World Heart Day 2025: Looking Back at Recent Progress in Cardiology Cell and Gene Therapy

Despite the great strides that have been made in recent years with small-molecule drugs and medical devices, significant unmet need remains in the field of cardiology, and cases of cardiac disease continue to rise both in the United States and in the European Union. In order to address this concern, some investigators, companies, and research institutions are now turning increased attention towards gene therapy and cell therapy as promising new modalities for treating cardiac diseases.

This year for World Heart Day, which is held annually on September 29, CGTLive® has collected some of key news stories from the past few months that highlight the ongoing progress in the field of gene and cell therapy for cardiovascular disease. Click the read more buttons for more details and information about each update.

FDA Lifts Clinical Hold on Rocket’s Trial for Danon Disease Gene Therapy RP-A501

August 21, 2025 — The FDA has lifted its clinical hold on Rocket Pharmaceuticals’ pivotal phase 2 clinical trial (NCT06092034) evaluating RP-A501, an investigational adeno-associated virus serotype 9 (AAV9) vector-based gene therapy intended to treat Danon disease.

The hold was originally placed on the trial by the FDA on May 23, 2025, following the death of a patient treated in the study. The patient’s death occurred after an acute systemic infection and was associated with an unexpected serious adverse event (SAE) of clinical complications related to a capillary leak syndrome. At the time the hold was announced, a comprehensive root cause analysis was underway, with a focus on a novel immune suppression agent specific to the AAV9 Danon program that had recently been added to the gene therapy’s pretreatment regimen with the intention of reducing complement activation, a phenomenon that had been seen in some participants. Rocket stated that dosing in the trial was paused when it became aware of the SAE.

With regard to the lifting of the hold, Rocket noted that the FDA indicated the company has addressed the issues leading to the clinical hold to its satisfaction. Per the FDA’s authorization for the study’s continuation, a recalibrated dose for the gene therapy, 3.8 x 10¹³ genomic copies/kg, will be used for the next 3 patients to be treated in the study and the patients will be treated in a sequential manner with intervals of 4 weeks or greater between each treatment. Notably, 6 patients have been treated in the phase 2 study so far and RP-A501 has previously been evaluated for Danon disease in a phase 1 clinical trial (NCT03882437).

BioCardia Reveals Plans to Request Meeting With FDA Regarding CardiAMP Heart Failure Cell Therapy

August 5, 2025 — BioCardia has stated that it plans to request a meeting with the FDA to discuss the pathway to approval for its CardiAMP cell therapy system, an investigational autologous cell therapy for the treatment of ischemic heart failure (HF).

The company noted that it plans to submit the meeting request by the fourth quarter of this year and that the meeting will focus on the approvability of the product based on available clinical data. CardiAMP is currently being evaluated in the pivotal phase 3 CardiAMP HF clinical trial (NCT02438306). Although the study did not meet its primary end points, BioCardia believes a number of factors may allow a pathway to approval for CardiAMP. The company cited as examples of these factors the breakthrough therapy designation previously granted to CardiAMP by the FDA, longer-term follow-up data from CardiAMP HF, the FDA’s prior 510(k) approval of Marrowstim, a primary component of CardiAMP cell therapy, and the confirmatory phase 3bCardiAMP HF II clinical trial (NCT06258447), which is currently enrolling patients at several sites in the United States. BioCardia also noted that is plans to submit a DeNovo 510(k) application for the Helix Transendocardial Delivery System (Helix) to the FDA in the third quarter of 2025. Helix is also a component of CardiAMP.

In addition to the updates regarding US regulatory activities, BioCardia also announced it expects that a clinical consultation with Japan’s Pharmaceuticals and Medical Devices Agency (PMDA), which the company requested in July of this year, will take place in the fourth quarter of 2025. BioCardia pointed out that if it and the agency are aligned during the meeting, it may be able to submit for market approval of CardiAMP in Japan.

