Developing novel treatments in cardiovascular diseases
Cardiovascular disease is the number 1 cause of death globally, killing nearly twice as many people as cancer. It is a group of disorders of the heart and blood vessels. An estimated 17.8 million people died from cardiovascular diseases in 2017, a figure estimated to increase to 22.2 million people annually by 2022. Of these deaths, approximately 85% are due to heart attacks and the thrombotic stroke. There are both common and rare diseases among cardiovascular diseases.
Many cardiovascular diseases affect older patients and reduce their quality of life, then indirectly or directly lead to an early death. Unfortunately, existing treatment options are insufficient and the burden on society is high. In the EU, this disease group is estimate to cost €210 billion annually; in the US, $555 billion is estimated annually in 2017.
Cereno Scientific combines an extensive experience in cardiovascular diseases with epigenetic modulation in a novel approach to develop new treatments for patients in need. The aim is to use epigenetic modulating drugs to improve the health of cardiovascular patients, both in common and rare diseases.
Cereno’s focus is to develop novel treatments in cardiovascular diseases that offer better efficacy and fewer side effects compared with today’s available drugs.
Epigenetic modulation, the alteration of gene expression without altering genetic material
Epigenetic modulation is the alteration of gene expression without altering genetic material, in which histone deacetylase (HDAC) inhibition plays an important role. To carry out gene expression, cells must control the coiling and uncoiling of DNA around the terminal tails of core histones. HDAC inhibitors cause epigenetic modulation by blocking the actions that either leads to less compact and more transcriptionally active chromatin or form a condensed and transcriptionally silenced chromatin, resulting in either in the up-regulation or the repression of genes. Epigenetic modulation has in recent years played a critical role in new therapies within oncology, but the use of epigenetic modulation in cardiovascular diseases has just begun.
Around 95% of rare diseases are without approved treatment
There are around 6-8,000 rare diseases, affecting more than 300 million people around the world. Yet around 95% of rare diseases currently have no approved treatment. The definition of what constitutes a rare disease varies; in the US, a rare disease is defined as a condition that affects fewer than 200,000 people while in the EU it is when it affects fewer than 1 in 2,000 people.
Rare diseases became known as orphan diseases because drug companies were not interested in adopting them to develop treatments. In the US, the Orphan Drug Act was established to create financial incentives to encourage companies to develop new drugs for rare diseases.
PAH, pulmonary arterial hypertension
The rare disease pulmonary arterial hypertension (PAH) is a specific form of pulmonary hypertension. The disease causes the blood pressure in the lungs to become abnormally high and it affects around 5-15 per 100,000 people globally. PAH is a progressive disease with various etiologies that eventually leads to heart failure and poor lung function. Patients with PAH have a serious prognosis with a 5-year mortality rate of around 30%, however, their quality of life deteriorates substantially long before that. Today, the life expectancy of a PAH patient without treatment is 2.5 years, which extends to 7.5 years with modern therapeutics.
Most PAH cases have no specific known cause. The disease is characterized by an increase in the pulmonary pressure secondary to a thickening of the walls of the pulmonary arteries, ie the blood vessels leading from the right side of the heart to the lungs. This impedes blood flow and causes high blood pressure in the lungs, at later stages by locally blood clots (so called thromboses) are also formed.
The disease has major impact on the individuals’ level of function and causes, shortness of breath, fatigue, chest pain, reduced ability to work, unnatural swelling, fainting and heart palpitations. This is also of significant importance for their physical, mental and social well-being.
There is currently no cure apart from lung transplantation, which patients are often too seriously ill to undergo when it is time. The treatments offered today are only focused on improving the patient’s level of function and involve, at best, a moderate slowdown in the development of the disease. Cereno therefore sees that there is a great need for new, disease-modifying treatments, which do not exist on the market today, that can give patients an opportunity for an improved and longer life.
The global market for PAH is estimated to amount to nearly USD 12 billion by 2027. Among the three key markets US, EU4+UK, Japan, the US accounts for close to 50% of patients but 60% of sales.
Thrombosis, a blood clot forming in deep veins
The majority of cardiovascular disease complications are caused by thrombus formation, where blood clots obstruct the cardiovascular system. This is the reason why the global anti-thrombotic drug market is estimated to grow on average 7.5% annually, resulting in a $43.4 billion market by 2025.
Venous thromboembolism (VTE) is a condition in which a blood clot forms in deep veins before traveling and lodging itself in the lungs. Every year, VTE is diagnosed in 900,000 to 2,100,000 people globally, causing over 800,000 deaths only in the US and Europe. A stroke is caused by a blood clot traveling to the heart or brain. Stroke prevention in atrial fibrillation (SPAF) is a term used to describe stroke prevention in the management of atrial fibrillation (AF), which is defined as arrhythmia that can lead to stroke or other cardiovascular complications. AF is the most common arrhythmia, influencing the lives of approximately 38 million patients globally.
Anticoagulants are commonly used in the treatment of VTE and SPAF, however, major unmet needs remain. More specifically, current blood-thinning treatments involve serious bleeding risks, which calls for new preventive strategies.