CRYSVITA Drug Profile

Summary for Tradename: CRYSVITA

High Confidence Patents:	0
Applicants:	1
BLAs:	1
Recent Clinical Trials:	See clinical trials for CRYSVITA

Recent Clinical Trials for CRYSVITA

Identify potential brand extensions & biosimilar entrants

Sponsor	Phase
Kyowa Kirin Co., Ltd.	Phase 4
Kyowa Kirin Pharmaceutical Development Ltd	Phase 1/Phase 2
Yale University	Phase 4

See all CRYSVITA clinical trials

Note on Biologic Patents

Matching patents to biologic drugs is far more complicated than for small-molecule drugs.

DrugPatentWatch employs three methods to identify biologic patents:

1. Brand-side disclosures in response to biosimilar applications

These patents were identified from disclosures by the brand-side company, in response to a potential biosimilar seeking to launch. They have a high certainty of blocking biosimilar entry. The expiration dates listed are not estimates — they're expiration dates as indicated by the brand-side company.

2. DrugPatentWatch analysis and company disclosures

These patents were identified from searching various sources, including drug labels and other general disclosures from the brand-side company. This list may exclude some of the patents which block biosimilar launch, and some of these patents listed may not actually block biosimilar launch. The expiration dates listed for these patents are estimates, based on the grant date of the patent.

3. Patents from broad patent text search

For completeness, these patents were identified by searching the patent literature for mentions of the branded or ingredient name of the drug. Some of these patents protect the original drug, whereas others may protect follow-on inventions or even inventions casually mentioning the drug. The expiration dates listed for these patents are estimates, based on the grant date of the patent.

1) High Certainty: US Patents for CRYSVITA Derived from Brand-Side Litigation

No patents found based on brand-side litigation

2) High Certainty: US Patents for CRYSVITA Derived from DrugPatentWatch Analysis and Company Disclosures

No patents found based on company disclosures

3) Low Certainty: US Patents for CRYSVITA Derived from Patent Text Search

No patents found based on company disclosures

CRYSVITA Market Dynamics, Revenue Trajectory, Exclusivity, and Competitive Risk

Last updated: September 7, 2026

CRYSVITA, or burosumab-twza, is a commercially established biologic for FGF23-mediated phosphate-wasting disorders. Its market has expanded through pediatric and adult XLH treatment, tumor-induced osteomalacia, and additional rare-disease indications. Ultragenyx Pharmaceutical and Kyowa Kirin commercialize the product under a global collaboration.

CRYSVITA’s principal advantages are disease-specific mechanism, chronic-use positioning, limited direct biologic competition, and expansion into adults with X-linked hypophosphatemia. Its main risks are high treatment cost, payer controls, diagnosis rates, injection burden, safety monitoring, and eventual biosimilar competition after biologic exclusivity expires.

What is CRYSVITA and how does it work?

CRYSVITA is a recombinant human IgG1 monoclonal antibody that binds and inhibits fibroblast growth factor 23, or FGF23. Excess FGF23 reduces renal phosphate reabsorption and suppresses active vitamin D production. Burosumab restores phosphate handling and improves mineralization in affected patients.

Attribute	CRYSVITA
Active ingredient	Burosumab-twza
Drug class	Anti-FGF23 monoclonal antibody
Originators	Ultragenyx Pharmaceutical and Kyowa Kirin
FDA approval	April 17, 2018
Initial indication	Pediatric patients age 1 year and older with XLH
Adult XLH approval	2020
Tumor-induced osteomalacia	FDA approval in 2020
Administration	Subcutaneous injection, generally every two to four weeks depending on indication and patient age
Regulatory category	Biologic license application product
Primary commercial markets	United States, Japan, Europe and selected international markets

The product treats the underlying phosphate-wasting pathway rather than supplying phosphate and active vitamin D alone. Conventional treatment remains an alternative for some patients, particularly where access, reimbursement, or clinical suitability limits burosumab use.

What diseases does CRYSVITA treat?

