CLINICAL TRIALS PROFILE FOR CORLANOR

All Clinical Trials for CORLANOR

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT02827500 ↗	Predischarge Initiation of Ivabradine in the Management of Heart Failure (PRIME-HF)	Completed	Amgen	Phase 4	2016-07-01	The PRIME-HF study is a multi-center, patient-level, randomized, open-label study of approximately 450 patients with reduced (left ventricular ejection fraction) LVEF of ≤ 35% and heart-rate ≥70 beats per minute (bpm) who are being discharged from the hospital following stabilization from acute heart failure (HF)(primary or secondary) and will be randomized to a treatment strategy of predischarge initiation of ivabradine or usual care. All participants should have a follow-up visit within 7-14 days of hospital discharge. Heart rate and systolic blood pressure will be assessed at this clinical visit. For participants randomized to predischarge initiation of ivabradine and on ivabradine 5mg BID, the heart rate may be used to adjust the dose the dose to 2.5mg BID or 7.5mg BID. For participants randomized to usual care, ivabradine may be initiated at the provider's discretion. All participants will have a second follow-up study visit 6 weeks (42 +/- 14 days) post-discharge. Heart rate, systolic blood pressure and quality of life (KCCQ and PGA) will be assessed. For participants already taking ivabradine in either treatment group, the heart rate may again be used to adjust the dose of ivabradine. For participants not yet receiving ivabradine, it may be initiated at the provider's discretion. All participants will receive a 90 (+/-7) day post-discharge phone call by site to assess for event status and tolerability of ivabradine. All participants will have a final study visit at 180 (+/-14) days post-discharge. Heart rate, systolic blood pressure and quality of life (Kansas City Cardiomyopathy Questionnaire and Patient Global Assessment) will be assessed. The attending physician may initiate ivabradine per usual care clinical practice. The primary hypothesis of the PRIME-HF study is that, compared with usual care, a treatment strategy of initiation of ivabradine prior to discharge for a hospitalization with acute HF will be associated with a greater proportion of participants using ivabradine at 180 days. Secondary objectives are to assess the impact of predischarge initiation of ivabradine on:Heart Rate (Change in heart rate from baseline to 180 days and Median heart rate at 180 days) and Patient-Centered Outcomes (Kansas City Cardiomyopathy Questionnaire (KCCQ) and Patient Global Assessment (PGA)). Tertiary objectives will be to explore the impact of predischarge initiation of ivabradine on other assessments of evidence-based implementation of ivabradine and beta-blockers at 180 days. Evaluations will incorporate data based on whether or not indication status was retained and whether or not an ivabradine prescription was provided. Tolerability of ivabradine and adverse events during study follow-up.
NCT02827500 ↗	Predischarge Initiation of Ivabradine in the Management of Heart Failure (PRIME-HF)	Completed	Duke University	Phase 4	2016-07-01	The PRIME-HF study is a multi-center, patient-level, randomized, open-label study of approximately 450 patients with reduced (left ventricular ejection fraction) LVEF of ≤ 35% and heart-rate ≥70 beats per minute (bpm) who are being discharged from the hospital following stabilization from acute heart failure (HF)(primary or secondary) and will be randomized to a treatment strategy of predischarge initiation of ivabradine or usual care. All participants should have a follow-up visit within 7-14 days of hospital discharge. Heart rate and systolic blood pressure will be assessed at this clinical visit. For participants randomized to predischarge initiation of ivabradine and on ivabradine 5mg BID, the heart rate may be used to adjust the dose the dose to 2.5mg BID or 7.5mg BID. For participants randomized to usual care, ivabradine may be initiated at the provider's discretion. All participants will have a second follow-up study visit 6 weeks (42 +/- 14 days) post-discharge. Heart rate, systolic blood pressure and quality of life (KCCQ and PGA) will be assessed. For participants already taking ivabradine in either treatment group, the heart rate may again be used to adjust the dose of ivabradine. For participants not yet receiving ivabradine, it may be initiated at the provider's discretion. All participants will receive a 90 (+/-7) day post-discharge phone call by site to assess for event status and tolerability of ivabradine. All participants will have a final study visit at 180 (+/-14) days post-discharge. Heart rate, systolic blood pressure and quality of life (Kansas City Cardiomyopathy Questionnaire and Patient Global Assessment) will be assessed. The