CLINICAL TRIALS PROFILE FOR CRYSVITA

All Clinical Trials for CRYSVITA

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT04146935 ↗	Examining the Effect of Burosumab on Muscle Function	Recruiting	Yale University	Phase 4	2019-11-13	Patients with X-linked hypophosphatemia (XLH) often report symptoms of fatigue and weakness particularly after exertion, in addition to their skeletal complaints. In previous trials using KRN23 (same drug as burosumab/Crysvita®), patients report these symptoms improve. The investigators wish to test this hypothesis directly by measuring muscle energy when patients begin treatment with Crysvita® for the first time.
NCT03993821 ↗	Burosumab for CSHS	Active, not recruiting	Children's National Research Institute	Early Phase 1	2019-07-01	Burosumab (also known as the drug, Crysvita®) is a fully human immunoglobulin G1 (IgG1) monoclonal antibody (mAb) that binds to and inhibits the activity of fibroblast growth factor 23 (FGF23), leading to an increase in serum phosphorus levels. This drug is already approved for use in patients with X-linked hypophosphatemia (XLH), but not for Cutaneous Skeletal Hypophosphatemia Syndrome (CSHS). It is hypothesized that burosumab may provide clinical benefit to a patient with CSHS due to the common underlying feature in this patient and in patients with XLH - abnormally elevated FGF23 in the context of low age -adjusted serum phosphorous levels.
NCT03993821 ↗	Burosumab for CSHS	Active, not recruiting	Children's Research Institute	Early Phase 1	2019-07-01	Burosumab (also known as the drug, Crysvita®) is a fully human immunoglobulin G1 (IgG1) monoclonal antibody (mAb) that binds to and inhibits the activity of fibroblast growth factor 23 (FGF23), leading to an increase in serum phosphorus levels. This drug is already approved for use in patients with X-linked hypophosphatemia (XLH), but not for Cutaneous Skeletal Hypophosphatemia Syndrome (CSHS). It is hypothesized that burosumab may provide clinical benefit to a patient with CSHS due to the common underlying feature in this patient and in patients with XLH - abnormally elevated FGF23 in the context of low age -adjusted serum phosphorous levels.
NCT03993821 ↗	Burosumab for CSHS	Active, not recruiting	Ultragenyx Pharmaceutical Inc	Early Phase 1	2019-07-01	Burosumab (also known as the drug, Crysvita®) is a fully human immunoglobulin G1 (IgG1) monoclonal antibody (mAb) that binds to and inhibits the activity of fibroblast growth factor 23 (FGF23), leading to an increase in serum phosphorus levels. This drug is already approved for use in patients with X-linked hypophosphatemia (XLH), but not for Cutaneous Skeletal Hypophosphatemia Syndrome (CSHS). It is hypothesized that burosumab may provide clinical benefit to a patient with CSHS due to the common underlying feature in this patient and in patients with XLH - abnormally elevated FGF23 in the context of low age -adjusted serum phosphorous levels.
NCT03993821 ↗	Burosumab for CSHS	Active, not recruiting	Laura Tosi	Early Phase 1	2019-07-01	Burosumab (also known as the drug, Crysvita®) is a fully human immunoglobulin G1 (IgG1) monoclonal antibody (mAb) that binds to and inhibits the activity of fibroblast growth factor 23 (FGF23), leading to an increase in serum phosphorus levels. This drug is already approved for use in patients with X-linked hypophosphatemia (XLH), but not for Cutaneous Skeletal Hypophosphatemia Syndrome (CSHS). It is hypothesized that burosumab may provide clinical benefit to a patient with CSHS due to the common underlying feature in this patient and in patients with XLH - abnormally elevated FGF23 in the context of low age -adjusted serum phosphorous levels.
NCT03920072 ↗	Study of the Anti-FGF23 Antibody, Burosumab, in Adults With XLH	Active, not recruiting	Kyowa Kirin Pharmaceutical Development Ltd	Phase 3	2019-03-07	This is phase 3b open-label, international, multicenter study to continue to monitor the long-term safety and efficacy of burosumab in adult patients with XLH that participated in previous clinical trials with burosumab (UX023-CL303 / UX023-CL304).

