The transformative potential of gene therapies in the treatment of cardiovascular diseases (CVD) has been touted for many years. But while several CVD gene therapy approaches have demonstrated promising outcomes in preclinical models, they have generally not been able to demonstrate significant effects in clinical trials. As a result, only two CVD gene therapies have been approved worldwide to date.

Human Stem Cells Institute’s Neovasculgen was approved in Russia in 2011, while Mitsubishi Tanabe Pharma’s Collategene (beperminogene perplasmid) received marketing authorisation in Japan in 2019. Both therapies are approved for the treatment of peripheral arterial disease (PAD)/peripheral vascular disease (PVD) and critical limb ischaemia. Due to the high burden and unmet needs associated with CVD, this therapy area is an attractive target for gene therapy. As with all gene therapies, however, the potential for severe or delayed adverse effects in CVD remains a major concern, and investment in the development of these therapies is a high-risk venture.

Gene therapy remains an active area of research within the CVD field, with several companies recently investing resources in these therapies. In the past month, XyloCor Therapeutics has advanced its gene therapy for refractory angina, XC001, to Phase II development, while LEXEO Therapeutics has obtained exclusive rights to three preclinical gene therapies for rare cardiac disorders such as TNNI3-associated hypertrophic cardiomyopathy (HCM) by acquiring Stelios Therapeutics.

By altering the genetic material of patients’ cells, gene therapy has the potential to transform the treatment of highly medicated and costly conditions such as heart failure and angina to one-time treatment approaches, effectively eliminating the problem of poor adherence and significantly reducing health service costs. Despite the risks, therefore, the potential returns associated with CVD gene therapies make them worthwhile for a wide range of investors.

As the leading cause of death worldwide, the human and economic burden of CVD is substantial. At present, CVDs are predominately treated with lifestyle interventions, pharmacotherapy and surgery. Patients are often advised, however, to maintain lifestyle interventions and pharmacotherapy for the remainder of their lives, which poses a risk for poor long-term adherence. Side effects attributable to many CVD drugs can also contribute to poor adherence. Common examples of these side effects include muscle pain associated with cholesterol-lowering statins and persistent cough induced by blood pressure-lowering angiotensin-converting enzyme (ACE) inhibitors. In addition, despite the many advances made in cardiac surgery in recent decades, serious complications can arise from these procedures, including infection, stroke and acute kidney injury.

According to GlobalData’s Pipeline Product database, gene therapies account for around 5% of all products in active development for CVD. There are 87 gene therapies in development for CVD worldwide from the Discovery stage to Phase III development. With 65 companies active within this space, most sponsors are only investing in a single CVD gene therapy. Highly active sponsors include Tenaya Therapeutics, Renova Therapeutics and LEXEO Therapeutics, all of which have four CVD gene therapies in development.

For drug developers, the key areas of research with the highest number of gene therapies under development are heart failure (21 therapies), ischaemia/stroke (18 therapies) and cardiomyopathy (18 therapies). This is highlighted in the following figure, which provides a breakdown of the indications for which gene therapies are in development.

Cell & Gene Therapy Coverage on Clinical Trials Arena supported by Cytiva.

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