Rare cardiovascular and pulmonary disease
Developing pioneering treatments for high unmet medical needs
Rare cardiovascular and pulmonary diseases are a diverse group of conditions that affect the heart, blood vessels, and lungs. These conditions are often difficult to diagnose and manage, and in many cases, there are limited treatment options. Cereno Scientific has a long-standing commitment to advancing treatments in the cardiovascular disease area, the indications particularly relevant to the company pipeline are further presented in this section.
Although each rare disease affects relatively few people, together they represent a major global health challenge. There are an estimated 6,000–8,000 different rare diseases, and up to 6% of people worldwide may be affected.1 This translates to about 30 million people in Europe and between 260–450 million people affected worldwide.2 Even though these diseases are individually uncommon, many of them have no effective treatments and can seriously impact a person’s quality of life.
In the cardiovascular field, rare diseases such as pulmonary arterial hypertension (PAH) present unique challenges in both diagnosis and treatment.
Similarly, rare pulmonary diseases encompass a broad range of conditions. Most of these are chronic (long-lasting) and idiopathic (without a known cause). While some are limited to the lungs, others have a systemic origin or affect multiple organs, for example, pulmonary hypertension due to interstitial lung disease (PH-ILD) and idiopathic pulmonary fibrosis (IPF).
Despite recent advances, most available treatments are symptomatic or supportive, rather than targeting the disease itself. A few newer therapies have been approved in recent years, but these are often associated with significant side effects. This underscores the ongoing need for effective treatments that not only target the disease itself but are also well-tolerated and safe.
PAH
Pulmonary Arterial Hypertension (PAH)
Pulmonary arterial hypertension (PAH) is a rare, progressive disease that affects the blood vessels in the lungs, leading to high blood pressure in the pulmonary circulation. In most cases, the cause is unknown. The disease is marked by thickening and narrowing of the small arteries in the lungs, including the development of characteristic plexiform lesions, which restrict blood flow from the right side of the heart to the lungs. Over time, these changes, combined with increased tissue scarring (fibrosis), reduce the elasticity of the blood vessels and increase resistance to blood flow. This process, known as vascular remodeling, raises the pressure in the pulmonary arteries and impairs circulation. In later stages, small blood clots (thromboses) may form locally, further worsening the condition. Ultimately, most patients develop right heart failure as the heart can no longer cope with the strain, which leads to death for most patients with PAH.
As a patient progresses in their PAH disease, the right heart and blood vessels in the lungs are increasingly strained and restricted until the heart gives up. Often only a few years after diagnosis.
PAH's annual global impact
- Approx. 80 000 people with PAH in US and EU
- Approx. 9 500 death in US and EU
- Around $3.1Bn is the societal economic cost in the US
- Around €2Bn is the societal economic cost the EU
Understanding right heart failure in PAH
As pulmonary vessels become narrowed and stiff, the right side of the heart, especially the right ventricle, must work harder to pump blood through the lungs. This extra strain can cause the heart's tricuspid valve to leak (tricuspid regurgitation), leading to fluid build-up, enlargement of the right ventricle, and reduced pumping efficiency. As illustrated below, this vicious cycle of pressure and overload weakens the heart over time, often resulting in right heart failure, the most common cause of death in patients with PAH.
Understanding right heart failure: Over time, PAH causes tricuspid regurgitation (TR) leading to the right ventricle (RV) to weaken until it fails.
Significant impact on patient’s lives
PAH significantly affects patients’ quality of life. Common symptoms include shortness of breath, fatigue, chest pain, swelling, fainting, and heart palpitations. These symptoms often limit daily activities and can severely impact physical, mental, and social well-being. According to an ongoing global survey supported by the Pulmonary Vascular Research Institute (PVRI), most PAH patients report that the disease greatly affects their day-to-day life.
Main burden according to PAH patients:
- 74 % report negative impact on employment
- 54.5 % are disabled due to pulmonary hypertension (PH)
- 60 % struggle to walk short distances and climbing stairs
PAH is more common in women, particularly between the ages of 30 and 60.5 The median age at diagnosis ranges from 53 to 69 years.6 Globally, an estimated 192,000 people are living with PAH, with roughly half of those cases found in the US and Europe.
Current treatment landscape and unmet need
PAH is a severe, debilitating condition that worsens over time and does not improve on its own. Without treatment, the average life expectancy is 2.5 years; with current standard therapies, this increases to approximately 7.5 years.7 There is currently no cure for PAH, aside from lung transplantation, a procedure that many patients are too ill to undergo.
