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Home Bayer’s First-in-Class sGC Stimulator Verquvo (vericiguat) Receives Positive CHMP Opinion in EU and Under Regulatory Review in China for Heart Failure

Bayer’s First-in-Class sGC Stimulator Verquvo (vericiguat) Receives Positive CHMP Opinion in EU and Under Regulatory Review in China for Heart Failure

May 23, 2021 03:05 CST Updated 03:05
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Committee for Medicinal Products for Human Use

Committee for Medicinal Products for Human Use (CHMP)The Committee for Medicinal Products for Human Use (CHMP) is the committee within the European Medicines Agency (EMA) responsible for human medicines. The CHMP replaced the former Committee for Proprietary Medicinal Products (CPMP) in May 2004.The CHMP plays a vital role in the authorization of medicines in the European Union (EU). In the centralized procedure, the CHMP is responsible for: 1) conducting initial assessments of marketing authorization applications across the EU; assessing modifications or extensions to existing marketing authorizations (“variations”); considering recommendations from the Agency’s Pharmacovigilance Risk Assessment Committee regarding the safety of medicines on the market, and, where necessary, advising the European Commission to amend the marketing authorization of a medicinal product, or to suspend or withdraw it from the market.The CHMP also evaluates medicines authorized at the national level that are referred to the EMA, with the aim of maintaining a harmonized position throughout the EU.Furthermore, the CHMP and its working groups promote the development of medicines and pharmaceutical regulation by: providing scientific advice to companies researching and developing new medicines; developing scientific and regulatory guidelines to assist pharmaceutical companies in preparing marketing authorization applications for human medicines; and collaborating with international partners to harmonize regulatory requirements.

European Commission

The European Commission, abbreviated as the EU Commission, is a supranational body under the European Union. Within the EU political system, the European Commission primarily undertakes executive tasks, thus being roughly equivalent to the government in a national system. However, the European Commission has other functions as well. In particular, except for the few circumstances specified in the treaties, the European Commission is the only institution with legislative power in the EU legislative process.


May 23, 2021 News /BioonBIOON/ --Bayer(Bayer) recently announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has issued a positive opinion recommending the approval of vericiguat, a soluble guanylate cyclase (sGC) stimulator. The CHMP opinion will now be submitted to the European Commission (EC) for review, which is expected to make a final approval decision within the next two months. Once approved, vericiguat (2.5 mg, 5 mg, and 10 mg tablets) will be indicated for adult patients with symptomatic chronic heart failure with reduced ejection fraction who have stabilized following a recent decompensation event requiring intravenous (IV) therapy.

Vericiguat is an oral, once-daily, first-in-class soluble guanylate cyclase (sGC) stimulator.。Although sGC is essential for both vascular and cardiac function, impaired nitric oxide (NO) bioavailability in patients with heart failure results in insufficient sGC stimulation, leading to myocardial and vascular dysfunction.

Vericiguat was jointly developed by Merck & Co. and Bayer. The two companies entered into a global collaboration in October 2014 to develop sGC stimulators. Merck holds commercialization rights for vericiguat in the United States, while Bayer holds exclusive rights for the rest of the world.

Molecular structure of vericiguat (Image source: medchemexpress.com)

In January this year, vericiguat received USFDAApproved under the trade name Verquvo for patients with symptomatic chronic heart failure with an ejection fraction <45%, to reduce the risk of cardiovascular death and hospitalization for heart failure following a worsening heart failure event (defined as hospitalization for heart failure or treatment with outpatient intravenous [IV] diuretics for heart failure without hospitalization).

It is worth noting that,Vericiguat is the first soluble guanylate cyclase (sGC) stimulator approved for the treatment of heart failure.。Currently, vericiguat is also undergoing regulatory review in Japan, China, and other countries.in China, in late August 2020, Bayer to the National Medical Products Administration (NMPA)Submitted the marketing authorization application for vericiguat。

Patients with symptomatic chronic heart failure and reduced ejection fraction are at high risk of hospitalization following a heart failure episode requiring outpatient intravenous diuretic therapy or hospitalization. It is estimated that more than half of patients are rehospitalized within one month of discharge due to worsening heart failure, and approximately one in five patients die within two years. Upon market launch, vericiguat will provide a welcome new option for physicians, healthcare professionals, and patients.

