细胞-信号通路“心”机制——维利西呱抗心衰效果如何？价格呢？

At present, there are more than 12 million patients with heart failure in my country, and the number of patients is increasing at a rate of 3 million per year, which is increasingly endangering the health of Chinese people. As a treatment for chronic heart failure, Vericiguat's new mechanism of action has opened up a new path for the treatment of heart failure. What is the specific effect? What about price? Let’s learn more about it together!

heart failure

Heart failure, referred to as "heart failure", refers to the failure of the systolic and diastolic functions of the heart to fully discharge the blood returned to the heart from the veins, resulting in blood stasis in the venous system and insufficient blood perfusion in the arterial system, thus causing cardiac circulation disorder syndrome. This disorder syndrome is mainly manifested as pulmonary congestion and vena cava congestion. Simply put, heart failure does not mean that the heart has completely stopped working, but that the heart is weakened and cannot work as well as it normally does or pump blood throughout the body.

However, heart failure is not an independent disease, but rather a terminal stage in the development of heart disease. The vast majority of heart failures begin with left heart failure, which first manifests as pulmonary circulation congestion. The mortality rate of heart failure is comparable to that of cancer. About 20% of heart failure patients die within 1 year after diagnosis; about 50% of heart failure patients die within 5 years of diagnosis. Among people over 70 years old, one in 10 may suffer from heart failure.

Picture cut from Google, infringement will be deleted

Willisigua's "personal business card"

In May 2022, Vericiguat (Verquvo), a new anti-heart failure drug developed by Bayer, was approved by the National Medical Products Administration (NMPA) for marketing. It is used to treat patients with chronic heart failure with reduced ejection fraction (ejection fraction <45%) to reduce the risk of hospitalization for heart failure or the need for intravenous diuretic treatment. In addition, as early as the 2021 ESC heart failure guidelines, vericiguat was included for the first time in the treatment of heart failure with reduced ejection fraction.

Actual pictures of Vericigua film

Vericiguat is currently the only heart failure drug that targets cell-signaling pathways, so how exactly does it work? Vericiguat is a soluble guanylate cyclase (sGC) agonist. It can directly stimulate guanylate cyclase in a nitric oxide-independent manner when nitric oxide is insufficient, increase intracellular cyclic guanosine monophosphate (cGMP) levels, improve myocardial and vascular function, delay left ventricular remodeling, prevent or even reverse left ventricular hypertrophy, thereby improving myocardial and vascular function. Its unique mechanism of action is the key to breaking through the bottleneck of heart failure treatment and will further improve the prognosis of heart failure patients.

How effective is Vericiguat?

In March 2020, "N Engl J Med" published a phase III randomized, double-blind, placebo-controlled trial evaluating the effectiveness of veliciguat in patients with reduced ejection fraction and chronic heart failure with recent decompensated heart failure. The primary endpoint was the composite endpoint of death from cardiovascular disease or first hospitalization for heart failure. The secondary endpoint was a component of the primary outcome, hospitalization for heart failure, death from any cause, or a composite endpoint of heart failure, first hospitalization, and death from any cause.

The researchers recruited 5050 patients with chronic heart failure and ejection fraction less than 45%. These patients were randomly assigned in a 1:1 ratio to the experimental group and the placebo group. The experimental group received vericiguat (2.5 mg, once daily), and the placebo group only received placebo. In the end, 99.5% and 99.6% of the patients in the experimental group and placebo group completed the determination of the primary endpoint and secondary endpoint, respectively. The test results show:

Among patients who died from cardiovascular disease or were hospitalized for heart failure for the first time, 897 (35.5%) in the experimental group and 972 (38.5%) in the placebo group were 3% higher than the experimental group. Among patients who died due to cardiovascular disease, 414 (16.4%) in the experimental group and 441 (17.5%) in the placebo group were 1.1% higher than the experimental group. Among patients hospitalized for heart failure, 691 (27.4%) were in the experimental group and 747 (29.6%) were in the placebo group, which was 2.2% higher than the experimental group. Among the total number of people hospitalized for heart failure, 1,223 (38.3%) were in the experimental group and 1,336 (42.4%) were in the placebo group, which was 4.1% higher than the experimental group. Among patients who died from any cause or were hospitalized for the first time for heart failure, 957 patients (37.9%) in the experimental group and 1032 patients (40.9%) in the placebo group were 3% higher than the experimental group. Detailed data are shown in Figure 1.

Figure 1: Primary and secondary endpoints for the experimental and placebo groups

Patients treated with veliciguat had lower rates of death from cardiovascular causes or first hospitalization for heart failure, death from cardiovascular causes or hospitalization for heart failure, or death from any cause or first hospitalization for heart failure than patients who received placebo.

