Patients & Caregivers

ASCVD is a large subset of cardiovascular disease where cholesterol-driven blockages in arteries lead to complications such as heart attack, stroke or limb amputations. With ASCVD, high cholesterol drives the development of atherosclerotic plaque, a mixture of cholesterol, cells and cellular debris in the wall of a blood vessel that results in hardening of the arteries and can lead to heart attack or stroke. 

Approximately 54 million people in the U.S. and Europe are affected by ASCVD. Within this group, approximately 21 million individuals are not at their medically recommended LDL-C goal, despite being treated with a statin – pointing to a need for new treatment options. LDL-C goal refers to the LDL-C level that people with cardiovascular disease should aim to meet, which is approximately 70 mg/dL.

Current treatment options for people with ASCVD vary based on the type of disease they are diagnosed with and their individual risk factors. The intention of these treatments is to lower LDL-C levels, bringing individuals toward goal level. In pursuit of our company mission, Verve intends to develop single-course gene editing medicines that address a variety of different forms of ASCVD.

FH, a genetic disease often inherited from a parent, is a form of ASCVD that is characterized by extremely high LDL-C levels in the blood. Over time, LDL-C creates plaque that builds up in the arteries and reduces blood flow, potentially leading to heart attack and stroke.

There are two forms of FH – heterozygous familial hypercholesterolemia (HeFH) and homozygous familial hypercholesterolemia (HoFH).

HeFH is one form of familial hypercholesterolemia. People with HeFH may have one mutant allele, meaning the disease was passed down by one parent.

Approximately 3 million people in the U.S. and Europe have this inherited disease. Current treatment options for HeFH include statins as a first-line treatment, followed by a PCSK9 inhibitor. 

Despite available treatment options, based on a global patient registry, approximately 97% of patients with HeFH fail to achieve goal LDL-C levels.

Verve is developing VERVE-101 and VERVE-102 to address this problem. VERVE-101 and VERVE-102 are base editing medicines designed to switch off the PCSK9 gene in the liver in order to disrupt the liver’s production of the PCSK9 protein and lower blood levels of PCSK9 protein, and thereby durably lower LDL-C levels. 

HoFH, a second form of familial hypercholesterolemia, is a rare inherited disease that impacts approximately 2,800 people in the U.S. and Europe. HoFH is characterized by premature heart attack and/or stroke due to extremely high LDL-C levels in the blood, often greater than 500 mg/dL. People with HoFH have two mutant alleles, meaning the disease was passed down by both parents. 

HoFH can be diagnosed through a blood test and physical examination. This disease can be life-threatening, and early diagnosis is often critical as the condition leads to progressive and early heart disease. Current approved treatment options include statins as a first-line treatment, followed by monoclonal antibodies and PCSK9 inhibitors. 

Verve is developing VERVE-201, an ANGPTL3-inhibiting gene editing medicine. Our first clinical trial in this program will be for HoFH.

Refractory hypercholesterolemia refers to patients with ASCVD who are not at their medically recommended LDL-C goal despite being on maximally tolerated standard of care therapies. Approximately 13% of people with ASCVD fall into this category, impacting an estimated 7 million people in the U.S. and Europe. 

While current treatment options for ASCVD – including oral therapies and PCSK9 inhibitors – often do not work for this patient population, ANGPTL3 inhibition has been shown to reduce LDL-C levels for this group. Verve plans to develop VERVE-201, an ANGPTL3-inhibiting base editing medicine, for patients with refractory hypercholesterolemia.

Lipoprotein (a), or Lp(a), is an LDL-like particle with apolipoprotein B covalently linked to apolipoprotein(a) that is produced in the liver and circulates in the blood. Lp(a) is an established and genetically determined risk factor for ASCVD, stroke, thrombosis, and aortic stenosis. This increased risk is most pronounced in individuals with very high Lp(a) concentrations (e.g., ≥ 150 nmol/L). An estimated 11 million ASCVD patients have a Lp(a) concentration above this threshold.

Lp(a) concentrations are determined at birth. Lifestyle changes, such as diet and exercise, as well as currently approved lipid-lowering therapies have minimal to no impact on Lp(a) levels. Both human genetics and pharmacologic studies have validated the potential efficacy and safety of a Lp(a)-reducing medicine.