CLINICAL TRIALS PROFILE FOR NATPARA

All Clinical Trials for NATPARA

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT02781844 ↗	Study to Assess the Blood Concentrations and Actions of Recombinant Human Parathyroid Hormone (rhPTH [1-84]) When Given Once and Twice Daily to Participants With Hypoparathyroidism	Completed	Shire	Phase 1	2017-04-03	This study is being conducted to characterize the effects of twice daily administration of rhPTH(1-84) on the way the body handles rhPTH(1-84) as well as its actions and safety and tolerability over the course of 24 hours as compared with the current once daily dosing regimen of marketed rhPTH(1-84) (marketed in the United States as Natpara® and in the EU as Natpar).
NCT02986607 ↗	Corticosteroid Rhythms in Hypoparathyroid Patients	Unknown status	Haukeland University Hospital	Early Phase 1	2016-03-01	The investigators hypothesise that parathyroid hormon (PTH) depletion interferes with normal activity of the hypothalamus-pituitary-adrenal (HPA)-axis and the renin-angiotensin-aldosterone-system (RAAS), which in turn may impact morbidity and quality of life. The main objective of the current study is to test if PTH deficiency influences the secretion of corticosteroids and whether any abnormalities in the HPA-axis and the RAAS-system can be reversed by PTH infusion.
NCT02986607 ↗	Corticosteroid Rhythms in Hypoparathyroid Patients	Unknown status	University of Bergen	Early Phase 1	2016-03-01	The investigators hypothesise that parathyroid hormon (PTH) depletion interferes with normal activity of the hypothalamus-pituitary-adrenal (HPA)-axis and the renin-angiotensin-aldosterone-system (RAAS), which in turn may impact morbidity and quality of life. The main objective of the current study is to test if PTH deficiency influences the secretion of corticosteroids and whether any abnormalities in the HPA-axis and the RAAS-system can be reversed by PTH infusion.
NCT00473265 ↗	Bone Properties in Hypoparathyroidism: Effects of PTH	Completed	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)	Phase 2/Phase 3	2004-05-01	Whereas much information is known about the properties of bone in primary hyperparathyroidism, a disorder of parathyroid hormone (PTH) excess, virtually nothing is known about the skeleton in hypoparathyroidism, a disorder in which PTH is absent. The purpose of this research project is to test the hypothesis that the skeleton in hypoparathyroidism is abnormal in its metabolic, densitometric, geometric, biomechanical and microarchitectural features. We will also test the hypothesis that the skeleton is dependent upon PTH for normal structure and function. Using non-invasive approaches as well as direct analysis of bone itself, the human hypoparathyroid skeleton will be thoroughly characterized. With each patient serving as his/her own control, we will determine how, to what extent, and in what ways the administration of PTH restores skeletal dynamics and structure to the hypoparathyroid skeleton. In this way, we will identify those structural and dynamic elements of the skeleton that are influenced by or dependent upon PTH. Methods to be utilized include dual energy X-ray absorptiometry, quantitative central and peripheral computed tomography, geometry and size quantification, histomorphometry by standard and microCT methods, finite element analysis, biochemical bone markers, quantitative back scattered electron imaging, and Fourier Transform Infrared Spectroscopy. This research project will extend our knowledge of the skeletal effects of PTH to its deficient range and thus complete our understanding of PTH action on bone gained by our many years of studying PTH overexpression in primary hyperparathyroidism. This investigation may also provide insight into the means by which PTH helps to restore the skeleton when it is used to treat osteoporosis.
NCT00473265 ↗	Bone Properties in Hypoparathyroidism: Effects of PTH	Completed	John P. Bilezikian	Phase 2/Phase 3	2004-05-01	Whereas much information is known about the properties of bone in primary hyperparathyroidism, a disorder of parathyroid hormone (PTH) excess, virtually nothing is known about the skeleton in hypoparathyroidism, a disorder in which PTH is absent. The purpose of this research project is to test the hypothesis that the skeleton in hypoparathyroidism is abnormal in its metabolic, densitometric, geometric, biomechanical and microarchitectural features. We will also test the hypothesis that the skeleton is dependent upon PTH for normal structure and function. Using non-invasive approaches as well as direct analysis of bone itself, the human hypoparathyroid skeleton will be thoroughly characterized. With each patient serving as his/her own control, we will determine how, to what extent, and in what ways the administration of PTH restores skeletal dynamics and structure to the hypoparathyroid skeleton. In this way, we will identify those structural and dynamic elements of the skeleton that are influenced by or dependent upon PTH. Methods to be utilized include dual energy X-ray absorptiometry, quantitative central and peripheral computed tomography, geometry and size quantification, histomorphometry by standard and microCT methods, finite element analysis, biochemical bone markers, quantitative back scattered electron imaging, and Fourier Transform Infrared Spectroscopy. This research project will extend our knowledge of the skeletal effects of PTH to its deficient range and thus complete our understanding of PTH action on bone gained by our many years of studying PTH overexpression in primary hyperparathyroidism. This investigation may also provide insight into the means by which PTH helps to restore the skeleton when it is used to treat osteoporosis.

