When does the patent for Burosumab-twza expire?

Overview of Burosumab-twza

Burosumab-twza is a human monoclonal antibody that targets fibroblast growth factor 23 (FGF23), a hormone implicated in phosphate metabolism. Excess FGF23 lowers phosphate levels by reducing renal reabsorption and impairing the synthesis of active vitamin D, thereby leading to skeletal abnormalities and rickets or osteomalacia. Burosumab-twza—commercially known as CRYSVITA®—is indicated for the treatment of X-linked hypophosphatemia (XLH) in both pediatric and adult populations, as well as for certain cases of tumor-induced osteomalacia (TIO) where excessive FGF23 is a key factor in disease pathology. Its mechanism of action, which involves neutralizing FGF23 activity, helps restore phosphate homeostasis and improve bone mineralization. This targeted therapeutic profile has elevated burosumab-twza as a critical therapy for rare metabolic bone disorders, contributing to both improved patient outcomes and a unique positioning within the biopharmaceutical market.

Manufacturer and Market Presence 
Burosumab-twza is the result of a collaboration between Kyowa Hakko Kirin Co., Ltd. and Ultragenyx Pharmaceutical Inc. The product has received regulatory approval in both the European Union and the United States, reflecting its robust clinical efficacy and safety profiles. With approvals dating back to April 2018 in the US and conditional marketing authorization granted by the EMA for pediatric use, burosumab-twza plays a significant role in addressing unmet needs within the XLH patient community. Its launch has also paved the way for continued expansion into related indications such as tumor-induced osteomalacia, thereby solidifying its commercial presence and establishing a unique market niche among biologic therapies for rare diseases.

Patent Information

Patent Details 
The protection of burosumab-twza is underpinned by a broad and layered portfolio of patents covering various aspects of the molecule, including its composition of matter, methods of manufacturing, and methods of use. Given the complexity of biologics, the intellectual property strategy often includes multiple patents that collectively secure market exclusivity for a significant period. In the case of burosumab-twza, while a single “master” patent may not encapsulate all protection, a series of related U.S. patents (and corresponding international patents) provide patent term protection that spans more than one decade. The patent portfolio is managed carefully to cover both the therapeutic molecule and its clinical applications, ensuring that competitors face significant hurdles before launching biosimilar or generic versions. This multi-faceted approach also takes into account regulatory exclusivity provisions and orphan drug designations that further extend the protection afforded to the innovator product.

Expiration Date 
Based on available information from structured regulatory filings and annual reports, particularly from the Ultragenyx Pharmaceutical Inc. 2022 Annual Report, the U.S. patents covering Crysvita® (burosumab-twza) are set to expire between 2028 and 2035. 
- Some key patents in the portfolio are scheduled to expire in the earlier part of this range, around 2028, which likely relate to earlier-filed compositions of matter or core therapeutic claims. 
- Other patents, possibly covering secondary formulations, manufacturing processes, or additional use cases, may extend exclusivity until as late as 2035. 

In addition to these composition and method patents, burosumab-twza benefits from regulatory exclusivity provisions. For instance, CRYSVITA is protected in the U.S. not just by patents but also by regulatory exclusivity until 2030. Furthermore, orphan drug exclusivities add additional layers of market protection, lasting until 2025 for XLH and until 2027 for TIO, respectively. These layers of exclusivity and patent protection, when taken together, create a robust barrier against immediate competition from generics or biosimilars for a considerable period, even as individual patents may expire on a staggered schedule.

Implications of Patent Expiration

Impact on Market Competition 
When patent protection expires, significant changes occur in the competitive landscape. The expiration of one or more patents for burosumab-twza can significantly impact market dynamics in several ways: 
- Price Erosion and Market Penetration of Generics/Biosimilars: With the expiration of patents between 2028 and 2035, generic and biosimilar manufacturers may enter the market. This typically results in rapid price reductions and an erosion of market share for the innovator product as competitive pricing strategies force down prices. 
- Strategic Moves by the Innovator: Anticipating the challenges posed by patent expiration, companies like Ultragenyx and Kyowa Hakko Kirin may adopt strategic measures such as lifecycle management through new formulations, additional indications, or combination therapies to preserve market share even as key patents expire. 
- Market Exclusivity Gaps: It is important to note that although certain patents expire by the earlier date (e.g., 2028), overlapping patents and regulatory exclusivities (until 2030 or beyond) can delay the immediate impact on competition. This staggered expiration schedules allow the original developer to maintain competitive pricing and market leadership while preparing for generic entry. 
- Expansion of Biosimilar Development: The expiration timeline provides a clear signal for generic manufacturers to begin the process of developing biosimilar candidates. However, given the complexity of biologics like burosumab-twza, the entry of biosimilars is subject to regulatory guidelines and rigorous comparability exercises, which may prolong the timeline for effective market entry despite the patent expiration.