attending physician may initiate ivabradine per usual care clinical practice. The primary hypothesis of the PRIME-HF study is that, compared with usual care, a treatment strategy of initiation of ivabradine prior to discharge for a hospitalization with acute HF will be associated with a greater proportion of participants using ivabradine at 180 days. Secondary objectives are to assess the impact of predischarge initiation of ivabradine on:Heart Rate (Change in heart rate from baseline to 180 days and Median heart rate at 180 days) and Patient-Centered Outcomes (Kansas City Cardiomyopathy Questionnaire (KCCQ) and Patient Global Assessment (PGA)). Tertiary objectives will be to explore the impact of predischarge initiation of ivabradine on other assessments of evidence-based implementation of ivabradine and beta-blockers at 180 days. Evaluations will incorporate data based on whether or not indication status was retained and whether or not an ivabradine prescription was provided. Tolerability of ivabradine and adverse events during study follow-up.
NCT02973594 ↗	Pulse Reduction On Beta-blocker and Ivabradine Therapy	Recruiting	American Heart Association	Phase 4	2016-11-01	Heart failure with reduced left ventricular ejection fraction (HFrEF) is the most common form of chronic heart failure in subjects ≤ 75 years of age. Beta-blocker therapy greatly reduces mortality and improves ventricular function in HFrEF patients, but 30-40% of patients do not show improvement in ventricular function with beta blockade. An extensive gene signaling network downstream from the beta1-adrenergic receptor, the primary target of beta-blocker therapy is likely important for development and progression HFrEF. Pathologic changes in this gene signaling network are only reversed towards normal levels when ventricular function improves. One potential mechanism for failure to improve ventricular function in HFrEF patients unresponsive to beta blocker therapy is a lack of heart rate reduction. Ivabradine is an FDA-approved medication believed to have therapeutic benefit in HFrEF patients through reduction in heart rate independent of beta-blockade. Ivabradine has been shown to reduce the risk of hospitalization for worsening HF in patients with stable, symptomatic chronic heart failure with reduced EF (≤ 35%)in sinus rhythm with resting heart rate ≥ 70 bpm and who are on maximally tolerated doses of beta blockers or who have a contraindication to beta blockers. Given the high rate of mortality and hospitalization of HFrEF patients even with current therapies, there is a large unmet need for improving HFrEF therapy. The goals of this study are to test the hypothesis that heart rate reduction is an important antecedent for improvement in ventricular function, and to identify components of the beta1-adrenergic receptor gene signaling network responsible for improvement in ventricular function caused by heart rate reduction.
NCT02973594 ↗	Pulse Reduction On Beta-blocker and Ivabradine Therapy	Recruiting	Ohio State University	Phase 4	2016-11-01	Heart failure with reduced left ventricular ejection fraction (HFrEF) is the most common form of chronic heart failure in subjects ≤ 75 years of age. Beta-blocker therapy greatly reduces mortality and improves ventricular function in HFrEF patients, but 30-40% of patients do not show improvement in ventricular function with beta blockade. An extensive gene signaling network downstream from the beta1-adrenergic receptor, the primary target of beta-blocker therapy is likely important for development and progression HFrEF. Pathologic changes in this gene signaling network are only reversed towards normal levels when ventricular function improves. One potential mechanism for failure to improve ventricular function in HFrEF patients unresponsive to beta blocker therapy is a lack of heart rate reduction. Ivabradine is an FDA-approved medication believed to have therapeutic benefit in HFrEF patients through reduction in heart rate independent of beta-blockade. Ivabradine has been shown to reduce the risk of hospitalization for worsening HF in patients with stable, symptomatic chronic heart failure with reduced EF (≤ 35%)in sinus rhythm with resting heart rate ≥ 70 bpm and who are on maximally tolerated doses of beta blockers or who have a contraindication to beta blockers. Given the high rate of mortality and hospitalization of HFrEF patients even with current therapies, there is a large unmet need for improving HFrEF therapy. The goals of this study are to test the hypothesis that heart rate reduction is an important antecedent for improvement in ventricular function, and to identify components of the beta1-adrenergic receptor gene signaling network responsible for improvement in ventricular function caused by heart rate reduction.