Clinical Trial Conditions for NATPARA

Condition Name

Condition Name for NATPARA
Intervention	Trials
Hypoparathyroidism	4
Hyperparathyroidism	1

Condition MeSH

Condition MeSH for NATPARA
Intervention	Trials
Hypoparathyroidism	4
Hyperparathyroidism	1

Clinical Trial Locations for NATPARA

Trials by Country

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−

Trials by Country for NATPARA
Location	Trials
United States	11
Hungary	2
Israel	1
Canada	1
Norway	1

Trials by US State

+

−

Trials by US State for NATPARA
Location	Trials
New York	2
Tennessee	1
Pennsylvania	1
Ohio	1
Minnesota	1

Clinical Trial Progress for NATPARA

Clinical Trial Phase

Clinical Trial Phase for NATPARA
Clinical Trial Phase	Trials
Phase 2/Phase 3	1
Phase 2	1
Phase 1	1

Clinical Trial Status

Clinical Trial Status for NATPARA
Clinical Trial Phase	Trials
Completed	3
Unknown status	1

Clinical Trial Sponsors for NATPARA

Sponsor Name

Sponsor Name for NATPARA
Sponsor	Trials
John P. Bilezikian	1
Shire	1
Haukeland University Hospital	1

Sponsor Type

Sponsor Type for NATPARA
Sponsor	Trials
Other	3
Industry	2
NIH	1

NATPARA: Clinical Trials, Market Analysis, and Projections

Introduction to NATPARA

NATPARA, also known as parathyroid hormone (PTH), is a bioengineered replica of the human parathyroid hormone used to treat hypoparathyroidism, a rare endocrine condition characterized by low levels of parathyroid hormone, leading to low blood calcium levels and related health issues.

Clinical Trials Overview

Study Design and Participants

The FDA approved NATPARA based on a 24-week, randomized, double-blind, placebo-controlled trial involving 124 adults with chronic hypoparathyroidism. The study was conducted in multiple centers across North America, Europe, and other regions. Patients were randomized in a 2:1 ratio to receive either NATPARA (n=84) or placebo (n=40)[1][4].

Efficacy Endpoints

The primary efficacy endpoint required patients to meet three criteria:

• A reduction of at least 50% in oral calcium intake from baseline.
• A reduction of at least 50% in active vitamin D dose from baseline.
• Maintenance of a normalized albumin-corrected total serum calcium level between 7.5 and 10.6 mg/dL.

At the end of the treatment, 54.8% of patients on NATPARA achieved the efficacy endpoint, compared to 2.5% on placebo (p < 0.001). Additionally, 42% of NATPARA patients were able to eliminate active vitamin D and reduce oral calcium to 500 mg or less per day, versus 3% of placebo patients[1][4].

Manufacturing and Supply Issues

Takeda, the current manufacturer of NATPARA, has faced significant production challenges, including contamination of rubber particles from the drug’s injector cartridge and other manufacturing issues. Despite efforts to resolve these problems, Takeda has announced that it will stop manufacturing NATPARA by the end of 2024 due to the lack of a sustainable solution[2].