X-linked hypophosphatemia

XLH is an inherited phosphate-wasting disorder caused primarily by pathogenic variants affecting the PHEX pathway. The resulting FGF23 excess can cause rickets, bone deformities, short stature, dental disease, pain, fractures, enthesopathy and impaired mobility.

The commercial XLH opportunity includes:

• Children diagnosed through genetic testing or characteristic skeletal findings.
• Adolescents transitioning into adult care.
• Adults with persistent skeletal and dental complications.
• Patients previously treated with phosphate and active vitamin D.
• Family members identified through cascade testing.

The adult opportunity materially increased CRYSVITA’s addressable population. Adult patients may have longstanding disability and treatment needs even after growth has ended.

Tumor-induced osteomalacia

Tumor-induced osteomalacia, or TIO, is usually caused by a small mesenchymal tumor that secretes FGF23. Surgical removal can be curative when the tumor is located and resectable. CRYSVITA is relevant for patients with unresectable tumors, occult tumors, recurrent disease, or persistent phosphate wasting.

TIO expands the product beyond inherited disease but remains a smaller and more diagnostically difficult market than XLH.

Autosomal dominant hypophosphatemic rickets

In 2023, the FDA expanded the CRYSVITA label to include adults and children age one year and older with tumor-induced osteomalacia, while regulatory activity has also focused on other FGF23-mediated disorders. Autosomal dominant hypophosphatemic rickets, or ADHR, has been an important development area because it is biologically aligned with burosumab’s mechanism, although commercial labeling must be assessed separately by jurisdiction and approval date.

How has CRYSVITA revenue developed?

CRYSVITA has become one of Ultragenyx’s core products. Company disclosures show sustained growth driven by increased diagnosis, adult XLH adoption, international commercialization and broader physician familiarity.

Public reporting can differ because Ultragenyx reports North American product revenue while Kyowa Kirin reports sales in its territories. The figures below represent rounded Ultragenyx-reported CRYSVITA revenue as disclosed in company filings and earnings materials, rather than a consolidated worldwide market-sales figure.

Fiscal year	Approximate Ultragenyx-reported CRYSVITA revenue	Main growth drivers
2020	Approximately $250 million	Pediatric uptake, adult XLH launch, TIO approval
2021	Approximately $350 million	Adult prescribing and broader reimbursement
2022	Approximately $480 million	Continued XLH penetration and international growth
2023	Approximately $590 million	Larger treated population and increased adult use

CRYSVITA represented more than half of Ultragenyx’s product revenue in 2023 on a company-reported basis. The product therefore carries significant concentration risk for Ultragenyx, although the company has attempted to diversify through therapies including EVKEEZA, DOJOLVI and pipeline programs.

Kyowa Kirin’s global sales are not directly additive to Ultragenyx’s reported revenue. The collaboration structure divides territories and economics, making total CRYSVITA market revenue higher than either company’s individual product disclosure.

What is driving CRYSVITA market growth?

Adult XLH penetration

Pediatric treatment created the initial commercial base. Adult XLH has become the more important expansion vector because adults represent a large underdiagnosed population with chronic symptoms and accumulated skeletal damage.

Adult uptake depends on:

• Recognition of XLH by endocrinologists, nephrologists, rheumatologists and orthopedic specialists.
• Access to genetic or biochemical testing.
• Payer acceptance of long-term treatment.
• Demonstration of functional and quality-of-life benefit.
• Referral of patients from pediatric to adult care.

Diagnostic expansion

Rare-disease diagnosis is a structural market constraint. Patients may be misclassified as having nutritional vitamin D deficiency, nonspecific osteomalacia, orthopedic disease or chronic pain. Greater use of serum phosphate testing, FGF23 assessment, family screening and genetic testing increases the number of eligible patients.

Chronic treatment economics

CRYSVITA is administered chronically, creating recurring revenue rather than a one-time treatment cycle. The recurring model supports predictable sales but exposes the product to treatment discontinuation, payer reauthorization and adherence risks.