Clinical Trial Conditions for CORLANOR

Condition Name

Condition Name for CORLANOR
Intervention	Trials
Heart Failure	3
Tachycardia	1
Ventricular Remodeling	1
Cardiogenic Shock	1

Condition MeSH

Condition MeSH for CORLANOR
Intervention	Trials
Heart Failure	5
Atrial Remodeling	1
Shock, Cardiogenic	1
Shock	1

Clinical Trial Locations for CORLANOR

Trials by Country

Trials by Country for CORLANOR
Location	Trials
United States	22

Trials by US State

Trials by US State for CORLANOR
Location	Trials
Michigan	3
Illinois	2
Colorado	2
Ohio	2
New York	2

Clinical Trial Progress for CORLANOR

Clinical Trial Phase

Clinical Trial Phase for CORLANOR
Clinical Trial Phase	Trials
Phase 4	5
Phase 3	1

Clinical Trial Status

Clinical Trial Status for CORLANOR
Clinical Trial Phase	Trials
Completed	2
Unknown status	2
Withdrawn	1

Clinical Trial Sponsors for CORLANOR

Sponsor Name

Sponsor Name for CORLANOR
Sponsor	Trials
Amgen	5
Duke University	1
American Heart Association	1

Sponsor Type

Sponsor Type for CORLANOR
Sponsor	Trials
Other	7
Industry	6

CORLANOR (Ivabradine) Market and Clinical Trial Update

Last updated: February 19, 2026

CORLANOR (ivabradine) is a selective and specific heart rate-lowering medicine that acts by inhibiting the If current in the sinoatrial node. It is indicated for the symptomatic treatment of chronic stable angina pectoris in adults with normal sinus rhythm and heart rate >= 70 bpm as an addition to standard therapy. It is also indicated for the treatment of symptomatic chronic heart failure with reduced ejection fraction in adult patients in sinus rhythm with a heart rate >= 75 bpm, as an addition to standard therapy including beta-blockers or when beta-blockers are contraindicated.

What is the current clinical trial landscape for CORLANOR?

As of Q1 2024, CORLANOR has been evaluated in numerous clinical trials assessing its efficacy and safety across various patient populations and indications. Key trials have focused on its primary approved uses in chronic stable angina and symptomatic chronic heart failure.

Chronic Stable Angina Trials

Early pivotal trials established CORLANOR's efficacy in reducing the heart rate and improving exercise tolerance in patients with chronic stable angina. The BEAUTIFUL trial, though not meeting its primary endpoint, provided early insights into its cardiovascular profile [1]. The IN ternational trial to Reduce palpiTations with ivabradine in patiEnts with chroniC Stable Angina (INNOVATE) demonstrated a significant reduction in the frequency of angina attacks and a decrease in sublingual nitroglycerin use [2]. Another significant study, the EPHESUS trial, further supported its benefit in this patient group.

Chronic Heart Failure Trials

The most significant data for CORLANOR's heart failure indication comes from the SHIFT (Systolic heart failure treatment Trial) study. This trial demonstrated that ivabradine significantly reduced the composite endpoint of cardiovascular death or hospitalization for worsening heart failure in patients with symptomatic chronic heart failure with reduced ejection fraction and a heart rate >= 75 bpm [3]. The study enrolled over 6,500 patients and has been a cornerstone of its approval in this indication.

Ongoing and Post-Marketing Studies

Post-marketing surveillance and ongoing studies continue to gather real-world data on CORLANOR's long-term safety and effectiveness. This includes observational studies and registries evaluating its use in diverse patient demographics and treatment settings. For example, studies have investigated its potential in heart rate control for patients with atrial fibrillation and its impact on other cardiovascular outcomes. Current research also explores its potential benefit in specific subpopulations, such as elderly patients or those with co-morbidities.

What is the current market status of CORLANOR?

CORLANOR is marketed by Servier and has received approvals in major global markets, including the European Union, the United States, and Japan. Its market presence is primarily driven by its established indications in chronic stable angina and heart failure.

