Cardiovascular diseases remain the leading cause of death globally, with nearly 18 million lives lost each year. But as gene therapies advance, they promise a transformative future for patients suffering from conditions such as congestive heart failure, chronic refractory angina, and cardiomyopathy.
Gene therapies have gained significant traction in the fight against heart disease. Faraz Ali, CEO of Tenaya Therapeutics, a biotech company dedicated to cardiovascular treatments, emphasized that advancements in gene therapies are pushing the boundaries of heart disease treatment. “We now have some early successes,” he stated, citing breakthroughs from Rocket Pharmaceuticals and Lexeo Therapeutics in treating genetic cardiomyopathies.
Cardiovascular diseases encompass a wide spectrum of conditions affecting the heart and blood vessels, from common ailments like heart failure and coronary artery disease to rarer disorders like Duchenne muscular dystrophy-associated cardiomyopathy. In most cases, treatment begins with lifestyle changes and medications aimed at alleviating symptoms. However, gene therapies—interventions that introduce healthy genes to restore or enhance the function of specific proteins—are emerging as a new frontier in cardiovascular care.
Ali believes the success of these early trials validates the potential of gene therapy, with clinical tools and methods advancing to deliver more precise and effective treatments.
Here are five promising gene therapies currently being explored for cardiovascular indications:
1. Renova Therapeutics’ RT-100
Indication: Congestive Heart Failure (CHF)
Renova’s RT-100 is one of the most advanced gene therapies in development for congestive heart failure (CHF), a condition that affects over six million Americans. CHF can stem from several underlying issues, including infections, blood clots, or other cardiovascular conditions.
RT-100 works by delivering the AC6 gene, which encodes a protein central to regulating heart function. The gene therapy aims to boost the AC6 protein in heart muscles, potentially improving organ function.
In Phase II clinical trials, Renova reported a significant increase in left ventricular peak, a key measure of heart function, after just four weeks. The treatment also improved left ventricular ejection fraction. While no significant safety concerns were observed, the small-scale study involving 56 patients demonstrated positive results. Renova is now preparing to submit plans for a pivotal Phase IIb/III study to the FDA, with further trials expected in the coming months.
2. XyloCor’s XC001
Indication: Chronic Refractory Angina
XyloCor Therapeutics is targeting chronic refractory angina with XC001, a therapy aimed at patients who have exhausted other treatment options and are ineligible for coronary artery bypass or percutaneous coronary intervention.
Angina is characterized by chest pain resulting from restricted blood flow to the heart. In chronic refractory cases, the pain persists despite optimal medical therapy. XC001 works by delivering the VEGF gene, promoting the growth of new blood vessels that bypass blockages and improve oxygen supply to the heart muscles.
The results from XyloCor’s Phase II EXACT clinical trial show promising improvements in exercise duration, angina frequency, and chest pain. In May 2024, the company announced plans to begin a Phase IIb study, although a detailed timeline has yet to be disclosed.
3. Regenexbio’s RGX-202
Indication: Cardiomyopathy in Duchenne Muscular Dystrophy (DMD)
Duchenne muscular dystrophy (DMD) is a rare genetic disorder that leads to muscle weakness and eventual heart failure. Regenexbio’s RGX-202 is an innovative gene therapy designed to treat cardiomyopathy, a serious heart condition that develops in DMD patients.
RGX-202 aims to deliver a microdystrophin transgene to patients, enabling them to produce a functional form of the dystrophin protein, which is essential for heart muscle function. Early clinical results from the AFFINITY DUCHENNE trial show promising expression of the microdystrophin protein, supporting the possibility of accelerated approval.
Regenexbio is expected to complete its pivotal Phase II study by December 2025, with plans to submit a Biologics License Application (BLA) in 2026.
4. AskBio’s AB-1002
Indication: Congestive Heart Failure (CHF)
AskBio, a subsidiary of Bayer, is developing AB-1002, a gene therapy that targets the downregulation of a key protein phosphatase inhibitor in the heart, potentially reversing heart failure symptoms. The therapy seeks to restore the proper functioning of heart muscles by addressing the excessive enzymatic activity that contributes to CHF.
Early Phase I data presented in November 2023 demonstrated significant improvements in left ventricular ejection fraction and overall heart function in three patients. AB-1002 is currently undergoing further trials in the Phase II GenePHIT study, which is expected to conclude in October 2026.
5. Tenaya Therapeutics’ TN-201
Indication: Hypertrophic Cardiomyopathy
Tenaya Therapeutics is developing TN-201 as a precision gene therapy for hypertrophic cardiomyopathy, a condition that leads to thickening of the heart walls and can cause severe complications, including heart failure.
TN-201 targets mutations in the MYBPC3 gene, which are present in about 20% of hypertrophic cardiomyopathy patients. By delivering a gene therapy to correct this mutation, the therapy aims to improve heart muscle function. In early Phase Ib/II trials, TN-201 showed promising results, with patients exhibiting increased protein production and improved clinical markers.
While early results were positive, the therapy faced scrutiny after the observed RNA expression levels were lower than expected based on preclinical models. Despite this, Tenaya remains committed to advancing TN-201, with further data expected in 2025.
Conclusion
Gene therapies are making significant strides in the treatment of cardiovascular diseases, offering new hope for patients with conditions that have long been difficult to treat. These five gene therapies represent just a glimpse of the potential for precision medicine to revolutionize the landscape of cardiovascular care. As trials progress and more data become available, gene therapies could become a key tool in the fight against heart disease, addressing both common and rare cardiovascular conditions with the promise of improved outcomes for patients worldwide.
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