World Heart Day 2024: Looking Back at Cardiology's Year of Progress in Cell and Gene Therapy
In observance of World Heart Day, held annually on September 29, we took a look back at the past year's news in cell/gene therapy for cardiovascular disease.
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.
In light of World Heart Day, observed annually on September 29 by the patient and clinician communities, CGTLive® has taken a look back at the past year's progress in cardiology gene therapy and cell therapy. Click the read more buttons for more details and information about each update.
Rocket Pharmaceuticals Maxes Out Recruitment in Pivotal Trial for Danon Disease Gene Therapy RP-A501
September 19, 2024 — Rocket Pharmaceuticals has finished enrolling all patients in a pivotal phase 2 clinical trial (NCT06092034) evaluating RP-A501, an investigational adeno-associated virus (AAV) vector-based gene therapy, for the treatment of Danon disease.
The single-arm trial enrolled 12 male patients in total across the United States and European Union, and all patients received a dose of 6.7x1013 GC/kg of the gene therapy. The first 2 patients were enrolled as part of a pediatric safety run-in, which utilized sequential enrollment and required at least 3 months of follow-up before further recruitment. Improvements in expression of LAMP2, the disease-targeted protein, serves as 1 of 2 primary end points for the study, alongside the observed decrease in left ventricular mass. Among the study’s secondary end points are a key secondary end point for the change in troponin levels and additional end points for natriuretic peptide levels, event free survival up to 24 months, treatment-emergent safety events, New York Heart Association (NYHA) class, and responses on the Kansas City Cardiomyopathy Questionnaire. The results will be compared to findings from a global natural history study that the company is carrying outsimultaneously. Rocket stated that it intends to seek regulatory filings for RP-A501 inside and outside the US concurrently.
“From a clinical perspective, the important thing is that we are moving closer to the goal of having a treatment for patients with Danon disease,” Barry H. Greenberg, MD, FHFSA, the director of the Advanced Heart Failure Treatment Program and a distinguished professor of medicine at UC San Diego Health, said in a statement. “I can attest to the excitement and anticipation within the Danon patient community for this novel, one-time treatment designed to improve cardiac abnormalities associated with Danon disease and help preserve normal cardiac function by delivering functional LAMP2B genes to the heart tissue. The rapid recruitment of the phase 2 trial signifies the positive views of the study clinicians regarding this investigational therapy.”
Gene Therapy Improves Some Disease Biomarkers of Friedreich Ataxia Cardiomyopathy
July 15, 2024 — LX2006 gene therapy (Lexeo Therapeutics) improved some disease biomarkers in treated patients with Friedreich Ataxia (FA) cardiomyopathy, according to interim data from the Lexeo SUNRISE-FA Phase 1/2 clinical trial (NCT05445323) and the Weill Cornell Medicine investigator-initiated phase 1A trial (NCT05302271) evaluating the therapy.
LX2006 is an AAV vector gene therapy designed to deliver a functional frataxin gene to promote frataxin protein expression and restore mitochondrial function in myocardial cells.
“We're particularly excited by the potential of gene therapies to address rare conditions. We're doing active research that is funded by NIH, focused on FA, which is a rare condition that can affect both the neurologic system as well as the cardiovascular system. And in fact, cardiovascular clauses are a leading cause of death in that patient population,” Jonathan W. Weinsaft, MD, chief of cardiology and professor of medicine at Weill Cornell Medical College, told CGTLive.
First Patient in US Trial Receives Nexcella’s Light Chain Amyloidosis CAR-T NXC-201
July 11, 2024 — Immix Biopharma has dosed the first patient in the phase 1b/2 NEXICART-2 clinical trial (NCT06097832), the first trial in the United States evaluating subsidiary Nexcella's NXC-201 (formerly referred to as HBI0101), an investigational autologous chimeric antigen receptor T-cell (CAR-T) therapy that targets B-cell maturation antigen (BCMA), for the treatment of relapsed/refractory (r/r) light chain (AL) amyloidosis.