Limited direct competition

No approved product has the same commercial profile and FGF23 mechanism in XLH. Conventional oral phosphate and active vitamin D remain the main therapeutic alternatives. They are generally less expensive but require frequent dosing and can cause gastrointestinal, renal and mineral-balance complications.

What is the FDA regulatory status of CRYSVITA?

CRYSVITA was approved under a biologics license application in 2018. The FDA label has expanded from pediatric XLH to adult XLH and TIO.

FDA milestone	Timing
Original approval for pediatric XLH	April 2018
Adult XLH expansion	2020
TIO approval	2020
Subsequent label and age-population expansions	Ongoing through supplemental submissions

The product does not have a conventional small-molecule New Drug Application. It is regulated as a biologic, which affects exclusivity, abbreviated competition and patent-dispute procedures.

What is the Orange Book status of CRYSVITA?

CRYSVITA is not protected through the standard Orange Book framework used for small-molecule drugs. Biologic products are generally associated with the FDA Purple Book rather than Orange Book patent listings.

As a result:

• A generic applicant cannot use the ordinary ANDA pathway.
• There is no conventional Paragraph IV certification process for CRYSVITA.
• A competing product would generally be developed under the Public Health Service Act biosimilar pathway.
• Patent disputes would be handled through the Biologics Price Competition and Innovation Act, including the statutory patent-exchange process where applicable.

This distinction is material. Orange Book searches alone do not provide a complete view of CRYSVITA’s exclusivity or competitive risk.

When does CRYSVITA lose regulatory exclusivity?

CRYSVITA’s reference-product exclusivity is generally tied to its first licensure date of April 17, 2018. Under the U.S. biologics framework, a biosimilar generally cannot be approved for marketing until 12 years after first licensure, subject to statutory interpretation and any applicable exclusivity extensions.

The base 12-year period therefore points to April 2030. Pediatric exclusivity, if granted and applicable to the relevant regulatory rights, can extend certain exclusivity protections by six months. The commercial impact depends on the specific exclusivity determination and competing product timing.

Orphan-drug exclusivity may also apply to particular indications. Orphan exclusivity is indication-specific and does not necessarily block a biosimilar across all uses. It can, however, delay approval or commercialization for the protected indication.

What patents protect CRYSVITA?

CRYSVITA protection is expected to rely on a combination of:

• Composition-of-matter patents covering anti-FGF23 antibodies.
• Antibody sequence and binding-site claims.
• Pharmaceutical composition claims.
• Treatment methods for XLH, TIO and other phosphate-wasting disorders.
• Dosing and administration claims.
• Manufacturing and cell-line technology.
• Formulation and stability claims.

Because CRYSVITA is a biologic, the relevant patent estate is more complex than a single small-molecule patent listed in the Orange Book. Patent scope depends on claim construction, validity, written-description support, enablement and the relationship between the reference antibody and a proposed biosimilar.

The strongest protection generally comes from claims that narrowly cover the therapeutic antibody sequence, binding characteristics or specific manufacturing attributes. Method-of-use claims can remain commercially important but may be easier for a biosimilar applicant to avoid through labeling or prescribing restrictions.

Are there Paragraph IV challenges or biosimilar competitors?

No conventional Paragraph IV challenge applies to CRYSVITA because CRYSVITA is a biologic rather than an Orange Book-listed small molecule.

As of the latest broadly available public information, no biosimilar had reached U.S. commercial launch. A future competitor would likely face:

1. Development and comparability requirements under the FDA biosimilar pathway.
2. Immunogenicity and pharmacokinetic evidence requirements.
3. Manufacturing scale-up and supply reliability hurdles.
4. Patent litigation under the BPCIA.
5. Physician and payer reluctance to switch stable rare-disease patients.
6. Limited market size relative to the cost of developing a biosimilar.

A biosimilar could still pressure net pricing before widespread switching if payers use formulary placement, step edits or contracting leverage.

What patent litigation affects CRYSVITA?

The principal legal risk is prospective rather than an established generic-litigation event. A biosimilar applicant could trigger patent litigation by providing a statutory notice and participating in the BPCIA patent-exchange process.

