These, among many others, are some of the key clinical trials of gene, cell, and regenerative therapies that the CGTLive staff will be following throughout 2024.
As a clinical news source, CGTLive™ is constantly on the lookout for the latest information and data from the ongoing clinical development of novel gene and cell therapies for difficult-to-treat diseases, rare disorders, and other conditions.
Last year, we followed many trials closely to bring you all the updates as these treatments progressed through the pipeline toward a potential date with the FDA. This included various novel approaches to diseases without therapies, as well as newly approved treatments for areas in need of new options. These included major phase 2 and 3 clinical trial data readouts, including data only presented at some of the largest medical meetings in the world.
This year, we'll be similarly paying attention to the clinical pipeline to bring the most important updates for care directly to you, our audience. Although we'd love to include all of them, below we'll highlight just some of the trials we're looking forward to seeing data from in 2024.
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Treatment: Delandistrogene moxeparvovec
Delandistrogene moxeparvovec (Elevidys) was approved by the FDA for the treatment of Duchenne muscular dystrophy in June 2023, and the field is anticipating more data on Sarepta's agent. Also known as study SRP-9001-301, the EMBARK trial is anticipated to read out data sometime in 2024.
The study announced topline data in late 2023, showing that it failed to reach statistical significance in its key primary end point of change in North Star Ambulatory Assessment scores at week 52 compared to placebo. Key secondary end points—change in time to rise and 10-meter walk test—were statistically significant across all age groups, though.
Sponsor: Orca Biosystems
Orca-T, also known as TRGFT-201, is an Orca Biosystems’s candidate currently in a phase 3 trial which is anticipating its primary completion in April 2024. The treatment is an engineered allogeneic peripheral blood product that comprises purified donor-derived regulatory T-cell plus CD34 and hematopoietic progenitor cells.
Precision-T is investigating patients with advanced hematologic malignancies undergoing allogeneic hematopoietic cell transplantation with either TRGFT-201 with additional infusion of conventional T-cells and regulatory T-cells, or standard-of-care allogeneic graft.
After presenting positive topline data from the KARDIA-1 trial (NCT04936035) at the 2023 American Heart Association’s (AHA) Scientific Sessions, Alnylam's investigational RNA interference therapy is anticipated to read out more data from KARDIA-2 sometime in 2024.
Zilebesiran targets angiotensinogen, or AGT, a hormone produced predominantly in the liver that contributes to blood pressure regulation. KARDIA-1 randomized 394 participants with mild-to-moderate hypertension, and displayed a favorable safety profile. Alnylam has stated its plans to evaluate zilebesiran’s long-term safety and efficacy outcomes as the current findings are limited to the 6-month placebo-controlled period.
After opening trial sites in Europe, Canada, and Australia, the phase 2 ALPHA2 trial, which is assessing Allogene's CAR T-cell therapy ALLO-501A in relapsed/refractory large B-cell lymphoma, expects to complete enrollment in the first half of 2024. The therapy is CD19-targeted and designed to eliminate the rituximab recognition domains of its pipeline peer, ALLO-501, which could allow for use in a broader patient population.
Data from 33 patients who had not received CAR T-cell therapy previously and were treated with 1 of 2 planned infusions or consolidation therapy were announced in 2023, showing some durable responses with a manageable safety profile.
Sponsor: Marker Therapeutics
Previously known as MT-401, zelenoleucel is an investigational allogeneic MultiTAA T-cell therapy intended for the treatment of post-transplant acute myeloid leukemia. Marker Therapeutics received a grant from the FDA for the trial in 2022, which is set to be completed in July 2024.
ARTEMIS is a multicenter study with a safety lead-in evaluating the administration of zelenoluecel to patients who have received their first allogeneic hematopoietic stem cell transplantation. The dose administered is 50 x 106 cells.
Sponsor: Coeptis Therapeutics
Coeptis's allogeneic cell therapy candidate is designed to reduce relapse of graft vs host disease with universal donor ex-vivo expanded cord blood progenitor and hematopoietic stem cells. The trial is being conducted by Fred Hutchinson Cancer Center and is estimated to end in August 2024.
The phase 2 trial's primary end point is the incidence of graft failure up to day 45 post transplant, with additional assessments in patients between 10 and 65 years old. The Seattle-based cancer center sough to 15 patients in the study.
Sponsor: Iovance Biotherapeutics
LN-145 is a tumor-infiltrating lymphocyte therapy being evaluated in 2 trials of patients with advanced post non–small cell lung cancer. Iovance plans to enroll around 120 patients in the IOV-LUN-202 trial and is expecting to complete enrollment in the second half of 2024.
LN-145 is being assessed in 4 cohorts: patients with no PD-L1 tumor expression, with PD-L1 expression, regardless of expression and ineligible for resection, regardless of expression who elect to produce the autologous TIL cells before disease progression, and a retreatment group. The trial’s primary outcome measure is objective response rate.
AviadoBio has announced plans to expand clinical trial activities to the United States—activities it will initiate in 2024. The investigational adeno-associated virus vector-based gene therapy intended to treat frontotemporal dementia, or FTD, associated with progranulin (GRN) gene mutations, has received FDA clearance for its investigational new drug application and a fast track designation.