The open-label, single-arm, multisite NEXICART-2 study will aim to enroll around 40 participants in total. It will begin by treating 3 patients at a dose of 150x106 CAR+T cells and 3 patients at 450x106 CAR+T cells; pending safety results in these groups, some participants may later receive a dose of 800x106 CAR+T cells. Complete response rate and overall response rate will constitute the primary end points for NEXICART-2. Participants in the study will be required to have adequate cardiac function and to have not previously received a BCMA-targeted therapy. The first patient was dosed at Memorial Sloan Kettering Cancer Center (MSKCC), the trial’s lead site.
“I am excited to initiate the only CAR-T clinical trial currently recruiting for AL Amyloidosis patients that have progressed on front-line daratumumab (Darzalex)-combination therapy,” Heather Landau, MD, the MSKCC Amyloidosis Program director and the NEXICART-2 principal study investigator, said in a statement. “A 1-time therapy such as NXC-201 would provide an attractive option for AL Amyloidosis patients and clinicians. There are no approved drugs for relapsed/refractory AL Amyloidosis today.”
Verve Therapeutics Doses First Patient in Phase 1b Trial for Gene Therapy VERVE-102
May 14, 2024 — Verve Therapeutics has dosed the first patient in Heart-2, a phase 1b clinical trial (NCT06164730) evaluating VERVE-102, an investigational in vivo base editing therapy that uses a lipid nanoparticle (LNP) delivery system, for the treatment of heterozygous familial hypercholesterolemia (HeFH) or premature coronary artery disease (CAD).
VERVE-102 is intended to lower levels of low-density lipoprotein cholesterol (LDL-C), which drives disease symptoms in the aforementioned indications, by permanently inactivating the PCSK9 gene in the cells of the liver. The gene editing product, which is intended to serve as a one-time treatment, targets PCSK9 with the use of an optimized guide RNA and delivers mRNA coding for an adenine base editor. Furthermore, it is directed to the cells of the liver via a GalNAc-LNP delivery technology
The open-label, single-ascending dose study is recruiting adult patients who need additional lowering of LDL-C, and will assess outcomes by measuring pharmacokinetics and changes in levels of the PCSK9 protein and LDL-C in the blood. Four dose cohorts, which will each include 3 to 9 patients with either eligible disease, are planned.
Sardocor’s Heart Failure Gene Therapy SRD-001 Garners Fast Track Designation as First Patients Are Dosed
February 15, 2024 — Medera subsidiary Sardocor’s SRD-001, an investigational AAV vector-based gene therapy being evaluated for the treatment of Heart failure with preserved ejection fraction (HFpEF) in the phase 1/2a MUSIC-HFpEF clinical trial (NCT06061549), has been granted fast track designation by the FDA. In addition, the first 3 participants in the trial have now been dosed with the gene therapy.
SRD-001 is directly delivered to cardiac ventricular muscle cells by use of Sardocor’s proprietary intracoronary infusion system that is designed to increase the protein expression and functional activity of SERCA2a. In preclinical research conducted with Medera subsidiary Novoheart’s bioengineered HFpEF Human mini-Heart models, downregulated SERCA2a protein levels were implicated as the key factor in disease-associated calcium-handling defects. SRD-001 is expected to improve relaxation defects in HFpEF via overexpression of SERCA2a protein. Sardocor’s intracoronary infusion system allows for lessened dependence on tropism and for viral titers less than 1/100-fold per patient than seen in other conventional methods of administering gene therapy; this is expected to reduce or eliminate some potential adverse events while still allowing for efficient transduction.
“The enrollment of the first patients in this gene therapy trial will serve to validate the large body of work that has implicated deficiency of calcium cycling in HFpEF”, Roger Hajjar, MD, cofounder of Medera and Sardocor and the director of the Mass General Brigham Gene and Cell Therapy Institute, said in a statement.