United StatesFDAThe approval of vericiguat and the CHMP's recommendation for the approval of vericiguat were both based on the results of the pivotal Phase III VICTORIA study. Data showed that, following a worsening heart failure event,Compared with background therapy alone, vericiguat combined with background therapy significantly reduced the composite risk of cardiovascular death or hospitalization for heart failure.The positive results of the Phase III VICTORIA study were presented at the American College of Cardiology Annual Scientific Session held in March 2020.Meeting/presented at the virtual World Congress of Cardiology (ACC.20/WCC Virtual), and published in the top-tier international medical journal *The New England Journal of Medicine* (NEJM). The article is titled:Vericiguat in Patients with Heart Failure and Reduced Ejection Fraction。

Notably, VICTORIA is the first contemporary outcomes trial specifically targeting symptomatic chronic heart failure patients (ejection fraction <45%) following a worsening event. Data demonstrated that, when used in combination with available heart failure medications, once-daily 10 mg vericiguat significantly reduced the relative risk of the composite endpoint of heart failure hospitalization and cardiovascular death following a worsening event by 10% (HR=0.90; 95% CI: 0.82–0.98; p=0.019) compared with placebo, with an absolute risk reduction of 4.2 per 100 patient-years.

For many patients with heart failure, worsening events can lead to clinical deterioration and a poor prognosis, with approximately 50% of patients dying within five years of diagnosis. The VICTORIA trial is the first positive contemporary outcomes trial specifically targeting patients with symptomatic chronic heart failure with reduced ejection fraction (HFrEF) who have experienced prior worsening heart failure events. The findings of this study open up new possibilities for the treatment of chronic heart failure.

Dr. Burkert Pieske, Professor of Internal Medicine and Cardiology at Charité – Universitätsmedizin Berlin, Germany, and Principal Investigator of the Phase 3 VICTORIA study, stated: “Even when receiving guideline-directed medical therapy, many patients with heart failure still experience progressive worsening of symptoms, necessitating hospitalization or the initiation of intravenous diuretics. This remains one of the greatest unmet challenges in the management of chronic heart failure; tragically, 1 in 5 patients survives no longer than two years following a worsening heart failure event. Once approved, vericiguat will be the first therapy specifically studied in patients with recent decompensation to help break the cycle of worsening events, reduce the risk of rehospitalization, and hopefully make a meaningful difference in the lives of patients and their families.”

Dr. Christian Rommel, Executive Committee Member and Head of Research & Development, Bayer Pharmaceuticals Division, stated: “Heart failure is the leading cause of hospitalization in Europe. Given that half of patients are readmitted within 30 days of hospitalization or initiation of intravenous diuretic therapy, this places a significant burden on both patients and the broader healthcare system. We are pleased to receive the CHMP’s positive opinion on vericiguat, as it brings us closer to offering a new treatment option with the potential to alleviate this burden and help improve outcomes and the management of chronic heart failure for high-risk patients.”

Results of the VICTORIA Clinical Trial

VICTORIA was a randomized, placebo-controlled, parallel-group, multicenter, double-blind Phase III trial conducted at more than 600 clinical centers across 42 countries worldwide. The study enrolled 5,050 patients with symptomatic chronic heart failure, an ejection fraction of less than 45%, who had experienced a worsening heart failure event. In the study, patients were randomly assigned to receive once-daily vericiguat (titrated to 10 mg; n=2,526) or placebo (n=2,524), in addition to available background heart failure therapy. The primary endpoint was a composite of cardiovascular death or hospitalization for heart failure. Compared with recent heart failure outcome trials, the annual placebo event rate for the primary endpoint was more than double, and baseline levels of the clinical prognostic marker (NT-proBNP) were also more than double, indicating a higher risk of hospitalization or death among these patients.

The results showed that the study met its primary efficacy endpoint: when used in combination with available heart failure medications, compared with placebo, a once-daily 10 mg dose of vericiguat significantly reduced the composite risk of heart failure hospitalization and cardiovascular death following a worsening event by 10% (relative risk reduction: HR=0.90, 95% CI: 0.82-0.98, p=0.019); absolute risk reduction [ARR]: 4.2/100 patient-years).

This effect was consistent across most prespecified subgroups, including patients receiving or not receiving Entresto (sacubitril/valsartan). Baseline NT-proBNP levels and age were associated with the treatment effect. In this study, data indicated that most patients with NT-proBNP levels in the lower quartile range and those younger than 75 years may have derived greater benefit.

In the baseline NT-proBNP analysis, patients were divided into four quartiles. The overall treatment benefit was driven by patients in the lower three quartiles, among whom the relative risk reduction for the primary composite endpoint ranged from 18% to 27%.

In the study, vericiguat was well tolerated, consistent with the safety profile observed in previous vericiguat studies. The overall incidence of serious adverse events was similar between the vericiguat and placebo groups (32.8% vs. 34.8%). Symptomatic hypotension (9.1% vs. 7.9%) and syncope (4.0% vs. 3.5%) were more common in the vericiguat group than in the placebo group, but the differences were not statistically significant. (Bioon.com)

Original Source: Positive CHMP opinion for Bayer’s new symptomatic chronic heart failure treatment vericiguat