Generic Drug Development 
From a drug development perspective, the expiration of burosumab-twza patents opens the door for biosimilar development. This process is both scientifically complex and highly regulated: 
- Scientific Challenges: Biosimilars must demonstrate that they are highly similar to the reference product with no clinically meaningful differences in terms of safety, purity, and potency. For a biologic as complex as burosumab-twza, this necessitates advanced analytical techniques, robust clinical trials, and more extensive manufacturing controls compared to small-molecule drugs. 
- Regulatory Pathways: Generic manufacturers must navigate what is known as the “patent dance” in the United States, a series of steps required by regulatory bodies such as the FDA to ensure that all patent issues are resolved before market entry. Although the process is streamlined compared to earlier practices, it remains rigorous. The regulatory pathway for biosimilars includes demonstrating bioequivalence along with additional clinical data in some cases, which may delay the entry of competitors even after patent expiration. 
- Market Penetration Dynamics: Once approved, biosimilars can quickly gain significant market share, especially in markets that have a history of robust generic penetration. For burosumab-twza, however, the unique nature of the patient population and the orphan status in some indications might lead to a more gradual uptake despite patent expiry. Moreover, the innovator may still enjoy a substantial lead time due to established relationships with healthcare providers and patients, along with brand loyalty fostered through years of clinical performance.

Regulatory and Market Considerations

Regulatory Pathways for Generics 
The transition from patent-protected status to a market with competing biosimilars is governed by strict regulatory frameworks: 
- Data Exclusivity and Orphan Drug Designations: In addition to patent protection, burosumab-twza enjoys regulatory exclusivity benefits. The U.S. regulatory system allows for data exclusivity periods during which generic manufacturers cannot rely on the innovator’s data for approval. For burosumab-twza, this regulatory data exclusivity extends until 2030, which helps to delay biosimilar entry even if individual patents expire earlier. 
- Biosimilar Approval Pathways: For a biosimilar candidate to obtain approval post-patent expiry, it must satisfy comprehensive regulatory criteria that establish similarity in pharmacokinetics, pharmacodynamics, efficacy, safety, and immunogenicity compared to burosumab-twza. These requirements are underpinned by rigorous analytical studies, clinical trials, and post-marketing surveillance strategies. 
- Patent Dance Procedures: In the United States, innovators and biosimilar developers engage in what is colloquially known as the “patent dance,” which is a structured process of information exchange and potential litigation aimed at clarifying the intellectual property landscape. This process can influence the timing and strategic launch of biosimilar products even after the expiration of key patents.

Market Dynamics Post-Patent Expiration 
The eventual expiration of the patents governing burosumab-twza is expected to set off a cascade of market dynamics that will shape both pricing and competitive behavior: 
- Price Competition: Once the major patents expire, generic manufacturers are likely to introduce biosimilars that offer the same biochemical profiles as burosumab-twza but at significantly lower prices. Historical analyses across various drug classes have consistently demonstrated rapid price reductions post-patent expiry, with original innovator products often experiencing declines that stabilize only after a period of competitive adjustment. 
- Shift in Market Share: As generic or biosimilar versions enter the market, the original product’s market share may decline substantially. However, this process can vary depending on the strength of the supporting clinical data, the robustness of the brand’s market presence, and the innovator’s supplementary strategies such as new indications or reformulations. 
- Strategic Industry Responses: Innovator companies may respond to impending patent cliffs by emphasizing innovation through the extension of product lifecycles. This includes seeking additional patents for new formulations or indications, leveraging real-world data to support extended claims, or engaging in strategic collaborations that can maintain market dominance despite generic competition. 
- Long-Term Market Sustainability: In the long term, while the introduction of biosimilars is beneficial for cost-cutting and increased access, the original innovator’s focus may shift to newer therapies in the pipeline. Thus, the expiration timeline serves both as an opportunity for biosimilar entrants and as a critical juncture for the innovator to reallocate resources toward next-generation therapeutics.

Conclusion

In summary, the patent portfolio for burosumab-twza, also marketed as CRYSVITA®, features multiple U.S. patents that are structured to expire between 2028 and 2035. While individual patents in the portfolio offer varying periods of protection—with some key patents expiring as early as 2028 and others extending protection until 2035—the overall market exclusivity is further enhanced by regulatory data exclusivity (extending until 2030) and orphan drug exclusivity (lasting until 2025 for XLH and 2027 for TIO). This robust protection mechanism not only secures the innovator’s market position for a considerable period but also provides a well-defined timeline for when biosimilar and generic entrants might emerge.

From a market perspective, the expiration of these patents will likely result in significant price competition and a shift in market share as biosimilar manufacturers enter the fray, albeit with the challenges inherent in replicating a complex biologic. Regulatory pathways, including the biosimilar approval process and the “patent dance,” will further shape the pace and impact of this transition. Innovator companies, anticipating these changes, are likely to implement strategic lifecycle management practices to bridge the gap until they transition to their next generation of products.

Ultimately, the expiration of the patents for burosumab-twza marks a critical milestone not only for the product’s lifecycle management but also for the broader dynamics of competition and innovation in the biopharmaceutical industry. Companies must prepare to navigate the ensuing market and regulatory challenges while leveraging new opportunities to sustain their competitive edge.

For an experience with the large-scale biopharmaceutical model Hiro-LS, please click here for a quick and free trial of its features！