- Analysis of clinical trial efficacy results and estimated factor IX levels suggests that patients who maintain factor IX activity levels above 5 and 10 percent have significantly reduced bleeding risk
- IDELVION is the first and only factor IX therapy with up to 14-day dosing for routine prophylaxis in appropriate hemophilia B patients
Global biotherapeutics leader CSL Behring today announced new results from its Phase III clinical development program evaluating IDELVION® [Coagulation Factor IX (Recombinant), Albumin Fusion Protein], the company’s novel, long-acting recombinant albumin fusion protein for the treatment of hemophilia B. The results, from a pooled analysis of clinical studies from the global PROLONG-9FP program, assessed the relationship between estimated factor IX activity levels and clinical bleeding risk in adult hemophilia B patients treated with IDELVION using prophylaxis or on-demand (episodic) treatment. Analysis of factor IX activity versus efficacy showed that adult patients achieving sustained factor IX activity levels above 5 or 10 percent, have approximately 80 percent lower risk of bleeding events over one year compared with patients having factor IX activity levels below these thresholds. The findings were presented at the 58th annual meeting of the American Society of Hematology (ASH) in San Diego, December 3-6.
“This new analysis of Phase III IDELVION clinical trials shows a strong association between high and prolonged factor IX levels and efficacy of IDELVION in reducing bleeding risk in adult hemophilia B patients,” said John Roberts, Ph.D., Director of Clinical Pharmacology, CSL Behring, and lead investigator. “These findings provide additional clinical rationale for targeting and maintaining factor IX trough activity levels above 5 or 10 percent to optimize treatment outcomes, aligning with World Federation of Hemophilia clinical guidelines for the management of hemophilia.”
In March 2016, IDELVION was approved in the U.S. The long-acting therapy is also approved in the European Union, Japan, Australia, Switzerland and Canada. In the U.S., IDELVION is indicated for use in children and adults with hemophilia B for routine prophylaxis to prevent or reduce the frequency of bleeding episodes, on-demand control and prevention of bleeding episodes and the perioperative management of bleeding (around the time of surgery). Regulatory approvals of IDELVION were based on results from the global PROLONG-9FP clinical development program, which included five Phase I through Phase III open-label, multicenter studies evaluating the pharmacokinetics (PK), safety and efficacy of IDELVION in children and adults with hemophilia B.
“CSL Behring’s research presentation at ASH 2016 demonstrates our commitment to advance coagulation science and optimize treatment outcomes for people living with hemophilia B,” said Jerry Powell, M.D., Medical Director, North America Commercial Operations, CSL Behring. “IDELVION is the only available recombinant factor IX therapy that maintains high factor levels using 14-day dosing intervals, helping to provide excellent bleeding control for hemophilia B patients. Furthermore, IDELVION has been shown to maintain high steady-state factor IX levels (21 percent at 7 days and 13 percent at 14 days, on 7- and 14-day dosing regimens, respectively).”
Key Study Findings
Bleeding risk reduction in relation to predicted factor IX levels in hemophilia B patients receiving IDELVION (abstract #1411): This abstract reported on a pharmacostatistical analysis utilizing pooled PK and efficacy data from the pivotal Phase III trials from PROLONG-9FP. A total of 478 bleeding episodes in 57 adult patients with hemophilia B (factor IX levels ≤2 percent) were evaluated. Investigators estimated factor IX activity levels utilizing available PK data and population PK methods for patients receiving IDELVION prophylaxis treatment (7-day, 10-day and 14-day regimens) and on-demand treatment. The majority of bleeding episodes occurred during the on-demand phase of the studies.
The results suggest a statistically significant relationship between factor IX exposure and bleeding risk, as measured by the time from the start of treatment to the first major bleeding event. Patients taking IDELVION for one year who maintained cumulative factor IX trough levels above 5 percent and above 10 percent were predicted to significantly reduce their bleeding risk by greater than 80 percent, compared with patients having lower trough levels of factor IX activity. Sustained cumulative factor IX activity above 2 percent did not provide significant risk reduction over one year. Patients with daily factor IX trough levels above 5 percent and 10 percent were also predicted to reduce their everyday bleeding risk by greater than 77 percent on average.
About Hemophilia B
Hemophilia B is a congenital bleeding disorder characterized by deficient or defective factor IX; nearly all affected patients are male. People with hemophilia B may experience prolonged or spontaneous bleeding, especially into the muscles, joints, or internal organs. According to the U.S. Centers for Disease Control and Prevention, the condition affects approximately one in 25,000 male births.
IDELVION is approved in the United States, European Union, Japan, Australia, Switzerland and Canada. For more information about IDELVION, including full prescribing information, please visit www.IDELVION.com/prescribing-information.
IDELVION Important Safety Information
IDELVION®, Coagulation Factor IX (Recombinant), Albumin Fusion Protein (rFIX-FP), is indicated in children and adults with hemophilia B (congenital factor IX deficiency) for:
- On-demand control and prevention of bleeding episodes
- Perioperative management of bleeding
- Routine prophylaxis to prevent or reduce the frequency of bleeding episodes
IDELVION is not indicated for induction of immune tolerance in patients with hemophilia B.
IDELVION is contraindicated in patients who have had life-threatening hypersensitivity to the product or its components, including hamster proteins.
IDELVION is for intravenous use only. IDELVION can be self-administered or administered by a caregiver with training and approval from a healthcare provider or hemophilia treatment center. Higher dose per kilogram body weight or more frequent dosing may be needed for pediatric patients.
Hypersensitivity reactions, including anaphylaxis, are possible. Advise patients who self-administer to immediately report symptoms of hypersensitivity, including angioedema, chest tightness, hypotension, generalized urticaria, wheezing, and dyspnea. If symptoms occur, discontinue IDELVION and administer appropriate treatment.
Development of neutralizing antibodies (inhibitors) to IDELVION may occur. If expected factor IX activity plasma levels are not attained or bleeding is not controlled with appropriate dose, perform an assay to measure factor IX inhibitor concentration. Factor IX activity assay results may vary with the type of activated partial thromboplastin time reagent used.
Thromboembolism (e.g., pulmonary embolism, venous thrombosis, and arterial thrombosis) can occur when using factor IX-containing products. In addition, nephrotic syndrome has been reported following immune tolerance induction in hemophilia B patients with factor IX inhibitors and allergic reactions to factor IX.
The most common adverse reaction (incidence ≥1%) reported in clinical trials was headache.
About CSL Behring
CSL Behring is a global biotherapeutics leader which is driven by its promise to save lives. Focused on serving patients’ needs by using the latest technologies, we develop and deliver innovative therapies that are used to treat coagulation disorders, primary immune deficiencies, hereditary angioedema, inherited respiratory disease, and neurological disorders. The company's products are also used in cardiac surgery, organ transplantation, burn treatment and to prevent hemolytic disease of the newborn.
CSL Behring operates one of the world's largest plasma collection networks, CSL Plasma. The parent company, CSL Limited (ASX:CSL), headquartered in Melbourne, Australia, employs more than 17,000 people with operations in more than 30 countries. For more information visit www.CSLBehring.com and follow us on www.Twitter.com/CSLBehring.