An X-linked recessive disorder, Hemophilia occurs predominantly in males with females being the carriers. Patients diagnosed with Hemophilia usually lack one of the two proteins essential for the blood coagulation cascade namely factor VIII (FVIII) and factor IX (FIX). On the basis of the different blood coagulation factors that are lacking, Hemophilia can be divided into different subtypes namely Hemophilia A and Hemophilia B. In the case of Hemophilia A and factor IX (FIX) in the case of Hemophilia B. While Hemophilia A is a more prevalent form of Hemophilia affecting 1 in 5,000 male births, Hemophilia B is a rare subtype affecting approximately 1 in 25,000 male births.
Hemophilia B can result in excessive bleeding in joints, head, and sometimes brain, which can lead to paralysis, seizures, and even death in severe cases. However, there is no cure for Hemophilia B. The two major approaches opted for Hemophilia B treatment are either preventive or on-demand therapies. However, the best way to target the disease is to replace the missing blood clotting factor known as Replacement therapy. The basic idea of the therapy is to infuse clotting factors through a vein. This can help stop the bleeding, and patients can learn to perform such infusions (prophylaxis) on a regular basis. This can be done with the help of Plasma-Derived Factor IX Concentrates, Fresh Frozen Plasma, and Recombinant Factor IX Therapy. While there is the availability of plasma-derived factors, an inclination towards recombinant therapies is witnessed as recombinant products are potentially a safer alternative that lowers down the risk of blood-borne transmission of infectious diseases. BeneFIX, Rixubis, Ixinity, Alprolix, Idelvion, and Rebinyn are some of the available recombinant factor IX products in the US.
Without a doubt, there are several safe and effective replacement therapies available for patients living with Hemophilia B; however, patients continue to experience bleeding, progressive joint diseases, and degraded quality of life. Further, the development of inhibitors in the patients complicates the treatment and management of Hemophilia B adding to the health burden as well as a financial burden.
Thus, DelveInsight estimates that the futuristic approaches that are expected to dominate the Hemophilia B treatment market would include extended half-life therapies, novel approaches that include siRNA, bispecific antibodies, and gene therapy.
Key pharmaceutical companies such as ApcinteX, Novo Nordisk, Sanofi, Pfizer, Sangamo Therapeutics, Catalyst Biosciences, uniQure, Alnylam, CSL Behring, Freeline Therapeutics, and several others, are dynamically working in developing novel treatment approaches in the Hemophilia B treatment market. Pipeline therapies including SPK 9001 (Pfizer/Spark Therapeutics), AMT-061 (CSL Behring/ uniQure), AMT-060 (UniQure Biopharma B.V.), FLT180a (Freeline Therapeutics), Concizumab (Novo Nordisk), Fitusiran (Sanofi/Alnylam Pharmaceuticals), Marstacimab (Pfizer), Marzeptacog alfa (Catalyst Biosciences), and others shall enter the Hemophilia B market and lead to a significant increase in the market size during the forecast period [2021–2030].
Marstacimab (PF-06741086), a human monoclonal immunoglobulin G isotype, subclass 1 (IgG1) that targets the Kunitz 2 domain of tissue factor pathway inhibitor (TFPI), is a therapeutic candidate in the Hemophilia B treatment market as a prophylactic treatment aimed to prevent or reduce the frequency of bleeding episodes. Pfizer is investigating the agent in Phase III (NCT03938792) clinical trial for the treatment of Severe Hemophilia A and B with or without Inhibitors. Concizumab is also a high-affinity monoclonal antibody against Tissue Factor Pathway Inhibitor (TFPI) intended for bleeding prevention subcutaneous administration under evaluation by Novo Nordisk. At the moment, it is in a Phase III clinical trial for Hemophilia A and B with and without Inhibitors.
Gene therapies provide a long-term benefit to patients by enabling the expression of missing or abnormal coagulation factors for a longer duration at sufficient levels. They are a single-dose treatment approach that can potentially prove to be a cure for Hemophilia B. Etranacogene Dezaparvovec (AMT-061), is under development by UniQure Pharmaceuticals, which comprises an AAV5 viral vector carrying a gene cassette with a Padua variant of Factor IX. The therapy is in Phase III (NCT03569891) clinical trial stage and is expected to complete in August 2024. However, things went downhill following a clinical hold that was put on the company by the USFDA owing to a serious adverse event that took place in the diagnosed case with hepatocellular carcinoma (HCC), a form of liver cancer. UniQure plans to submit the additional data for the safety of the therapy by the end of the first quarter of 2021 to the USFDA.
Another gene therapy, Fidanacogene elaparvovec (previously SPK-9001 or PF-06838435) is a novel, investigational bio-engineered AAV vector under Phase III (NCT03861273) stage of clinical development by Pfizer/Spark Therapeutics. Then there is FLT180a, experimental next-generation gene therapy for hemophilia B that Freeline is evaluating for the Phase I/II (NCT03641703) trial.
Further in the Hemophilia B pipeline, Sanofi (Genzyme)/ Alnylam Pharmaceuticals is developing Fitusiran, a subcutaneously administered small interfering RNA (siRNA) technology to target antithrombin. The drug is in the global phase III ATLAS clinical program for the treatment of hemophilia A and B patients with and without inhibitors.
It is clear that at present the Hemophilia B treatment hemisphere primarily revolves around non-inhibitors drug candidates, which is anticipated to soon be dominated by emerging potential therapies. Several pharma goliaths are exploring to provide a curative option to Hemophilia B patients rather than repetitive infusions of clotting factors. Further, what attracts pharmaceutical companies more is the rare status of the disease. Being an orphan indication, the therapies have an exclusive option to win orphan drug designation, market exclusivity, and other benefits that come under the Orphan drug act. However, with the advent of gene therapies, the cost burden would simply fall straight on the patients. Therefore, better reimbursement policies and affordable healthcare insurance to accommodate these therapies shall help patients uptake of novel Hemophilia B therapies. Nevertheless, the market landscape shall continue to dynamically evolve with the emergence of novel therapies, advanced medical technologies, and better awareness of bleeding disorders.