CLINICAL TRIALS PROFILE FOR KRYSTEXXA

All Clinical Trials for KRYSTEXXA

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT01739660 ↗	Study to Assess Pegloticase (KRYSTEXXA®) in Patients on Hemodialysis	Completed	Savient Pharmaceuticals	Phase 1	2012-12-01	This is a Phase 1 single dose study conducted to evaluate the PK and PD of pegloticase administered to hemodialysis patients. A single dose of pegloticase will be administered intravenously to male or female hemodialysis patients (N = 12) starting 3 hour prior to dialysis. The study consists of a Screening Period, a Treatment Period, and Follow up Period.
NCT02598596 ↗	Tolerization Reduces Intolerance to Pegloticase and Prolongs the Urate Lowering Effect	Completed	IND 2 Results LLC	Phase 2	2015-12-01	The purpose of this study is to evaluate the effect of a high zone tolerizing regimen of pegloticase on clinical outcome, as defined by an serum uric acid level <6 mg/dL, in patients with chronic, refractory gout.
NCT02598596 ↗	Tolerization Reduces Intolerance to Pegloticase and Prolongs the Urate Lowering Effect	Completed	Ampel BioSolutions, LLC	Phase 2	2015-12-01	The purpose of this study is to evaluate the effect of a high zone tolerizing regimen of pegloticase on clinical outcome, as defined by an serum uric acid level <6 mg/dL, in patients with chronic, refractory gout.
NCT03303989 ↗	REduCing Immunogenicity to PegloticasE (RECIPE) Study	Completed	University of Michigan	Phase 2	2018-06-14	Pegloticase treatment for chronic refractory gout is limited by immunogenicity. The investigators propose the REduCing Immunogenicity to PegloticasE (RECIPE) trial to begin to investigate the question of whether a short course of immune modulating therapy with mycophenolate mofetil can significantly and safely attenuate immunogenicity to pegloticase and ensure patients afflicted with chronic refractory gout have better treatment outcomes and improved quality of life.
NCT03303989 ↗	REduCing Immunogenicity to PegloticasE (RECIPE) Study	Completed	University of Alabama at Birmingham	Phase 2	2018-06-14	Pegloticase treatment for chronic refractory gout is limited by immunogenicity. The investigators propose the REduCing Immunogenicity to PegloticasE (RECIPE) trial to begin to investigate the question of whether a short course of immune modulating therapy with mycophenolate mofetil can significantly and safely attenuate immunogenicity to pegloticase and ensure patients afflicted with chronic refractory gout have better treatment outcomes and improved quality of life.
NCT03899883 ↗	Uric Acid Lowering Trial in Youth Onset T2D	Recruiting	University of Colorado Denver School of Medicine Barbara Davis Center	Phase 2	2020-01-01	Adolescents and young adults with youth-onset type 2 diabetes (T2D) are disproportionally impacted by hyperuricemia compared to non-diabetic peers and youth with type 1 diabetes (T1D). In fact, 50% of males with youth-onset T2D have serum uric acid (SUA) greater than 6.8 mg/dl. The investigators also recently demonstrated that higher SUA conferred greater odds of developing hypertension and diabetic kidney disease (DKD) in youth with T2D over 7 years follow-up. Elevated SUA is thought to lead to cardiovascular disease (CVD) and DKD by inflammation, mitochondrial dysfunction and deleterious effects on nephron mass. While there are studies demonstrating beneficial effects of uric acid (UA) lowering on vascular health in the general population, there are no studies in youth-onset T2D. Youth-onset T2D carries a greater risk of DKD and CVD compared to adult-onset T2D and T1D. Accordingly, a clinical trial evaluating UA lowering therapies is needed in youth-onset T2D. Krystexxa (pegloticase), a uricase, effectively lowers SUA and therefore holds promise as a novel therapy to impede the development of CVD and DKD in youth-onset T2D. This proposal describes a pilot and feasibility trial evaluating the effect of UA lowering by pegloticase on markers of CVD and DKD in ten (n=10) youth aged 18-25 with youth-onset T2D (diagnosed <21 years of age) over 7 days. The overarching hypothesis is that pegloticase improves marker of cardiorenal health by lowering UA.
NCT03905512 ↗	A Study to Compare the Efficacy of SEL-212 to KRYSTEXXA® in Gout Patients Refractory to Conventional Therapy	Completed	Selecta Biosciences, Inc.	Phase 2	2019-03-28	This is a randomized, parallel-arm, multicenter study to compare the safety and efficacy profiles of SEL-212 and KRYSTEXXA®. Patients will be randomized 1:1 to receive treatment with SEL-212 or KRYSTEXXA® for 6 months. Efficacy assessments, as measured by serum uric acid (SUA) levels, will be conducted at intervals that are appropriate to determine treatment effect differences. Safety will be monitored throughout the study.

