How many FDA approved Recombinant coagulation factor are there?

Introduction to Recombinant Coagulation Factors

Definition and Significance
Recombinant coagulation factors are protein therapeutics manufactured using recombinant DNA technology rather than being isolated from human plasma. These molecules are engineered in cell‐based production systems that mimic the natural post‐translational modifications of the native clotting proteins. This approach ensures high purity, enhanced safety by eliminating the risk of blood‐borne pathogens, and improved consistency between batches. Recombinant products have revolutionized the management of bleeding disorders—especially hemophilia A and B—by providing reliable and standardized treatments that improve patient outcomes and quality of life.

Development and Approval Process
The development of recombinant coagulation factors involves rigorous biotechnological and clinical research. The process starts with molecular cloning of the gene encoding the desired coagulation factor, followed by expression in an appropriate host cell line (e.g., Chinese hamster ovary cells, human embryonic kidney cells, or human cell lines). These recombinant proteins are then purified and undergo extensive testing for biological activity, safety, and immunogenicity. Regulatory agencies such as the U.S. Food and Drug Administration (FDA) evaluate both the preclinical data—focusing on pharmacokinetics, pharmacodynamics, and toxicity profiles—and the results of clinical trials. Only after thorough review does an FDA approval get granted, which assures clinicians and patients of the product’s safety, efficacy, and reliability.

FDA Approved Recombinant Coagulation Factors
The central question asks: “How many FDA approved recombinant coagulation factor are there?” Based on our detailed extraction from multiple drug application references that clearly specify FDA_CBER as the approving authority, we can identify a total of nine unique FDA approved recombinant coagulation factors.

List of Approved Products
The following is a detailed list of the nine FDA approved recombinant coagulation factors along with their manufacturer details, approval dates, and therapeutic indications:

1. ADZYNMA
- Manufacturer: Takeda Pharmaceuticals U.S.A., Inc.
- Approval Details: Approved on November 9, 2023, by FDA_CBER.
- Description: This recombinant product is designed for use in managing bleeding episodes, most likely in hemophilia patients, and represents the latest approval from Takeda’s portfolio.

2. ALTUVIIIO
- Manufacturer: Bioverativ, Inc.
- Approval Details: FDA_CBER approved on February 22, 2023.
- Description: This recombinant coagulation factor is indicated for bleed prophylaxis, especially in patients who require enhanced and sustained factor replacement therapy.

3. Jivi
- Manufacturer: Bayer Healthcare LLC
- Approval Details: Approved on August 29, 2018, by FDA_CBER.
- Description: Jivi is an extended half-life recombinant Factor VIII product used in the treatment of hemophilia A. Its improved pharmacokinetic profile allows for less frequent dosing, making it a popular choice for prophylaxis.

4. Sevenfact
- Manufacturer: Laboratoire Français du Fractionnement et des Biotechnologies
- Approval Details: Received FDA_CBER approval on April 1, 2020.
- Description: This recombinant coagulation factor, with a dosing form as a powder requiring reconstitution, is used for controlling bleeding episodes. Its approval marked an important milestone for products derived from advanced biotechnological processes.

5. Andexxa
- Manufacturer: AstraZeneca AB
- Approval Details: Approved on May 3, 2018, by FDA_CBER.
- Description: Andexxa is a recombinant modified human factor designed primarily for the reversal of factor Xa inhibitors. Although its mechanism is different from traditional replacement therapies, it falls under the category of recombinant coagulation factors approved by the FDA.

6. Esperoct
- Manufacturer: Novo Nordisk, Inc.
- Approval Details: FDA_CBER approved with application number 125671_001.
- Description: Esperoct is a recombinant factor product used for the prophylactic treatment of hemophilia A. It is formulated in different strengths and is approved for intravenous administration.

7. Rebinyn
- Manufacturer: Novo Nordisk, Inc.
- Approval Details: Approved on May 31, 2017, by FDA_CBER with application number 125611_001.
- Description: As a recombinant coagulation factor, Rebinyn serves as another option in the replacement therapy portfolio for patients with hemophilia, offering safety and efficacy improvements over previous plasma-derived products.

8. Vonvendi
- Manufacturer: Takeda Pharmaceuticals U.S.A., Inc.
- Approval Details: Received FDA_CBER approval on December 8, 2015, with application number 125577_001.
- Description: Vonvendi is designed specifically for use in bleeding control, and its recombinant design ensures consistent quality and minimizes immunogenic risks.