The current standard of care includes vasodilator medications, which help relieve symptoms and may moderately slow disease progression when used in combination with supportive therapies. However, these treatments do not reverse the disease and are often associated with significant side effects, especially in patients with other health conditions. The recent approval of sotatercept (Winrevair™, Merck) marks a new development in the field, but its role in long-term treatment is still being evaluated.
Given the limitations of existing options, there is a clear and urgent need for new therapies that are not only safer and well-tolerated but also modify the disease itself—addressing the underlying mechanisms of PAH to enhance and extend patients' lives.
Treatment goals and how progress is measured
The primary goals in treating PAH are to halt disease progression, improve symptoms and physical capacity, and reverse vascular remodeling. Ultimately, the aim is to enhance quality of life, improve patient function and extend survival utilizing disease-modifying treatments.
Progress is typically measured by:
- Risk scores, such as the REVEAL risk score
- Functional class, such as NYHA/WHO, which reflects a patient's physical capacity and symptom burden
- Hemodynamic parameters, including mean pulmonary arterial pressure (mPAP) and pulmonary vascular resistance (PVR)
- Together, these indicators help guide treatment decisions and assess how well therapies are working over time.
IPF
IPF, Idiopathic Pulmonary Fibrosis
Idiopathic Pulmonary Fibrosis Idiopathic Pulmonary Fibrosis (IPF) is a rare, progressive, and fatal disease characterized by irreversible scarring (fibrosis) of the lungs. Patients experience significant symptoms, including a persistent dry cough, fatigue, and exertional dyspnea. Over time, this fibrosis leads to a gradual loss of lung function, ultimately resulting in respiratory failure. Mortality rates in IPF are comparable to those of severe cancers. There is currently no cure for IPF, and current treatments have severe tolerability issues. There is an outspoken need for new therapies that can halt and reverse disease progression, extend lifespan and improve quality of life of patients suffering from this disease.
Thrombotic indications
Thrombosis, a blood clot forming in deep veins
A dangerous thrombosis occurs when a blood clot blocks a blood vessel and it can occur in many different places in the body. There are two different forms of thrombosis: venous thrombosis and arterial thrombosis. Venous thrombosis is when the blood clot blocks a vein that carries blood from the body to the heart, and an arterial thrombosis is when the blood clot blocks an artery that carries oxygen-rich blood from the heart to the body. An occluding thrombosis is a serious complication that contributes to nearly 85 percent of all deaths in cardiovascular disease, with heart attacks and strokes being two of the most common complications. Many who have suffered a blood clot are prescribed drug treatment to prevent recurrent blood clots. In some cases, preventive drug treatment is initiated to prevent thrombosis even for those who never before suffered a blood clot when the risk is considered to be high in this individual.
Venous thrombosis consists of two types of venous thromboembolism, including the conditions deep vein thrombosis and pulmonary embolism, and stroke prevention in atrial fibrillation. Over 3.5 million cases of venous thromboembolism were diagnosed in 2021 and are considered a significant health burden, claiming over 800,000 lives each year in Europe and the US. The most common forms of arterial thrombosis include ischemic stroke and myocardial infarction, which kill more than one in four people globally. An arterial thrombotic event can also lead to poor blood flow to the extremities, which is a complication of peripheral artery disease. It is more common in the legs than in the arms because atherosclerosis is often found to a greater extent in the legs than in the arms due to higher blood pressure in the legs. About 8 million people, in the US alone, have peripheral artery disease.
Treatment for the prevention of thrombosis is a type of maintenance treatment where medicines are primarily prescribed to prevent recurrent thrombosis during different treatment periods depending on which type of thrombosis is involved. There are many anti-thrombotic drugs, so-called blood thinners on the market, which are used to prevent the formation of blood clots. These existing drugs have all different mechanisms of action, however, all have the serious and unwanted side effect of an increased risk of bleeding that can cause hospital stays and lead to death.
This is the main reason why anti-thrombotic drugs are not optimally used, but rather underutilized, i.e. not prescribed to all needing it, underdosed or used for a too short time. It is estimated that as many as 40–50 percent of people who would need anti-thrombotic drugs do not receive appropriate treatment. An effective drug without the high risk of bleeding that today's available treatments have is sought-after and could completely change the current approach to thrombosis prevention.