Potential disputes would likely address:

• Whether the biosimilar falls within antibody sequence or epitope claims.
• Validity of antibody and treatment-method patents.
• Obviousness of using anti-FGF23 therapy in XLH or TIO.
• Written description and enablement.
• Manufacturing-process overlap.
• Patent-term and regulatory-exclusivity timing.

No widely reported settlement agreement with a CRYSVITA biosimilar applicant had established an earlier U.S. entry date as of the latest available public disclosures.

How strong is the CRYSVITA patent and exclusivity estate?

CRYSVITA has a relatively strong near- to medium-term commercial protection profile because regulatory exclusivity extends to approximately 2030 and biosimilar development is technically demanding.

Protection layer	Commercial assessment
Biologic regulatory exclusivity	Strong through the late 2020s, subject to statutory details
Orphan exclusivity	Potentially useful for specific indications, but narrower than product-wide protection
Antibody composition claims	Potentially strong if valid and broad enough to cover competing molecules
Method-of-use claims	Useful but vulnerable to label carve-outs
Formulation claims	Secondary protection; strength depends on claim scope
Manufacturing claims	Potentially important, but difficult to enforce if a competitor uses a distinct process
Biosimilar substitution risk	Limited before the first U.S. biosimilar approval; increasing thereafter

The estate is stronger as a combined regulatory, clinical, manufacturing and patent package than as a single patent barrier.

What licensing deal controls CRYSVITA commercialization?

Ultragenyx and Kyowa Kirin entered a global collaboration covering burosumab development and commercialization. The companies divide geographic rights and share economics under the agreement.

Ultragenyx has been primarily associated with commercialization in North America. Kyowa Kirin has commercial rights in Japan and other territories, with regional arrangements varying by market. The agreement gives both companies commercial participation while reducing the need for each party to independently build a global rare-disease infrastructure.

The collaboration is commercially important because CRYSVITA’s worldwide revenue is split across company reporting systems. Analysts should avoid treating Ultragenyx’s reported CRYSVITA revenue as global product sales.

What generic or biosimilar launch scenarios exist?

Early biosimilar entry

An early launch would require a successful challenge to relevant patents or an agreement allowing entry before the end of the full exclusivity period. This scenario appears less likely than post-2030 entry because the product has substantial regulatory exclusivity and complex biologic manufacturing requirements.

Delayed entry near 2030

A biosimilar could enter after regulatory exclusivity expires but remain subject to patent litigation. The first entrant could receive a meaningful advantage through payer contracting and physician familiarity.

Multiple entrants after 2030

Several competitors could enter after the first biosimilar launch. Price erosion would depend on substitution rules, interchangeability designations, payer concentration, and whether competitors target all indications or selected XLH populations.

Non-biosimilar competitive pressure

The more immediate commercial threats are not generic products. They include improved oral therapies, alternative mineral-metabolism treatments, better diagnosis of disease-specific subgroups and payer restrictions that reduce eligible treatment duration.

How does CRYSVITA compare with conventional XLH therapy?

Factor	CRYSVITA	Oral phosphate plus active vitamin D
Mechanism	FGF23 inhibition	Replaces phosphate and active vitamin D
Administration	Intermittent subcutaneous injection	Frequent oral dosing
Disease specificity	High	Lower
Cost	High biologic cost	Lower drug cost
Monitoring	Phosphate and safety monitoring required	Frequent mineral and renal monitoring
Pediatric use	Established	Established
Adult XLH use	Commercially important	Longstanding alternative
Adherence burden	Injection and clinic coordination	Frequent daily dosing
Competition risk	Biosimilar and payer risk	Low-cost standard-of-care pressure

CRYSVITA’s value proposition is strongest in patients with confirmed FGF23-driven disease, persistent complications, inadequate response or tolerability problems with conventional therapy, and sufficient reimbursement support.

What revenue exposure does CRYSVITA create for Ultragenyx?

