Treating Arterial Inflammation

Monday January 27, 2020

Responsible for over 840,400 deaths and nearly 1.8 million cases of heart attack and stroke each year, cardiovascular disease (CVD) remains the leading cause of death in the United States. Long-term prevention and treatment options for ischemic coronary heart disease (CHD), the most common form of CVD, include medication to control risk factors, such as low-density lipoprotein (LDL), and, for severe cases, surgical intervention. These treatments are often inadequate, only partially lowering the risk of serious cardiovascular events. Better options are needed for the millions of high-risk patients worldwide who live with CHD.

Inflammation: A Significant Risk Factor for Heart Disease

CHD is caused by the build-up of plaque inside the arteries, a condition known as atherosclerosis. Depending on the composition, plaques can be prone to burst or “rupture,” thereby obstructing blood flow to downstream tissue.

When this happens in the coronary artery it can lead to a heart attack; when it occurs in the carotid artery it can lead to a stroke.

Classically, a heart attack is associated with five major risk factors:

  1. family history of heart disease,
  2. high cholesterol,
  3. hypertension (high blood pressure),
  4. smoking, and
  5. diabetes.

However, 25% of patients who have a heart attack for the first time do not have one of these risk factors.

atherosclerosis arterial inflammation
Atherosclerosis: The build-up of plaque in the arteries

Clinical and scientific evidence now suggests that there is a sixth risk factor for a heart attack –inflammation. Inflammation is a critical factor in the development of atherosclerosis and progression to a heart attack.  In particular, people with inflammatory disorders like rheumatoid arthritis, psoriasis, and lupus are at higher risk of suffering from a heart attack due to chronic inflammation related to their condition. Inflammation is also a significant contributor to heart attack in people with type 2 diabetes.

Targeting Inflammation: A New Frontier in the Treatment of Coronary Heart Disease

In 2017, the CANTOS trial provided the first evidence that targeting inflammation with a drug could reduce risk of heart attack. The drug tested in this trial, canakinumab (also known as Ilaris™) is an immunomodulator that targets the IL-1b pathway, but, importantly, has no effect on lipid levels or triglycerides. However, treatment with canakinumab proved to have a downside – increased risk of serious infections.

Patients who received canakinumab were put at increased risk of a serious or fatal infection. This risk has been attributed to the immunosuppressive mechanism of action of the drug. The CANTOS trial demonstrated the potential for targeting inflammation to benefit patients with CHD, but also underscored the importance of finding new ways to target more specific biological pathways and thereby avoid immunosuppression and related side effects.

Abcentra: A Novel Approach to Targeting Arterial Inflammation

Leveraging this evidence and years of scientific research, Abcentra is developing new treatment options for CHD that work by targeting arterial inflammation linked to heart attacks. Abcentra’s novel approach decreases the progression of atherosclerosis by blocking inflammatory responses from oxidized lipoproteins, such as oxidized low-density lipoprotein (oxLDL) and lipoprotein(a).  Inflammation from oxidized lipoproteins are strongly implicated in atherosclerosis and CHD.

Our lead candidate, Orticumab, targets inflammation from oxLDL and is being developed for patients at significant residual risk of a heart attack due to underlying inflammation from comorbid conditions such as psoriasis, rheumatoid arthritis and lupus.

Orticumab targeting oxLDL
Orticumab targets inflammation to treat the underlying cause of disease.

The founding scientists behind Abcentra’s therapies are leading cardiologists, Jan Nilsson M.D. Ph.D. and Prediman K. Shah M.D. Dr. Nilsson is the director of the experimental cardiovascular research unit at Lund University Hospital. His work has centered on the role of immune responses against oxLDL antigens in atherosclerosis. Dr. Shah is the Director of the Oppenheimer Research Center for Atherosclerosis at Cedar-Sinai Medical Center and has dedicated his life to the understanding of heart disease. Orticumab is the result of decades of their research.

Abcentra is committed to providing treatments for accelerated atherosclerosis in patients with inflammatory diseases. We recently announced a development milestone in preparation for our latest clinical trial. To learn more about Abcentra, contact us.