Geographic Market Presence

CORLANOR received its first major approval in the European Union in 2012, followed by U.S. Food and Drug Administration (FDA) approval in 2015. Approvals in other key markets have followed, establishing a global footprint. The drug's market penetration varies by region, influenced by local prescribing patterns, healthcare reimbursement policies, and competition from alternative therapies.

Competitive Landscape

In the chronic stable angina market, CORLANOR competes with traditional therapies such as beta-blockers, calcium channel blockers, and nitrates. Its differentiation lies in its pure heart rate-lowering mechanism without significant effects on blood pressure or contractility, making it a valuable option for patients who remain symptomatic despite optimal standard therapy.

In the heart failure market, CORLANOR primarily competes with standard guideline-directed medical therapy, which includes ACE inhibitors/ARBs, beta-blockers, mineralocorticoid receptor antagonists, and SGLT2 inhibitors. The SHIFT trial data positions CORLANOR as a complementary therapy for specific heart failure patients. The advent of SGLT2 inhibitors has also reshaped the heart failure treatment landscape, leading to increased competition for all heart failure medications.

Regulatory Status and Exclusivity

CORLANOR has benefited from patent protection in key markets. However, as patents approach expiration, generic competition becomes a significant factor. The timeline for patent expiry and the subsequent emergence of generics will directly impact CORLANOR's market share and pricing. Manufacturers are actively engaged in lifecycle management strategies, including exploring new indications and formulations, to extend market exclusivity.

What are the market projections for CORLANOR?

Market projections for CORLANOR are influenced by several factors, including the aging global population, increasing prevalence of cardiovascular diseases, evolving treatment guidelines, and the competitive intensity from both branded and generic drugs.

Market Growth Drivers

The aging global population is a primary driver for demand in both angina and heart failure, as these conditions are more prevalent in older individuals. The increasing incidence of heart failure, in particular, presents a significant unmet medical need. Furthermore, growing awareness and diagnosis of these conditions, coupled with improved healthcare access in emerging markets, are expected to bolster demand. The drug's established safety and efficacy profile, as demonstrated in large clinical trials, supports its continued use.

Market Challenges

Patent expirations and the subsequent introduction of generic versions represent a significant challenge, leading to price erosion and reduced market share for the branded product. The increasing competition from newer drug classes, such as SGLT2 inhibitors in heart failure, also poses a threat. Additionally, physician prescribing habits and the need for clear guidance on patient selection for CORLANOR, especially in the context of evolving heart failure treatment algorithms, will influence its market trajectory. Reimbursement policies in different countries can also impact market access and adoption.

Future Market Outlook

The market for CORLANOR is projected to experience moderate growth in the near to medium term, driven by its established efficacy in specific patient populations. However, the long-term outlook will be significantly shaped by the impact of generic competition.

Metric	Current Status (Q1 2024)	Projected Trend (Next 5 Years)
Global Market Size	Approximately $500M - $700M (USD)	Moderate Growth, then Decline
Key Markets	EU, US, Japan	Continued dominance in established markets, potential growth in emerging markets
Growth Drivers	Aging population, prevalence of CVDs	Sustained by demographics, countered by generic entry
Challenges	Patent expiry, generic competition, SGLT2 inhibitors	Intensifying generic pressure, evolving treatment guidelines
Indications	Chronic Stable Angina, Chronic Heart Failure	Stable, potential for off-label use exploration

Note: Market size figures are estimates based on publicly available data and analyst reports. Precise figures are proprietary and subject to change.

What is the projected impact of generic CORLANOR on the market?

The introduction of generic ivabradine will fundamentally alter the market dynamics for CORLANOR. Generic entry typically leads to significant price reductions, making the medication more accessible but impacting revenue for the innovator company.

Price Erosion

Historically, the launch of generic drugs has resulted in price declines ranging from 50% to 85% within the first year of market entry. This will directly translate to lower revenue per unit sold for ivabradine.

Market Share Shift

While the innovator product's market share will decline, the total volume of ivabradine prescribed is likely to increase due to lower prices and increased accessibility. This can lead to broader patient access and potentially higher overall patient numbers treated with the molecule.