Rocket’s PKP2-Arrhythmogenic Cardiomyopathy Gene Therapy RP-A601 Snags RMAT Designation

July 29, 2025 — Rocket Pharmaceuticals’ RP-A601, an investigational AAV vector-based gene therapy intended to treat plakophilin-2 related arrhythmogenic cardiomyopathy (PKP2-ACM), has received regenerative medicine advanced therapy (RMAT) designation from the FDA.

According to Rocket, the RMAT designation was granted based on results from a phase 1 clinical trial (NCT05885412) evaluating RP-A601. Notably, the gene therapy has previously received fast track designation and orphan drug designation (ODD) from the FDA and ODD from the European Commission.

“The FDA’s RMAT designation for RP-A601 represents a meaningful advancement for Rocket and for patients living with PKP2-ACM, a life-threatening genetic heart disease characterized by ventricular arrhythmias and sudden cardiac death,” Kinnari Patel, PharmD, MBA, the president and head of R&D at Rocket Pharmaceuticals, said in a statement. “This marks the fifth RMAT designation in our history and underscores our commitment to developing potentially curative gene therapies for patients with rare and inherited cardiovascular diseases. The early clinical data for RP-A601 are highly encouraging, and we look forward to continued collaboration with the FDA throughout the program’s development.”

Solid Biosciences' CPVT Gene Therapy SGT-501 Cleared for Phase 1b Trial

July 10, 2025 — Solid Biosciences' SGT-501, an investigational AAV vector-based gene therapy intended to treat catecholaminergic polymorphic ventricular tachycardia (CPVT), has received clearance of an investigational new drug (IND) application by the FDA and a clinical trial application by Health Canada.

In light of the clearances, the company plans to launch a phase 1b clinical trial in the final quarter of this year. SGT-501 is intended to address CPVT by providing a full-length, codon-optimized copy of the cardiac calsequestrin (CASQ2) gene to the muscle cells of the heart. Increase in the production of the CASQ2 protein is expected to stabilize the ryanodine receptor (RYR2) via improved buffering of free calcium in sarcoplasmic reticulum. According to Solid, stabilization of RYR2 is in turn expected to help maintain normal cardiac rhythm and may help protect patients from ventricular tachycardia.

“Despite being identified nearly 50 years ago, CPVT still lacks FDA-approved therapies – this announcement reflects a critical development in the treatment of this underserved, often fatal, cardiac disease,” Gabriel Brooks, MD, the chief medical officer of Solid, said in a statement.¹ “SGT-501 offers a precision genetic approach targeting the underlying pathophysiology of the disease: abnormal calcium releases from the sarcoplasmic reticulum in an otherwise structurally sound heart. We believe SGT-501 has the unique potential to provide durable protection and may be capable of liberating patients from the ever-present threat of lethal arrhythmias and life-limiting prohibitions on exercise. Solid is proud to launch this program to help address this clear unmet need, further expanding our pipeline of differentiated and thoughtfully designed genetic medicines.”

Nuevocor Snags IND Clearance for Gene Therapy Trial in LMNA DCM

June 11, 2025 — Singapore-based company Nuevocor has received clearance from the FDA for an IND application for NVC-001, an AAV vector-based gene therapy intended to treat LMNA-related dilated cardiomyopathy (LMNA DCM).

In light of the IND clearance, the company intends to go forward with plans for a first-in-human phase 1/2 ascending-dose clinical trial. Nuevocor expects to launch the 52-week trial, which will be open to adult patients, early next year. Participants in the trial will receive a 1-time dose of the gene therapy product via intravenous infusion.

LMNA DCM, which is found in approximately 100,000 people across the United States and Europe, is characterized by nuclear envelope disruption caused by mutations in LMNA, a gene necessary for nuclear envelope integrity. The condition results in heart muscle weakening, arrhythmias, and eventually end-stage heart failure.

REFERENCE
1. Hajjar R. The Quest to Overcome the Challenges in Cardiac Gene Therapy. Presented at: AHA Scientific Sessions 2023; November 10-13; Philadelphia, Pennsylvania. HF.EC.158