The Drug Development Situation of Cardiovascular Disease

• Posted by Samantha James January 29, 2021 Filed in Arts & Culture 172 views
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  Cardiovascular disease (CVD) is the leading cause of death worldwide. According to statistics from the World Health Organization (WHO), nearly 18 million people die from CVD each year, accounting for more than 30% of the total deaths worldwide. Though the high mortality and morbidity remain high, but drug development is not satisfactory.

  In terms of the number of new drugs approved by the U.S. Food and Drug Administration (FDA) from 2012 to 2019, CVD new drugs account for less than 10% of all indications, which is much lower than tumor new drugs. The clinical urgently need new treatment drugs and treatment strategies for CVD, which is a major global public health problem.

  Recently, on the eve of the 2020 European Society of Cardiology (ESC) annual meeting, Bayer held an online meeting. Several cardiovascular experts from the United Kingdom, Singapore, and Germany discussed the status of cardiovascular treatment. In-depth discussions, combined with a number of recent important clinical research results, discussed the future development direction of CVD management and treatment.

  1. Vericiguat brings new possibilities for the treatment of heart failure

  Carolyn Lam, a professor at the National University of Singapore School of Medicine, said that about 60 million people worldwide suffer from heart failure, and one-fifth of the elderly are at risk of heart failure. The quality of life and prognosis of patients have been severely affected. After five years of illness, 50% of patients may die. The result is similar to many cancers, but it has not received enough attention.

  The early symptoms and signs of heart failure are mainly dyspnea and fatigue, which are relatively insidious; most patients with heart failure cannot be diagnosed as early as possible, nor are they found in the early stage of the disease, until they finally appear in the hospital due to decompensated heart failure.

  Although we have provided patients with conventional heart failure treatment drugs in accordance with existing guidelines, patients still have symptoms and signs of disease progression, and require intensive treatment including emergency medical treatment, intravenous injection, and hospitalization. At the beginning of a certain heart failure worsening, more and more heart failure worsening may occur, showing a downward trend, and eventually heart failure and death.

  In response, Carolyn Lam called for more attention to the issue of heart failure. She pointed out that water-soluble guanylate cyclase is essential for the regulation of blood vessel and heart function. In patients with heart failure, guanylate cyclase cannot be fully activated due to impaired production and activity of nitric oxide, which often leads to abnormal heart and blood vessel functions.

  Vericiguat is a direct stimulator of soluble guanylate cyclase that is in the development stage and only needs to be taken once a day. It can activate guanylate cyclization that cannot be fully activated in patients with heart failure due to impaired nitric oxide production and activity enzymes, repair abnormal heart and blood vessel function. The results of the study found that the addition of vericiguat can significantly reduce the composite endpoint of cardiovascular death and heart failure hospitalization by 10%, and the absolute risk is reduced to 4.2/100 patient-years.

  Carolyn Lam said that Vericiguat has the potential to become an important new treatment on the basis of recommended treatments in conventional guidelines. This is because Vericiguat can effectively restore the function of the special pathway NO-sGC-cGMP, which is also a new area that has not been touched by the previous therapies.

  1. Rivaroxaban benefits more patients with arterial disease

  The formation of red and white blood clots plays an important role in coronary artery and peripheral artery disease. White blood clots are mainly caused by platelets, while red blood clots are produced by blood clotting. In fact, these two pathways are closely related to each other, and platelet aggregation strongly stimulates the production of thrombin, leading to blood clotting. Vice versa, thrombin is a potent activator of platelet aggregation.

  "In the past, we hoped that the combined application of two different types of antithrombotic drugs can achieve targeted effects, but previous studies have shown that whether it is a single vitamin K antagonist or some new oral anticoagulants combined with aspirin treatment, it does not reduce the cardiovascular event risk.” At this meeting, Professor Rupert Bauersachs of the University of Frankfurt, Germany conducted an in-depth interpretation and comparison of the trial design and results of the two recent clinical studies COMPASS and VOYAGER PAD. They found that the extremely low-dose rivaroxaban (2.5 mg bid) can reduce the risk of cardiovascular disease, but it does not increase the risk of bleeding.

  The subjects of the COMPASS study were patients with stable atherosclerotic cardiovascular disease who received rivaroxaban (2.5 mg bid) + aspirin (100 mg qd), rivaroxaban (5 mg bid) or aspirin (100 mg bid). .