ASPIRE-FTD is an open-label, multicenter, ascending dose trial expected to treat 9 patients across 2 dose cohorts, with the gene therapy given via a 1-time administration to the thalamus by way of a minimally invasive stereotactic neurosurgical procedure. The company noted this approach is designed to allow for a lower dose of AVB-101 and to limit the potential for systemic exposure.
Sponsor: Gamida Cell
GDA-201 is a natural killer cell therapy that has displayed early evidence of antitumor activity in patients with relapsed/refractory B-cell non-Hodgkin lymphoma in a preliminary data read out in 2023. Gamida Cell anticipates that the full data set is anticipated to be announced in the first quarter of 2024.
The phase 1/2 trial is evaluating the allogeneic therapy for safety and tolerability in combination with rituximab after fludarabine or cyclophosphamide lymphodepletion, and consists of phase 1 dose-escalation and phase 2 dose-expansions parts and is enrolling patients with follicular (n = 1), diffuse/high-grade (n = 6), marginal zone (n = 2), and mantle zone B-cell lymphomas (n = 1).. GDA-201 was developed with the company;s proprietary nicotinamide technology.
Sponsor: Beam Therapeutics
Beam Therapeutics expects to announce initial data from its BEACON trial of BEAM-101, its autologous, base-edited CD34+ hematopoietic stem cell therapy, in sickle cell disease in 2024. The treatment is multiplexed base edited to avoid expression of the CD7, TRAC, PDCD1 and CD52 genesto reduce fratricide, graft-versus-host disease, and CAR-T cell exhaustion; as well as to evade anti-CD52 lymphodepleting agents and enable the use of an allogeneic cell source.
The trial is pursuing a total target of 45 treated patients in a multicenter, open-label evaluation of safety and efficacy in patients with relapsed/refractory T-cell acute lymphoblastic leukemia/T-cell lymphoblastic lymphoma. It is also seeking identification of the recommended phase 2 dose and lymphodepletion regimen. Key end points include adverse events, complete or partial responses, eligibility for hematopoietic stem cell transplant, and minimal residual disease negative status.
Sponsor: Cabaletta Bio
The investigational CD19-directed CAR T-cell therapy is designed to treat autoimmune diseases and was cleared for a clinical trial in generalized myasthenia gravis in 2023. At the time, Cabaletta's CEO noted that the company remains on track to deliver initial clinical data from CABA-201–treated patients with lupus and/or myositis in the first half of 2024.
The ongoing phase 1/2 trial in active systemic lupus erythematosus has an estimated enrollment of 12 patients, with a primary outcome measure of the incidence of adverse events and multiple secondary efficacy end points. The trial in idiopathic inflammatory myopathy sought to enroll 18 patients with a similar design for safety and efficacy measures.
Sponsor: Excision BioTherapeutics
The open-label, multicenter, phase 1/2 clinical trial has a planned enrollment of 9 male patients aged 18 years to 60 years with documented chronic HIV-1 infection and is anticipated to build upon data from the first 3 patients which were presented in October 2023. There was a planned dose escalation to the 3.0x1012 vg/kg dose shortly after, and more data are expected in 2024.
EBT-101 uses the CRISPR/Cas9 system, which was publicly validated with the FDA approval of Vertex Pharmaceuticals' and CRISPR Therapeutics’ exagamglogene autotemcel (marketed as Casgevy), which uses the same gene-editing mechanism.
Sponsor: Benetic Biopharma
BB-301 is a Benitec Biopharma adeno-associated virus (AAV) vector-based silence-and-replace gene therapy that is administered directly to the pharyngeal constrictor muscles. The trial is assessing the therapy as a treatment for oculopharyngeal muscular dystrophy (OPMD)-related dysphagia, and is expected to read out interim results sometime around the midpoint of 2024.
Benetic noted that the first patient dosed will be followed for 52 weeks going forward, with interim assessments of safety and efficacy planned every 90 days. For the clinical trial, the primary end point will be the safety of BB-301, and thus far, 19 patients are participating in the natural history study at a center in the United States, all of whom will be eligible to roll over into the clinical trial.
Sponsor: Atamyo Therapeutics
Atamyo's investigational AAV vector-based gene therapy is in development for the treatment of γ-sarcoglycan (SGCG)-related limb-girdle muscular dystrophy Type 2C/R5. It submitted a clinical trial application in late 2023 and expects the dosing of patients to begin in the first half of 2024
The trial is a multicenter, open-label, dose-escalation study evaluating safety, pharmacodynamic, efficacy, and immunogenicity of intravenous administration of ATA-200. In preclinical mouse models, ATA-200 demonstrated its tolerability and capability to correct symptoms and biomarkers of the pathology.
Sponsor: Lyell Immunopharma
In 2023, the FDA cleared Lyell Immunopharma’s investigational new drug application for LYL845, a tumor-infiltrating lymphocyte (TIL) therapy designed to treat relapsed/refractory melanoma, and the company announced a phase 1 trial. Screening began in the months following the application, and initial data are expected in 2024.
The open-label, dose-escalation trial will determine safety, tolerability, and a recommended phase 2 dose of LYL845. Secondary objectives will measure response rates, duration of response, progression-free survival, and overall survival. Another exploratory measure of T-cell stemness biomarkers will also be assessed.