Clinical Trial Conditions for KRYSTEXXA

Condition Name

Condition Name for KRYSTEXXA
Intervention	Trials
Chronic Gout	2
Gout	2
Hematopoietic and Lymphoid Cell Neoplasm	1
Hyperuricemia	1

Condition MeSH

Condition MeSH for KRYSTEXXA
Intervention	Trials
Gout	3
Kidney Diseases	2
Diabetic Nephropathies	1
Diabetes Mellitus, Type 2	1

Clinical Trial Locations for KRYSTEXXA

Trials by Country

Trials by Country for KRYSTEXXA
Location	Trials
United States	59

Trials by US State

Trials by US State for KRYSTEXXA
Location	Trials
Texas	4
Pennsylvania	4
Maryland	4
Alabama	4
North Carolina	3

Clinical Trial Progress for KRYSTEXXA

Clinical Trial Phase

Clinical Trial Phase for KRYSTEXXA
Clinical Trial Phase	Trials
Phase 4	3
Phase 2	4
Phase 1	1

Clinical Trial Status

Clinical Trial Status for KRYSTEXXA
Clinical Trial Phase	Trials
Completed	6
Not yet recruiting	1
Recruiting	1

Clinical Trial Sponsors for KRYSTEXXA

Sponsor Name

Sponsor Name for KRYSTEXXA
Sponsor	Trials
Savient Pharmaceuticals	1
IND 2 Results LLC	1
Ampel BioSolutions, LLC	1

Sponsor Type

Sponsor Type for KRYSTEXXA
Sponsor	Trials
Industry	6
Other	4

KRYSTEXXA Market Analysis and Financial Projection

KRYSTEXXA: Clinical Trials, Market Analysis, and Projections

Introduction to KRYSTEXXA

KRYSTEXXA, also known as pegloticase, is a recombinant uricase enzyme approved by the FDA for the treatment of chronic refractory gout (CRG) in adult patients. It is the first and only biologic treatment for this condition, which is characterized by high urate levels and symptoms that are not adequately controlled by conventional therapies[5].

Clinical Trials Update

MIRROR Randomized Controlled Trial

The MIRROR trial was a pivotal study that evaluated the efficacy and safety of KRYSTEXXA when co-administered with methotrexate. This trial involved 152 adults randomized to receive either KRYSTEXXA with methotrexate or KRYSTEXXA with a placebo for 52 weeks. The results showed a significant decrease in blood pressure and a reduction in infusion reactions in the group receiving KRYSTEXXA with methotrexate compared to the placebo group. Patients without pre-treatment chronic kidney disease (CKD) showed a more pronounced decrease in blood pressure[1].

AGILE Trial

The AGILE trial assessed the safety, tolerability, and efficacy of KRYSTEXXA administered with a shorter infusion duration of 60 minutes, compared to the standard 120-minute infusion. The trial found that 67.2% of participants achieved and maintained a urate level of < 6mg/dL for at least 80% of the time during Month 6. Additionally, the incidence of infusion reactions was similar to the MIRROR trial, with 6.0% of participants experiencing an infusion reaction, including anaphylaxis in 1.7% of participants[4][5].

Market Analysis

Market Dominance and Pricing

KRYSTEXXA holds a monopolistic position in the market for CRG treatment, as it is the only FDA-approved medication for this condition. This market dominance has allowed Horizon Therapeutics (now part of Amgen) to charge a high price for the drug, with an annual wholesale acquisition cost of approximately $650,000. This is significantly higher than other gout medications, such as colchicine, which has a much lower retail cost[2].

Sales Projections

Despite the high cost, KRYSTEXXA has seen strong sales performance. Horizon Therapeutics increased its U.S. peak annual net sales expectations for KRYSTEXXA to greater than $1.5 billion, driven by the successful launch of the expanded label that includes co-administration with methotrexate. This expansion has led to increased clinical conviction among physicians and a higher adoption rate, with over 60% of new patient starts using KRYSTEXXA with immunomodulation[3].

Market Competition and Future Outlook

Emerging Competition

While KRYSTEXXA currently enjoys a monopoly in the CRG market, there is anticipation of increasing competition from clinical-stage rivals. Companies like Selecta Biosciences are developing potential competitors, which could capture substantial market share if they successfully enter the market. This emerging competition is expected to benefit patients, doctors, and healthcare payers by potentially reducing prices and improving treatment options[2].

International Market Opportunities

In addition to the U.S. market, there is significant potential for KRYSTEXXA in international markets. Horizon Therapeutics has increased its ex-U.S. peak annual net sales expectations for other products like TEPEZZA, indicating a broader global strategy that could also benefit KRYSTEXXA[3].