In summary, the efficacy of veliciguat in patients with reduced ejection fraction and chronic heart failure with recent decompensated heart failure is very impressive!

What is the price of Viriciguat?

The price of Vericiguat in overseas markets is not fixed due to exchange rate fluctuations. The current price is: a box of 28 tablets, 2.5mg specification, the price is about 2,500; a box of 98 tablets, 5mg specification, the price is about 5,000; a box of 98 tablets, 10mg specification, the price is about 5,500.

Medical Travel specializes in medical treatment abroad, providing targeted drugs, generic drugs, and anti-cancer drugs, etc., and providing patients with one-stop overseas medical services. Patients can turn to Medical Travel, which can safely and conveniently purchase Viriciguat for you. On the one hand, there is no need for you to travel back and forth overseas. On the other hand, Vericiguat purchased through Medical Companion Travel is more economical and is currently the most helpful drug purchasing channel for patients.

Global research and development of heart failure drugs

Currently, there are 779 drugs for heart failure, in addition to the marketed veliciguat, 387 drugs are currently in the non-development stage, 69 drugs are in the preclinical stage, 6 drugs are in the drug discovery stage, 3 drugs are in unknown clinical stages, 5 drugs are in the early clinical phase 1 stage, and 5 drugs are in the clinical phase 1 stage. There are 43 kinds of drugs, 3 kinds are in clinical phase 1/2, 75 kinds are in clinical phase 2, 7 kinds are in clinical phase 2/3, there are currently 28 kinds in clinical phase 3, and 6 kinds have been applied for marketing. I believe they will meet us in the near future. In addition, there are 147 kinds of drugs that have appeared in front of you. Today I will briefly introduce two kinds for you:

Picture cut from Wisdom Bud

Ivabradine hydrochloride

The indication of ivabradine for the treatment of reduced ejection fraction has been unanimously recommended by domestic and foreign guidelines. The "Chinese Guidelines for the Diagnosis and Treatment of Heart Failure 2018", "ACC/AHA/HFSA Guidelines for the Management of Heart Failure" and "ESC Guidelines for the Diagnosis and Treatment of Acute and Chronic Heart Failure" also unanimously recommend ivabradine for the management of patients with heart failure.

Ivabradine Hydrochloride Tablets are suitable for chronic heart failure patients with sinus rhythm and heart rate ≥75 beats/minute, and accompanied by cardiac systolic dysfunction. It can be used for the treatment of heart failure patients when beta-blockers are contraindicated or cannot be tolerated.

fenelidone

In July 2021, the US FDA approved the marketing of Kerendia. Currently, Kerendia has submitted marketing applications in China and many other countries around the world and is under review.

Finerenone, as a new generation of non-steroidal selective mineralocorticoid receptor antagonist (MRA), prevents various heart diseases caused by excessive activation of mineralocorticoid receptors by exerting anti-inflammatory and anti-fibrotic effects.

Dr. Christian Rommel said: "We are pleased that vericiguat has begun to make a difference for patients with heart failure. The new Phase III VICTOR study fulfills our mission of bringing potential benefits to more patients. In addition to this pivotal study, we are also committed to obtaining more clinical evidence of vericiguat and will announce the full plan in due course."

Dr. Christian Rommel, picture from Google, deleted if infringement

References

[1]Armstrong PW, Pieske B, Anstrom KJ, Ezekowitz J, Hernandez AF, Butler J, Lam CSP, Ponikowski P, Voors AA, Jia G, McNulty SE, Patel MJ, Roessig L, Koglin J, O'Connor CM; VICTORIA Study Group. Vericiguat in Patients with Heart Failure and Reduced Ejection Fraction. N Engl J Med. 2020 May 14;382(20):1883-1893. doi: 10.1056/NEJMoa1915928. Epub 2020 Mar 28. PMID: 32222134.

[2]Mengjia Shen, Cankun Zheng, Lu Chen, Mingjue Li, Xiaoxia Huang, Mingyuan He, Chiyu Liu, Hairuo Lin, Wangjun Liao, Jianping Bin, Shipping Cao, Yulin Liao. (2023) LCZ696 (sacubitril/valsartan) inhibits pulmonary hypertension induced right ventricular remodeling by targeting pyruvate dehydrogenase kinase 4. Biomedicine & Pharmacotherapy 162, 114569.

[3]Josephine Harrington, Jie‐Lena Sun, Gregg C. Fonarow, Stephen B. Heitner, Punag H. Divanji, Gary Binder, Larry A. Allen, Brooke Alhanti, Clyde W. Yancy, Nancy M. Albert, Adam D. DeVore, G. Michael Felker, Stephen J. Greene. (2023) Clinical Profile, Health Care Costs, and Outcomes of Patients Hospitalized for Heart Failure With Severely Reduced Ejection Fraction. Journal of the American Heart Association 12:10.