9. Afstyla
- Manufacturer: CSL Behring Lengnau AG
- Approval Details: Approved on May 25, 2016, by FDA_CBER with application number 125591_001.
- Description: Afstyla is a well-established recombinant product used in the management of hemophilia, notable for reducing the treatment burden through improved stability and longer circulating half-life.

Therapeutic Applications
Each of these FDA approved recombinant coagulation factors plays a pivotal role in the treatment of various bleeding disorders:
- Hemophilia A and B Treatment: Products such as Jivi, Esperoct, Rebinyn, and Afstyla are central to factor replacement therapy in hemophilia A (Factor VIII deficiency) and hemophilia B (Factor IX deficiency) patients. Their extended half-life formulations and consistent bioactivity have increased prophylactic treatment options and improved patient adherence.
- Bleeding Episode Management: ADZYNMA, Sevenfact, and Vonvendi provide additional options specifically tailored to intervene during acute bleeding episodes, thereby reducing the risk of life‐threatening hemorrhages.
- Reversal Agents: Andexxa exemplifies the emerging class of recombinant products designed for the reversal of anticoagulant effects such as those induced by direct factor Xa inhibitors, expanding the therapeutic landscape beyond traditional replacement strategies.

Clinical Impact and Efficacy

Efficacy in Hemophilia Treatment
Recombinant coagulation factors have demonstrated robust efficacy in clinical trials and real‐world settings. They consistently reduce the frequency of spontaneous bleeding episodes and lower the annualized bleeding rates when used prophylactically. For example, extended half-life products such as Jivi enable patients to experience fewer infusions per week while maintaining adequate trough levels for hemostasis. The improvements in pharmacokinetic profiles have translated to superior joint health outcomes, less joint deterioration over time, and overall enhanced quality of life for patients with hemophilia. Clinical studies have compared these recombinant products with plasma‐derived products, frequently showing comparable or superior efficacy in terms of bleed prevention and rapid hemostatic control.

Comparison with Plasma-Derived Products
One key advantage of recombinant coagulation factors is the elimination of risks associated with plasma-derived products, including the potential for transmission of blood-borne pathogens. Although advancements in viral inactivation and donor screening have made plasma‐derived concentrates significantly safer over the past decades, recombinant products offer a higher degree of purity and consistency. Furthermore, plasma-derived products have a more variable pharmacokinetic profile, potentially leading to less predictable therapeutic outcomes. The recombinant products’ engineered structures allow for modifications—such as pegylation or fusion with albumin/Fc fragments—that extend their half-life and reduce dosing frequency, an important factor when balancing treatment efficacy with patient compliance.

Regulatory and Market Considerations

FDA Approval Criteria
The FDA’s approval process for recombinant coagulation factors is comprehensive. It involves a detailed evaluation of preclinical study data, pharmacokinetic/pharmacodynamic profiles, clinical trial outcomes, immunogenicity testing, and overall product safety. The FDA_CBER (Center for Biologics Evaluation and Research) plays a crucial role in ensuring that each recombinant product meets the stringent criteria required for market authorization. The approval criteria often include demonstration of non-inferiority or superiority in efficacy relative to existing therapies, coupled with a demonstrable decrease in adverse immune reactions compared to plasma-derived products. Such rigorous evaluation ensures that only those recombinant products that offer significant clinical benefits with an acceptable safety profile are approved.

Market Dynamics and Availability
The recombinant coagulation factors market is highly competitive and dynamic. With increasing awareness and diagnosis rates for bleeding disorders, the demand for safe and effective treatments remains robust. Market dynamics are influenced by factors such as:
- Product Differentiation: Companies invest in bioengineering strategies to extend the half-life and reduce dosing frequency, thus differentiating their products in an increasingly crowded market.
- Pricing and Cost-Effectiveness: Although recombinant coagulation factors typically come with a higher production cost than plasma-derived products, this cost is frequently justified by their improved safety profile and clinical efficacy. Payers and healthcare systems weigh the long-term benefits of reduced bleeding rates and hospital admissions against the higher unit price.
- Regulatory Incentives: Given the unmet medical needs in rare bleeding disorders, regulatory agencies sometimes grant accelerated approvals or orphan drug status which further stimulates innovation in this field.
- Global Availability: While the FDA approvals are specific to the United States, many of these products are also approved or under review in regions such as Europe and Japan. This global availability broadens the market and fosters further research and development into next-generation recombinant therapies.