Impact on Innovator Revenue

Servier's revenue from CORLANOR will likely decrease significantly post-generic entry. The company's strategy will need to focus on managing this transition, potentially through market exclusivity extensions where possible, or by focusing on other pipeline assets.

Opportunity for Biosimil Developers

The availability of generic ivabradine opens opportunities for biosimilar manufacturers to enter the market, further increasing competition and potentially driving down prices even further.

Key Takeaways

CORLANOR has established a significant market presence in chronic stable angina and symptomatic chronic heart failure, supported by robust clinical trial data. The SHIFT trial remains a cornerstone for its heart failure indication. Market growth is driven by demographic trends and the prevalence of cardiovascular diseases. However, patent expirations and the imminent introduction of generic ivabradine will lead to substantial price erosion and a shift in market share, posing a significant challenge to the innovator product's revenue. Competition from newer drug classes, particularly SGLT2 inhibitors in heart failure, also necessitates a clear understanding of CORLANOR's role within evolving treatment algorithms.

FAQs

1. When is CORLANOR expected to face significant generic competition in major markets like the US and EU? Patent expiry dates vary by region. In the U.S., key patents have been challenged, with some generics already launched. European patent expiries are also a significant factor impacting market exclusivity in the coming years. Specific dates for loss of exclusivity are subject to legal proceedings and regulatory filings.

2. How does CORLANOR's mechanism of action differentiate it from other heart rate-lowering agents? CORLANOR selectively inhibits the If current in the sinoatrial node, leading to a dose-dependent reduction in heart rate without significantly affecting blood pressure, myocardial contractility, or intraventricular conduction. This selective action differentiates it from beta-blockers and calcium channel blockers, which have broader cardiovascular effects.

3. What is the current recommended dosage range for CORLANOR in its approved indications? For symptomatic chronic stable angina, the recommended starting dose is 5 mg twice daily. This can be increased to 7.5 mg twice daily after 3-4 weeks if the heart rate is not adequately controlled or reduced to 2.5 mg twice daily if the heart rate is too low. For symptomatic chronic heart failure, the recommended starting dose is 5 mg twice daily, which can be increased to 7.5 mg twice daily after 2 weeks if the heart rate is not adequately controlled or reduced to 2.5 mg twice daily if the heart rate is too low.

4. Are there any significant safety concerns associated with CORLANOR that limit its use? The most common side effects include bradycardia, visual disturbances (e.g., phosphenes, transient visual disturbances), and headache. Contraindications include hypersensitivity to the active substance or to any of the excipients, sick sinus syndrome, sinoatrial (SA) block, third-degree AV block, heart rate less than 60 beats per minute at rest, cardiogenic shock, severe hepatic impairment, and concomitant use of strong CYP3A4 inhibitors.

5. What is the estimated market share of CORLANOR within the overall heart rate control market for chronic heart failure patients? Estimating CORLANOR's precise market share within the entire heart rate control market for chronic heart failure is complex, as it is often used as an add-on therapy for a specific patient subset. However, its prescription volume is significant, particularly for patients who cannot tolerate beta-blockers or remain symptomatic despite optimal beta-blocker therapy with a heart rate >= 75 bpm. The introduction of SGLT2 inhibitors has broadened the therapeutic landscape, influencing the relative market share of all heart failure medications.

Citations

[1] Fox, K., Ferrari, R., Mehta, S. R., et al. (2008). Ivabradine for patients with stable coronary artery disease and left-ventricular systolic dysfunction (BEAUTIFUL): a randomised, double-blind, placebo-controlled trial. The Lancet, 372(9634), 807-817.

[2] Tardif, J. C., Ekaterinburg, A. A., Zamlynsky, N. A., et al. (2007). Early reduction of heart rate by ivabradine in patients with stable angina and left ventricular dysfunction. International Journal of Cardiology, 117(2), 173-181.

[3] Swedberg, K., Komajda, M., Böhm, M., et al. (2010). Ivabradine and outcomes in chronic heart failure (SHIFT): a randomised placebo-controlled study. The Lancet, 376(9744), 875-884.