Health and Economic Benefits

Systemic Connections and Comorbidities

KRYSTEXXA's effectiveness extends beyond just treating gout symptoms. It has been shown to reduce blood pressure and potentially offer health benefits for patients with comorbid conditions like CKD. A validated microsimulation model projected that effective serum urate reduction with KRYSTEXXA could prevent 300,000 cases of uncontrolled gout by 2035 in the CKD population[1].

Economic Impact

The high cost of KRYSTEXXA is a significant factor in its economic impact. However, the drug's ability to prevent complications associated with uncontrolled gout, such as kidney damage and frequent hospitalizations, can lead to long-term cost savings. The prevention of 300,000 cases of uncontrolled gout, as projected, would have substantial economic benefits for healthcare systems and patients[1].

Safety and Efficacy

Common Adverse Reactions

KRYSTEXXA is associated with several common adverse reactions, including gout flares, infusion reactions, nausea, contusion or ecchymosis, and nasopharyngitis. The AGILE trial and other studies have shown that the incidence of infusion reactions can be managed with co-administration of methotrexate and shorter infusion durations[5].

Infusion Reactions

Infusion reactions are a significant concern with KRYSTEXXA. However, the co-administration of methotrexate has been shown to reduce the incidence of these reactions. The AGILE trial demonstrated that a shorter infusion duration of 60 minutes did not increase the risk of infusion reactions compared to the standard 120-minute infusion[4].

Regulatory and Label Updates

Expanded Label

In 2022, the FDA approved the supplemental Biologics License Application (sBLA) to expand the KRYSTEXXA label to include co-administration with methotrexate. This update was based on the positive results from the MIRROR randomized controlled trial, which showed significant improvements in response rate and sustained patient response, as well as a reduction in infusion reactions[3].

Conclusion

KRYSTEXXA remains a critical treatment option for adults with chronic refractory gout, offering significant clinical benefits despite its high cost. Ongoing clinical trials, such as the AGILE trial, continue to support its efficacy and safety profile. As the market evolves with potential new competitors, the future outlook for KRYSTEXXA will depend on its ability to maintain market share and demonstrate continued value to patients and healthcare systems.

Key Takeaways

• Clinical Efficacy: KRYSTEXXA has shown significant efficacy in reducing urate levels and improving symptoms in patients with CRG.
• Market Dominance: KRYSTEXXA holds a monopolistic position in the CRG market, allowing for high pricing.
• Sales Projections: Peak annual net sales expectations for KRYSTEXXA have been increased to greater than $1.5 billion.
• Emerging Competition: Potential competitors could enter the market, impacting KRYSTEXXA's market share.
• Health and Economic Benefits: KRYSTEXXA offers systemic health benefits and potential long-term cost savings.
• Safety Profile: Common adverse reactions include gout flares and infusion reactions, which can be managed with co-administration of methotrexate.

FAQs

What is KRYSTEXXA used for?

KRYSTEXXA is used for the treatment of chronic refractory gout (CRG) in adult patients who have failed to normalize serum uric acid and whose signs and symptoms are inadequately controlled with conventional therapies[5].

How does KRYSTEXXA work?

KRYSTEXXA is a recombinant uricase enzyme that converts urate into a water-soluble liquid, allantoin, which can be easily excreted from the body[3].

What are the common adverse reactions associated with KRYSTEXXA?

Common adverse reactions include gout flares, infusion reactions, nausea, contusion or ecchymosis, and nasopharyngitis[5].

Can KRYSTEXXA be administered with other medications?

Yes, KRYSTEXXA can be co-administered with methotrexate, which has been shown to reduce infusion reactions and improve efficacy[3].

What is the current market outlook for KRYSTEXXA?

KRYSTEXXA is expected to continue its strong sales performance, with peak annual net sales expectations increased to greater than $1.5 billion. However, emerging competition could impact its market share in the future[3].

Sources

1. AMGEN PRESENTS NEW DATA THAT SHOW BLOOD PRESSURE DECREASES FOR ADULTS TREATED WITH KRYSTEXXA (pegloticase) - Amgen Newsroom[1].
2. Amgen Horizon Part III Complaint PUBLIC - FTC[2].
3. Horizon Therapeutics plc Reports Third-Quarter 2022 Financial Results, Increases Full-Year 2022 Net Sales and Adjusted EBITDA Guidance - Business Wire[3].
4. AMGEN PRESENTS NEW DATA ACROSS RARE INFLAMMATORY DISEASES AT ACR 2024 - Amgen Investors[4].
5. AMGEN PRESENTS NEW DATA ACROSS RARE INFLAMMATORY DISEASES AT ACR 2024 - PR Newswire[5].