1. Introduction of Nonacog beta pegol
Nonacog beta pegol is a recombinant coagulation factor IX derivative. It is produced without animal-derived materials and with an attached 40kDa polyethylene glycol (PEG) molecule for peptide activation by site-directed glycosylation. Once activated, the activation molecule with PEG is cleaved to leave the activated factor IX (Factor IXa). Nonacog beta pegol is a recombinant coagulation factor IX, also known as N9-GP, a pegyl-modified formulation of coagulation factor IX for the treatment of hemophilia B caused by a deficiency of coagulation factor IX. Nonacog beta pegol was developed by Novo Nordisk, and obtained EMA marketing authorization on June 6, 2017.
2. Clinical Application and Advantages
The special about nonfactor substitution is its long-acting and extended half-life. Pegylated clotting factor IX can extend its half-life in the body by binding PEG polymers to its molecules to enhance its uptake by the primary clearance organ (liver). This modification can improve the bioavailability of clotting factors without too many side effects. In addition, because nonfactor substitutes have a longer half-life and a smaller drug degradation rate, they can be given to patients in fewer doses, thereby reducing dose frequency and duration of treatment, and increasing their controllability and convenience.
Another important advantage of nonfactor substitution is that it reduces the chance of an immune response. Since many of the molecules on the PEG-coated surface have hydrolytic properties that they would not otherwise have, the production of antigenicity and other immune reactions due to drug use can be reduced. Moreover, because nonfactor substitutes also have a lower ion content, they are less likely to have an immune response than other factor substitutes.
Clinically, Nonacog beta pegol is widely used for the treatment of hemophilia B caused by deficiency of clotting factor IX. Hemophilia B is a genetic disorder that prevents blood from clotting properly due to a lack of clotting factor IX. Patients are prone to internal bleeding, joint pain, swelling, and, in severe cases, death. Alternative therapy is one of the main methods to treat hemophilia B.
In hemophilia B replacement therapy, the mechanism of action of Nonacog beta pegol is to restore normal clotting function by supplementing the missing clotting factor IX in the patient. PEGylation technology enables a durable plasma concentration of Nonacog beta pegol, which can also reduce the frequency and dose of treatment and improve the therapeutic outcome of patients.
Nonacog beta pegol offers advantages over other factor IX replacement therapies in several ways. It can provide a longer half-life and a more controlled dose while reducing pain, inconvenience, and adverse drug reactions caused by frequent injections. In addition to this, it can also reduce the incidence of immunogenicity and immune response in patients, helping to improve treatment compliance and quality of life in patients during treatment.
Although Nonacog beta pegol has many advantages as a nonfactor substitute, there are still some challenges. Its high price can be a financial strain on many patients, and its potential side effects and safety also need to be studied and monitored over the long term due to its novel PEG structure.
It is important to note that the drug is not suitable for all patients with hemophilia B. Some patients may have an allergic reaction to PEG-ionized clotting factor IX, while others may develop an immune response after treatment and become resistant to the next treatment. In addition, the high price of Nonacog beta pegol also makes it unsuitable for all treatment options.
In the treatment of hemophilia B, Nonacog beta pegol is an effective alternative therapy that can play an important role when coagulation factor IX is insufficient. Due to its PEG-specific structure, Nonacog beta pegol has a long half-life and can reduce the risk of immune response to factor substitutes. However, due to the disadvantages of being expensive and not suitable for everyone, the use of non-factor substitutes requires evaluation and selection by doctors based on individual patient conditions.
In summary, Nonacog beta pegol is a novel agent of PEGyl for coagulation factor IX, which is widely used in the treatment of hemophilia B caused by coagulation factor IX deficiency. It has a good curative effect and controllable efficacy, which helps to improve the treatment effect and quality of life of patients. Although it faces some challenges in terms of its high price and safety, Nonacog beta pegol still has broad development prospects and uses.
3. Clinical research progress
Nonacog beta pegol (recombinant coagulation factor IX) has been approved in many countries such as the United States and the European Union and has entered the clinical application stage. For example, the drug has been approved by the European Medicines Agency (EMA) for the treatment of hemophilia B. The U.S. Food and Drug Administration (FDA) approved the use of Nonacog beta pegol (brand name Alprolix) in preventive alternative therapy in December 2017.
In addition, several alternative factors for factor IX deficiency, such as efmoroctocog alfa and Alprolix, have also been approved by the FDA. Another factor IX alternative therapies in development include BAX335 and N9-GP, which enhance their flux and half-life properties through improved drug construction or the use of new gene cloning techniques.
Overall, Nonacog beta pegol and other factor-replacement agents have become an important tool in the treatment of hemophilia B, which has played an important role in reducing pain and improving the quality of life in patients. With the continuous improvement and development of related technologies, more factor substitutes may emerge in the future, bringing new breakthroughs and progress for the treatment of hemophilia B.
References
- P.W. COLLINS, J. MØSS, et al. Population pharmacokinetic modeling for dose setting of nonacog beta pegol (N9‐GP), a glycoPEGylated recombinant factor IX. Journal of Thrombosis and Haemostasis,Volume 10, Issue 11.
- Massimo Franchini, Francesco Frattini, Silvia Crestani, Cinzia Sissa & Carlo Bonfanti (2013) Treatment of hemophilia B: focus on recombinant factor IX, Biologics: Targets and Therapy, 7:, 33-38.
- Carmen E, Inga HS et al.. Favorable pharmacokinetics in hemophilia B for nonacog beta pegol versus recombinant factor IX‐Fc fusion protein: A randomized trial. Research and Practice in Thrombosis and Haemostasis,Volume 3, Issue 2, 2019.
- Sternebring, O, Gabel-Jensen, C, Jacobsen, H, et al. Steady-State Plasma Concentrations of Polyethylene Glycol (PEG) are Reached in Children and Adults During Once-Weekly Prophylactic Treatment with Nonacog Beta Pegol (N9-GP). BioDrugs 33, 673–681 (2019).