one week) following a last dose of 65 to 75 IU/kg of AlphaNine SD, they received a single intravenous infusion of 65 to 75 IU/kg of BeneFIX. Results showed the mean in vivo recovery, a measure that reflects how well a replacement therapy may raise FIX levels in the bloodstream, was significantly higher for AlphaNine SD than for BeneFIX (1.3 vs. 1 IU/deciliter per IU/kg). Neither AlphaNine SD nor BeneFIX led to developing inhibitors against FIX.

Use in surgery

A small clinical trial evaluated the safety and efficacy of the original version of AlphaNine at preventing and controlling bleeds occurring during and after minor or major surgical procedures in 13 previously treated patients with hemophilia B. Before surgery, the patients received doses of AlphaNine ranging from 30.1 to 65.0 IU/kg. After surgery, they received doses that ranged from 9.4 to 52.0 IU/kg for up to 23 days. No bleeding episodes were reported and surgical outcomes were deemed excellent.

A subsequent study assessed the outcomes of 20 hemophilia B patients who had 29 major surgical procedures. All received AlphaNine SD before, during, or after surgery. Results showed AlphaNine SD was safe and effective, with patients having relatively minor blood loss during surgery and no bleeding-related complications.

Common side effects of AlphaNine SD

Like other plasma-derived products, AlphaNine SD may cause:

• allergic reactions
• mild chills
• nausea
• stinging at the infusion site.

Transmission of infectious agents

AlphaNine SD is made from human plasma and, while steps are taken to make it safe by clearing out any harmful infectious agents, there is a chance of it carrying infectious agents, such as viruses or prions (misfolded proteins) like those that cause Creutzfeldt-Jakob disease, a brain disease.

A physician should weigh the potential risks and benefits of using AlphaNine SD and discuss them with the patient.

Blood clots

Some patients have had blood clotting (thrombosis), or disseminated intravascular clotting (widespread blood clotting throughout the blood vessels) after using FIX concentrates containing high levels of clotting factors II, VII, and X.

AlphaNine SD contains low levels of these clotting factors, which should reduce the risk of blood clotting problems. However, patients having surgery and those with known liver disease should be closely monitored for signs and symptoms of disseminated intravascular clotting.

Allergic reactions

Allergic reactions, including anaphylaxis, which is a severe, whole-body allergic reaction, may occur with FIX products, including AlphaNine SD. Often, these reactions occur in close association with developing FIX inhibitors.

If symptoms develop, treatment should be stopped. Urgent medical attention may be required, depending on the severity of the reaction. Symptoms of an allergic reaction may include urticaria (hives), angioedema (swelling under the skin), chest tightness, shortness of breath, wheezing, fainting, low blood pressure, and a fast heart rate.

Immune tolerance induction and nephrotic syndrome

Some patients with FIX inhibitors and a history of severe allergic reactions to FIX have had nephrotic syndrome, a type of kidney damage, after using FIX concentrates for immune tolerance induction, a type of treatment to eliminate inhibitors.  The safety and efficacy of AlphaNine SD in immune tolerance induction are not established.

Use in pregnancy

It’s not known if AlphaNine SD is safe to use during pregnancy. No animal reproduction studies have been conducted with AlphaNine SD, so it isn’t known if it can harm a developing fetus or affect female reproductive capacity. AlphaNine SD’s prescribing information states the medication should only be administered to pregnant women if clearly needed.

Hemophilia News Today is strictly a news and information website about the disease. It does not provide medical advice, diagnosis or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.