Clinical Trial Conditions for CRYSVITA

Condition Name

Condition Name for CRYSVITA
Intervention	Trials
X-linked Hypophosphatemia (XLH)	3
X-linked Hypophosphatemia	2
Cutaneous Skeletal Hypophosphatemia Syndrome (CSHS)	1
Epidermal Nevus Syndrome	1

Condition MeSH

Condition MeSH for CRYSVITA
Intervention	Trials
Hypophosphatemia	6
Familial Hypophosphatemic Rickets	5
Osteomalacia	1
Neoplasms, Connective Tissue	1

Clinical Trial Locations for CRYSVITA

Trials by Country

+

−

Trials by Country for CRYSVITA
Location	Trials
China	3
Italy	2
United States	2
France	2
United Kingdom	2

Trials by US State

+

−

Trials by US State for CRYSVITA
Location	Trials
Connecticut	1
District of Columbia	1

Clinical Trial Progress for CRYSVITA

Clinical Trial Phase

Clinical Trial Phase for CRYSVITA
Clinical Trial Phase	Trials
Phase 4	4
Phase 3	1
Phase 1/Phase 2	1

Clinical Trial Status

Clinical Trial Status for CRYSVITA
Clinical Trial Phase	Trials
Recruiting	4
Active, not recruiting	2
Not yet recruiting	1

Clinical Trial Sponsors for CRYSVITA

Sponsor Name

Sponsor Name for CRYSVITA
Sponsor	Trials
Kyowa Kirin Co., Ltd.	3
Kyowa Kirin Pharmaceutical Development Ltd	2
Children's National Research Institute	1

Sponsor Type

Sponsor Type for CRYSVITA
Sponsor	Trials
Industry	6
Other	4

CRYSVITA: Clinical Trials, Market Analysis, and Projections

Introduction

CRYSVITA (burosumab-twza) is a groundbreaking treatment for X-linked hypophosphatemia (XLH), a rare genetic disorder characterized by low phosphate levels in the blood, leading to softening of the bones. Here, we delve into the latest clinical trial updates, market analysis, and projections for this innovative drug.

Clinical Trials Update

Pediatric Trials

A significant Phase 3 clinical study involving 61 patients aged 1 through 12 in several countries, including the U.S., Europe, Canada, Australia, Japan, and Korea, compared the efficacy and safety of CRYSVITA with conventional therapy. The study revealed that CRYSVITA significantly improved mean alkaline phosphatase levels into the normal range after 40 weeks of treatment. Key findings include:

• Primary Endpoint: CRYSVITA showed a substantial healing of rickets, with a least squares mean (LS Mean) change in the radiographic global impression of change (RGI-C) score of +1.92, compared to +0.77 for conventional therapy, resulting in a treatment difference of 1.14 (95% CI: 0.83, 1.45) with a p-value < 0.0001[1].
• Secondary Endpoints: CRYSVITA also demonstrated significant improvements in other rickets assessments, growth velocity, height, walking ability, and patient-reported outcomes such as pain and fatigue[1].

Adult Trials

In adults, CRYSVITA has shown promising results in improving phosphate levels and healing fractures. A study over 24 weeks indicated that more patients treated with CRYSVITA achieved normal phosphorus levels compared to those on placebo. Notably:

• Fracture Healing: Adults continuing CRYSVITA treatment showed healing of 57% of active fractures and 65% of active pseudofractures by week 48. Those switching from placebo to CRYSVITA also showed significant healing rates[4].

Market Analysis

Revenue Growth

CRYSVITA has been a revenue driver for Ultragenyx, with significant growth observed in recent years. In the second quarter of 2024, CRYSVITA revenue reached $114 million, representing a 37% growth compared to the same period in 2023. This includes substantial product sales growth in Latin America and Turkey, with a 140% increase[5].

Market Forecast

The global CRYSVITA market is expected to continue its upward trajectory. Here are some key projections:

• Revenue Projections: Ultragenyx has increased its total revenue guidance to $530 million to $550 million for 2024, with CRYSVITA revenue expected to be towards the upper end of the $375 million to $400 million range[5].
• Regional Dominance: The market is expected to be dominated by regions where Ultragenyx has strong distribution networks, including North America, Europe, and emerging markets in Latin America and Turkey[2].

Competitive Landscape

The rare disease market, particularly for treatments like CRYSVITA, is characterized by limited competition due to the niche nature of the conditions. However, Ultragenyx faces risks related to competition from other therapies or products that may emerge in the future. The company's dependence on Kyowa Kirin for the commercial supply of CRYSVITA also poses potential risks[5].

Market Trends and Drivers

Increasing Awareness

Growing awareness of XLH and the availability of effective treatments like CRYSVITA are driving market growth. Healthcare providers and patients are becoming more aware of the benefits of CRYSVITA, leading to increased adoption.

