New changes in the drug treatment pattern of primary hyperparathyroidism in the post-epidemic era

Primary hyperparathyroidism (PHPT) is a disease in which parathyroid hormones are oversynthesized and secreted by the parathyroid glands itself, resulting in abnormal calcium and phosphorus metabolism; the pathophysiology is characterized by osteocalcin dissolution and increased renal tubular calcium reabsorption , Urinary phosphorus excretion increases, which induces osteoporosis, osteomalacia, urinary calculi and other diseases
.

The clinical manifestations of PHPT are complex and diverse, even including asymptomatic onset
.

The typical PHPT usually manifests mainly in the bones and urinary system, and the digestive system, circulatory system, and nervous system may also be involved

The data in this article comes from the PDB Drug Comprehensive Database (pdb.
pharmadl.
com)
.

Epidemiological characteristics of PHPT

Epidemiological characteristics of PHPT

According to research data from Ksiser Permanente Health Care in California, the incidence of PHPT increased by three times from 1995 to 2010
.

The study also found that there are differences in PHPT between different races-African Americans have a significantly higher incidence than whites, followed by Asians, Hispanics and other races

Pathogenesis of PHPT

Pathogenesis of PHPT

The molecular mechanism of PHPT pathogenesis is not yet fully understood.
Current studies have found that gene abnormalities in the calcium-sensitive receptor signaling pathway, cyclin D1 (Cyclin D1) signaling pathway, and Wnt/β-catenin signaling pathway play a role in its pathogenesis
.

Calcium Sensitive Receptor Signaling Pathway:

A G protein-coupled receptor that is highly expressed in the parathyroid glands and kidneys.
It regulates the secretion of parathyroid hormone by detecting the level of free calcium in the blood and plays a key role in calcium homeostasis
.

When a gene mutation occurs, it will cause a bias in calcium regulation signal transduction

Wnt/β-catenin signaling pathway:

As a pathway to stimulate growth, it plays a regulatory role in embryonic development, so that cells proliferate and differentiate
.

The expression of β-catenin may increase when β-catenin gene mutation, Wnt ligand overexpression, regulation pathway inhibition or activity decrease

Cyclin D1 signaling pathway:

Cyclin D1 overexpression is an important factor in the pathogenesis of sporadic parathyroid adenomas.
As a protein that has a positive regulatory effect on the cell cycle, it can accelerate the process of the cell cycle and induce excessive proliferation of parathyroid cells
.

PHPT drug treatment

PHPT drug treatment

For PHPT patients who cannot receive surgical treatment, choosing medical medication is a relatively safe plan, the main purpose is to control hypercalcemia and reduce complications
.

Calcium mimetic compound:

Cinacalcet is a type 2 calcimimetic.
It can activate the calcium-sensitive receptors on the parathyroid glands, thereby inhibiting the secretion of PTH and effectively reducing the serum calcium level.
It is especially suitable for patients who cannot accept surgery and have obvious symptoms of hypercalcemia or Those with significantly elevated blood calcium, but Cinacalcet has no significant effect on bone density
.

Vitamin D treatment:

Vitamin D deficiency is common in many PHPT patients.
Parathyroid hormone stimulates the conversion of 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D.
Elevated 1,25-dihydroxyvitamin D may stimulate 24 - hydroxyalkyl hydrolase gene expression and increase the conversion of 25-hydroxyvitamin D to 1,24-dihydroxyvitamin D
.

Vitamin D deficiency is associated with increased parathyroid weight, increased levels of PTH, blood calcium and alkaline phosphatase, and decreased bone density.

PHPT drug therapy market

PHPT drug therapy market

From 2012 to 2020, the PHPT therapeutic drug market continued the strong momentum of the overall medical market and continued to achieve revenue growth.
Among them, calcitriol, as the first choice for vitamin D supplementation, became the "pillar" of the PHPT therapeutic market, 2012 The annual revenue of 340 million yuan is arrogant, which is basically equivalent to the combined market share of alfacalcidol and salmon calcitonin.
Since then, it has been strong and has a market share of more than 50% until 2020! In contrast, the revenues of alfacalcidol and salmon calcitonin have fallen short of expectations.
From 310 million yuan in 2012 to 280 million yuan in 2020, sales have actually declined
.

It is worth noting that Cinacalcet, as an emerging PHPT therapeutic drug, is receiving more and more attention, and its sales have taken off from 2018.

2012-2021 Q1 PHPT treatment market share change trend chart

Analyzing the market shares of various companies, because calcitriol is the absolute pillar of the market, mastering calcitriol means mastering the entire PHPT drug sales market.
This is why Roche Pharmaceuticals and Chia Tai Pharmaceutical (Qingdao) Co.
, Ltd.
started a see-saw.
Since 2012, Roche has led the list with a weak lead; since 2016, CP Pharmaceuticals has begun to exert its strength and successfully achieved a surpassing sales performance and has maintained its advantage to this day
.

2012-2021Q1 PHPT drug companies' market share share

When we analyze the market share of the PHPT therapeutic drug calcitriol in Q1 of 2021, we can clearly see that the drug market is indeed a "fairy fight", showing a high degree of monopoly.
Chia Tai Pharmaceuticals and Roche monopolize 99% of sales.
…And CP Pharma once again won the championship with a market share of more than 50%, and Chinese pharmaceutical companies have won the first place, which is worth celebrating
.

Market share of calcitriol enterprises in Q1 2021

In recent years, the incidence of PHPT has been on the rise, and the clinical manifestations have become more complex, which is prone to missed and misdiagnosed
.

It is necessary to actively improve the understanding of the disease, achieve early detection, active intervention, and it is very possible to avoid serious organ damage