Future Directions and Research

Ongoing Research and Developments
The current pipeline for recombinant coagulation factors continues to evolve rapidly. Research efforts are focused on enhancing the efficacy, prolonging the half-life, and reducing the immunogenicity of these products. For instance, next-generation products are being designed using advanced bioengineering techniques such as:
- Pegylation: Covalent attachment of polyethylene glycol (PEG) to prolong the circulatory half-life by reducing renal clearance and proteolytic degradation.
- Fusion Protein Technologies: Incorporation of Fc or albumin domains to leverage the neonatal Fc receptor recycling pathway, thereby extending the half-life substantially.
- Single-Chain Molecules: Novel single-chain recombinant factors are in development to optimize intrinsic stability and improve binding to cofactors such as von Willebrand factor (VWF), which further stabilizes circulating factor levels.

Ongoing clinical trials continue to evaluate these advanced recombinant molecules not only for their prophylactic efficacy but also in the context of breakthrough bleeding episodes and surgical settings. Their ability to maintain stable factor levels over longer intervals is a primary focus of these trials.

Emerging Therapies and Innovations
Looking toward the future, several innovative therapeutic strategies are emerging that may complement or even replace current recombinant factor treatments. These include:
- Gene Therapy: Approaches to deliver functional copies of the deficient gene into patient tissues, potentially providing a cure rather than regular prophylactic treatments.
- Non-Factor Therapies: Agents that rebalance the coagulation cascade without directly replacing the missing clotting factor. Examples include bispecific antibodies that mimic the function of Factor VIII or modulate natural anticoagulant pathways such as tissue factor pathway inhibitor (TFPI).
- RNA Interference Therapies: These are designed to suppress natural inhibitors of coagulation (such as antithrombin) to enhance the body’s endogenous ability to generate thrombin.

These emerging modalities represent an exciting expansion of the therapeutic arsenal available for managing bleeding disorders. However, while promising, they are in various stages of clinical development and further research is required to assess their long-term safety and efficacy compared to established recombinant products.

Detailed Conclusion
In summary, based on the synthesis of multiple reliable references primarily from the synapse source—as evidenced by the FDA_CBER drug application records—the current count of FDA approved recombinant coagulation factors is nine. These include:
1. ADZYNMA (Takeda Pharmaceuticals U.S.A., Inc.)
2. ALTUVIIIO (Bioverativ, Inc.)
3. Jivi (Bayer Healthcare LLC)
4. Sevenfact (Laboratoire Français du Fractionnement et des Biotechnologies)
5. Andexxa (AstraZeneca AB)
6. Esperoct (Novo Nordisk, Inc.)
7. Rebinyn (Novo Nordisk, Inc.)
8. Vonvendi (Takeda Pharmaceuticals U.S.A., Inc.)
9. Afstyla (CSL Behring Lengnau AG)

From a general perspective, recombinant coagulation factors have vastly improved hemophilia treatment by providing safer, consistent, and more effective therapeutic options compared to plasma-derived alternatives. Specific improvements include extended dosing intervals, lower immunogenicity, and enhanced clinical outcomes, all of which contribute to a better quality of life for patients.

On a specific level, each of the nine products has unique characteristics—from the extended half-life design of Jivi and the engineered reversal capabilities of Andexxa to the innovative formulations like ADZYNMA and ALTUVIIIO—which allow personalized treatment regimens tailored to the patients’ needs. The clinical data demonstrate that these recombinant products have achieved significant success in reducing bleeding rates and minimizing infusion frequency, and their FDA approval underscores their safety and effectiveness.

Finally, from a general and forward-looking standpoint, the development and approval of these nine recombinant coagulation factors highlight the dynamic nature of the biopharmaceutical market. The regulatory process has evolved to support innovative therapies, and ongoing research continues to push the boundaries of treatment—which may ultimately lead to curative strategies such as gene therapy and novel non-factor treatments. The market dynamics and rigorous FDA approval criteria ensure that only products with proven efficacy and safety become available to patients, fostering high-quality standards in hematology therapeutics.

In conclusion, there are nine FDA approved recombinant coagulation factor products as identified from the referenced drug application records. This count reflects the culmination of decades of biotechnological innovation, rigorous clinical research, and strict regulatory oversight. These products have not only transformed the treatment landscape for bleeding disorders but also paved the way for future improvements and emerging therapies that promise to further enhance patient care.