Regulatory Approvals

The favorable benefit-risk profile of CRYSVITA, as acknowledged by regulatory bodies such as Health Canada, has been crucial in its market authorization. This approval extends to patients 1 year of age and older, including adolescents, based on pharmacokinetic and pharmacodynamic models[3].

Technological Advancements

Advancements in biotechnology and the development of monoclonal antibodies like burosumab-twza have enabled targeted treatments for rare genetic disorders. This technological trend is expected to continue, supporting the growth of the CRYSVITA market.

Challenges and Restraints

Manufacturing Risks

Ultragenyx faces manufacturing risks, including dependence on third-party partners and potential disruptions in supply chains. These risks could impact the availability and consistency of CRYSVITA supply[5].

Market Penetration

Despite strong revenue growth, there are risks related to smaller-than-anticipated market opportunities. The transition of exclusive promotion rights back to Kyowa Kirin in the U.S. and Canada also poses challenges and potential costs[5].

Consumer Behavior and ESG Analysis

Patient Outcomes

Patient-reported outcomes such as reduced pain, fatigue, and improved physical function are critical drivers of consumer behavior. Positive outcomes from CRYSVITA treatment have contributed to its market success[1].

Environmental, Social, and Governance (ESG) Factors

The ESG analysis of the CRYSVITA market highlights the social impact of providing effective treatments for rare diseases. Ultragenyx's commitment to patient access and affordability programs aligns with ESG principles, enhancing the company's reputation and market standing[2].

Regional Analysis

Global Market

The global CRYSVITA market is segmented into various regions, with North America and Europe being key markets due to their established healthcare systems and high awareness of rare diseases. Emerging markets in Latin America and Turkey are also showing significant growth[2].

Country-Level Data

Customized data analysis at the country level reveals varying adoption rates and market sizes. For instance, the strong growth in Latin America and Turkey is driven by expanding healthcare infrastructure and increasing access to rare disease treatments[2].

Conclusion

CRYSVITA has established itself as a leading treatment for X-linked hypophosphatemia, with robust clinical trial data and strong market performance. As the global market continues to grow, driven by increasing awareness, regulatory approvals, and technological advancements, Ultragenyx is well-positioned to capitalize on these trends.

Key Takeaways

• Clinical Success: CRYSVITA has shown significant efficacy in both pediatric and adult populations, improving bone health and reducing symptoms of XLH.
• Market Growth: The drug has seen substantial revenue growth, with projections indicating continued success in the coming years.
• Regulatory Support: Favorable regulatory approvals and a strong benefit-risk profile have been crucial for market authorization.
• Challenges: Manufacturing risks, market penetration challenges, and the transition of promotion rights are key areas to monitor.

FAQs

What is CRYSVITA used for?

CRYSVITA (burosumab-twza) is used to treat X-linked hypophosphatemia (XLH), a rare genetic disorder that leads to low phosphate levels in the blood and softening of the bones.

What are the key findings from the Phase 3 clinical trial in pediatric patients?

The Phase 3 trial showed that CRYSVITA significantly improved mean alkaline phosphatase levels, healed rickets, and improved growth velocity, height, and patient-reported outcomes compared to conventional therapy[1].

How has CRYSVITA performed in terms of revenue growth?

In the second quarter of 2024, CRYSVITA revenue reached $114 million, representing a 37% growth compared to the same period in 2023, with significant growth in Latin America and Turkey[5].

What are the potential risks and challenges for CRYSVITA in the market?

Manufacturing risks, dependence on third-party partners, market penetration challenges, and the transition of exclusive promotion rights back to Kyowa Kirin are key risks and challenges[5].

Which regions are expected to dominate the global CRYSVITA market?

North America, Europe, and emerging markets in Latin America and Turkey are expected to dominate the global CRYSVITA market due to their established healthcare systems and growing demand for rare disease treatments[2].

Sources

1. Ultragenyx and Kyowa Kirin Announce Topline Phase 3 Study Results for Crysvita in Pediatric Patients with X-linked Hypophosphatemia. Ultragenyx.
2. Crysvita Market Report 2024 (Global Edition). Cognitive Market Research.
3. Summary Basis of Decision for Crysvita. Health Canada.
4. Efficacy in Adults | Crysvita® (burosumab-twza). Crysvita.
5. Ultragenyx Reports Second Quarter 2024 Financial Results and Updates Full-Year Guidance. Ultragenyx.