  The study results suggest that compared with aspirin alone, rivaroxaban + aspirin can significantly reduce the incidence of composite endpoints (stroke, cardiovascular death, and heart attack) by 24%, and can also significantly reduce the risk of cardiovascular death and stroke, respectively reaching 22% and 42%, reducing the risk of heart attack and all-cause death by 14% and 18%, but there was no significant difference between the two groups of intracranial hemorrhage or fatal hemorrhage. Due to the significant benefits, the study was terminated early.

  Based on the results of the COMPASS Phase III study, rivaroxaban 2.5 mg bid combined with aspirin has also been recommended by many latest guidelines. It is currently the only approved combination of aspirin for chronic CAD or PAD patients who are at high risk of ischemic events to reduce major heart problems. Non-vitamin K antagonist oral anticoagulants for the risk of vascular events.

  The VOYAGER study subjects were patients with peripheral arterial disease who underwent lower extremity revascularization due to ischemic symptoms. It was found that rivaroxaban combined with aspirin can reduce the main composite endpoint events (acute limb ischemia, vascular disease-related amputation, heart disease) compared with aspirin alone. The risk of attack, ischemic stroke or cardiovascular death) reached 15%, and the risk of acute limb ischemia was reduced by 33%. The risk of future revascularization and hospitalization was significantly reduced by 12% and 28%, respectively.

  1. Finerenone delays the progression of chronic kidney disease

  George Bakris, a professor at Chicago Medical College in Illinois, USA, pointed out that diabetes is one of the important causes of renal failure. The impaired renal function of patients is often asymptomatic. When detected, renal function often has irreversible decline, and blood pressure is controlled. , Blood sugar and slowing down inflammation are important measures to delay renal function decline.

  The non-steroidal selective mineralocorticoid receptor antagonist finerenone, which is in the research and development stage, has been shown to reduce the harmful effects of mineralocorticoid receptor overactivation-kidney and heart damage.

  Finerenone is a new type of non-steroidal selective mineralocorticoid receptor antagonist (MRA) in the research and development stage. It has been proven to reduce the harmful effects caused by the excessive activation of mineralocorticoid receptors, and its heart and kidney benefits mainly based on the results of Phase III FIDELIO-DKD clinical research.

  The Phase III trial of Finerenone included 13,000 patients with chronic kidney disease with type 2 diabetes. FIDELIO included 5,700 patients with diabetic nephropathy to evaluate the effectiveness and safety of finerenone in reducing renal failure and renal disease progression. It has reached the top End of validity.

  The FIDELIO-DKD study is part of the largest phase III clinical trial in patients with chronic kidney disease with type 2 diabetes. A total of 13,000 people with different disease severity (from early kidney damage to late kidney disease), this study evaluated the efficacy and safety of Finerenone on the basis of standard treatment in patients with chronic kidney disease with type 2 diabetes.

  The results show that Finerenone can delay the progression of chronic kidney disease. On the basis of standard treatment, compared with placebo, Finerenone can significantly reduce the primary composite endpoint (chronic kidney disease progression, renal failure or death from kidney disease) and the key secondary composite endpoint (cardiovascular death or nonfatal cardiovascular event).

  At the meeting, George Bakris made an accurate analysis of the physiopathological changes of DKD, emphasizing that "protecting renal function is very important, the earlier the protection, the better the outcome", and on this basis, combined with the new drug Finerenone and related the latest progress of FIDELIO-DKD clinical research provides a special solution for DKD.

  About CD BioSciences

  CD BioSciences' cardiovascular team has extensive experience and knowledge in cardiovascular disease progression, scientific methodology, and evolving regulatory requirements, which are necessary to bring medicines to treat or prevent heart disease to the market. The company uncovers new opportunities for cardiovascular drug development for a variety of cardiovascular diseases. These diseases fall into three main categories: cardiometabolic sisease, heart disease and vascular disorders.

  Moreover, CD Biosciences’ clinical trial services focus on the entire clinical trial lifecycle including bioanalytical lab testing, clinical pharmacology, first-in-human (FIH), proof of concept (POC), early phase trials, phase IIa trials, phase IIb-III trials, phase IIIb-IV trials, CDM analysis and reporting.