CRYSVITA is a major revenue concentration for Ultragenyx. Its growth supports cash generation, commercial infrastructure and investment in rare-disease development. A slowdown in adult XLH enrollment, payer restrictions or safety-driven discontinuations would have a disproportionate impact on company performance.

Key financial sensitivities include:

• New patient starts.
• Continuation rates.
• Net price after rebates and discounts.
• Adult versus pediatric mix.
• International royalty and collaboration revenue.
• TIO and other niche-indication growth.
• Manufacturing capacity.
• Biosimilar timing after 2030.

The product’s recurring revenue profile is favorable, but it is not immune to gross-to-net pressure. As the treated population grows, payers may demand more documentation of biochemical response, functional benefit and treatment persistence.

What is the geographic opportunity for CRYSVITA?

The United States remains the central commercial market because of high rare-disease spending and established specialist networks. Japan is strategically important through Kyowa Kirin’s local infrastructure and rare-disease capabilities. Europe provides a substantial opportunity but faces country-specific health technology assessment, reimbursement and budget controls.

Geographic growth depends on:

• National reimbursement decisions.
• Pediatric and adult label scope.
• Availability of specialist diagnosis.
• Genetic testing capacity.
• Local pricing negotiations.
• Distribution and cold-chain infrastructure.
• National substitution rules for future biosimilars.

Emerging markets have lower near-term penetration because of diagnosis gaps, pricing constraints and limited access to specialty biologics.

Key Takeaways

• CRYSVITA is a leading targeted therapy for FGF23-mediated phosphate-wasting disorders.
• XLH, particularly adult XLH, is the principal commercial driver.
• TIO broadens the market but remains a smaller and harder-to-diagnose indication.
• Ultragenyx-reported CRYSVITA revenue grew from roughly $250 million in 2020 to roughly $590 million in 2023.
• CRYSVITA is a biologic and does not follow the conventional Orange Book or Paragraph IV framework.
• U.S. biologic exclusivity points to an important protection milestone around April 2030.
• Biosimilar entry is technically and legally difficult but represents the principal long-term erosion risk.
• The product’s patent protection includes antibody, method-of-use, formulation and manufacturing claims.
• Ultragenyx has significant revenue concentration in CRYSVITA, while worldwide sales are divided with Kyowa Kirin.
• Payer controls, diagnosis rates, treatment persistence and biosimilar timing will determine the next phase of growth.

FAQs

Is CRYSVITA a biologic or a small-molecule drug?

CRYSVITA is a biologic monoclonal antibody regulated through an FDA biologics license application.

Can a generic version of CRYSVITA be filed under an ANDA?

No. A competing product would generally use the FDA biosimilar pathway under the Public Health Service Act rather than the abbreviated new drug application pathway.

What is the expected U.S. biosimilar risk date for CRYSVITA?

The key regulatory exclusivity milestone is approximately April 2030, based on CRYSVITA’s April 17, 2018 first licensure date. Patent disputes could affect actual launch timing.

Does CRYSVITA have direct competition from another FGF23 antibody?

No directly competing approved FGF23 antibody has established the same commercial position in XLH and TIO as CRYSVITA.

Why is adult XLH important to CRYSVITA sales?

Adult XLH expands treatment beyond the initial pediatric population and includes patients with persistent bone, dental, pain and mobility complications requiring long-term management.

References

1. U.S. Food and Drug Administration. (2018). FDA approves first therapy for X-linked hypophosphatemia, a rare inherited form of rickets.
2. U.S. Food and Drug Administration. (2024). CRYSVITA prescribing information.
3. Ultragenyx Pharmaceutical Inc. (2024). Annual report pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 for the fiscal year ended December 31, 2023.
4. Ultragenyx Pharmaceutical Inc. (2024). Fourth-quarter and full-year 2023 financial results.
5. Kyowa Kirin Co., Ltd. (2024). Integrated report and financial results materials.
6. U.S. Food and Drug Administration. (2024). Purple Book: Database of licensed biological products.
7. U.S. Congress. (2010). Biologics Price Competition and Innovation Act of 2009, Pub. L. No. 111-148, §7002.