Market Analysis

Current Market Size and Growth

The hypoparathyroidism treatment market, which includes NATPARA, was valued at $1.25 billion in 2023 and is projected to grow at a CAGR of 6.8% to reach $2.25 billion by 2032. North America dominated the market in 2021, with a market share of 39.5%, driven by the rise in thyroid-related disorders and pharmaceutical companies' efforts to develop novel formulations[5].

Product Type and Route of Administration

NATPARA is a key player in the parathyroid hormone segment of the market. However, the market is also driven by other products such as vitamin D analogues and calcium supplements. The parenteral route of administration, which includes injectables like NATPARA, is significant, but oral medications remain the standard treatment for hypoparathyroidism due to their ease of use and lower cost[5].

Regional Analysis

The market is segmented into regions including North America, Europe, Asia-Pacific, the Middle East & Africa, and Latin America. Asia-Pacific is expected to grow at a faster CAGR due to increased government initiatives, awareness, and technological advancements in treatment[5].

Challenges and Restraints

Side Effects and Safety Concerns

NATPARA is associated with several side effects, including a potential risk of osteosarcoma, high blood calcium levels, and reduced sense of touch or pain sensation in joints. These side effects, along with the need for long-term efficacy and safety data, have limited the adoption of NATPARA. The drug is available only through a Risk Evaluation and Mitigation Strategy (REMS) program due to these risks[3].

High Cost and Limited Availability

The high cost of NATPARA and its limited availability due to manufacturing issues have further restricted its market penetration. Patients who abruptly stop taking NATPARA can suffer from serious complications such as severe pain, kidney damage, and cardiac events, making the discontinuation of the drug particularly problematic[2][3].

Future Projections and Impact

Market Growth Drivers

Despite the challenges, the hypoparathyroidism treatment market is expected to grow driven by increased thoracic surgery and cancer incidence, investments in R&D, and government support for new drug development. The development of biologics and novel formulations is anticipated to drive market growth[3][5].

Impact of Manufacturing Discontinuation

The discontinuation of NATPARA production by Takeda will leave a significant gap in the treatment options for patients with hypoparathyroidism who cannot control their blood calcium levels with calcium and vitamin D supplements. This gap may accelerate the development and approval of alternative treatments, potentially altering the market landscape[2].

Key Takeaways

• NATPARA was approved by the FDA based on a successful 24-week clinical trial demonstrating its efficacy in managing hypoparathyroidism.
• The drug faces significant manufacturing and supply challenges, leading to its discontinuation by the end of 2024.
• The hypoparathyroidism treatment market is growing, driven by R&D investments and government support, but is restrained by the high cost and side effects of available treatments.
• The discontinuation of NATPARA production will impact patients and may accelerate the development of alternative treatments.

Frequently Asked Questions (FAQs)

What is NATPARA used for?

NATPARA is used to treat hypoparathyroidism, a rare condition characterized by low levels of parathyroid hormone, leading to low blood calcium levels.

What were the key findings of the clinical trials for NATPARA?

The clinical trials showed that NATPARA significantly reduced the need for oral calcium and active vitamin D in patients with hypoparathyroidism, with 54.8% of patients achieving the primary efficacy endpoint compared to 2.5% on placebo.

Why is Takeda discontinuing the production of NATPARA?

Takeda is discontinuing the production of NATPARA due to unresolved manufacturing issues, including contamination of rubber particles from the drug’s injector cartridge.

What are the potential side effects of NATPARA?

NATPARA is associated with potential side effects including a risk of osteosarcoma, high blood calcium levels, and reduced sense of touch or pain sensation in joints.

How will the discontinuation of NATPARA impact the market?

The discontinuation of NATPARA will leave a gap in treatment options for patients with hypoparathyroidism, potentially accelerating the development and approval of alternative treatments and altering the market landscape.

Cited Sources

1. FDA, "Drug Trials Snapshot: NATPARA (parathyroid hormone)".
2. BioPharma Dive, "Takeda to stop making parathyroid drug Natpara in 2024 after failing to resolve production issues".
3. Future Market Insights, "Hypoparathyroidism Treatment Market Analysis & Trends".
4. Natpara.com, "Phase 3 Clinical Trial Results | NATPARA® (parathyroid hormone)".
5. SNS Insider, "Hypoparathyroidism Treatment Market Size, & Global Outlook".