Alicia Bigica

Patients treated with an investigational gene therapy to address severe leukocyte adhesion deficiency type 1 (LAD-I) showed impressive survival data and clinically significant reductions in hospitalizations and infections, according to findings presented at the 

2022 American Society of Gene and Cell Therapy Annual Meeting

As of the data cutoff for the phase 1/2 trial (NCT03812263), 7 of 9 patients dosed with the lentiviral gene therapy from Rocket Pharmaceuticals with at least 12 months of follow-up available had a 100% overall survival rate without allogeneic hematopoietic stem cell transplantation based on the Kaplan-Meier estimate post-infusion. In addition, all 9 treated patients have demonstrated statistically significant reductions in all-cause hospitalizations and severe infections, as well as resolution or improvement of all LAD-I-related skin abnormalities, including rashes and wound healing. 

In addition, no treatment-related serious adverse events were recorded, and all patients in the cohort have demonstrated sustained CD18 restoration and expression on more than 10% of neutrophils.

The gene therapy consists of autologous hematopoietic stem cells that are genetically modified with a lentiviral vector that contains a functional copy of the 

 gene, mutations in which cause deficiencies in beta-2 integrin. 

, primary investigator Donald B. Kohn, MD, distinguished professor of microbiology, immunology, molecular genetics, and pediatrics (hem/onc), and director, Human Gene Medicine Program at UCLA, detailed the exciting findings and his hope that the treatment will soon become available. Watch below:

1. Kohn DB, Sevilla J, Rao G, et al. 1188: Interim Results from an Ongoing Phase 1/2 Study of Lentiviral-Mediated Ex-Vivo Gene Therapy for Pediatric Patients with Severe Leukocyte Adhesion Deficiency-I (LAD-I). Presented at: 2022 American Socienty of Gene and Cell Therapy Annual Meeting. May 16-19, 2022; Washington, DC. 

2. Rocket Pharmaceuticals Presents Positive Top-line Data from Severe Leukocyte Adhesion Deficiency-I Program at the 25th Annual Meeting of the American Society of Gene and Cell Therapy (ASGCT). News release. Rocket Pharmaceuticals. May 19, 2022. https://ir.rocketpharma.com/news-releases/news-release-details/rocket-pharmaceuticals-presents-positive-top-line-data-severe 

Videos

In an interview with CGTLive, study primary investigator Donald Kohn, MD, discussed the safety and efficacy observed in the phase 2 trial. 

Gene Therapy for LAD-I Posts Impressive Survival Data

, taking place May 16-19, 2022 in Washington, DC, demonstrate good safety and promising efficacy for an investigational gene therapy to address refractory angina. 

The results, presented by Thomas Povsic, MD, PhD, professor of medicine and cardiology, Duke Clinical Research Institute, point to a clinically meaningful benefit for this patient population which has a high burden of disease. 

“We think this has the possibility of greatly impacting their quality of life and decreasing their resource utilization," Povsic, who is primary investigator on the EXACT trial, told 

The phase 1/2 clinical trial (NCT04125732) is examining epicardial administration of encoberminogene rezmadenovec (XC001), a replication-deficient adenoviral serotype 5 vector that expresses multiple isoforms of vascular endothelial growth factor (VEGF) including isoforms -121, -165, and -189. Twelve patients with refractory angina have been enrolled and underwent mini thoracotomy to recieve a one-time administration of the investigational therapy across 4 dose cohorts: 1x10

Notably, of the 17 serious adverse events recorded, none were related to the study drug. Three treatment-related AEs were reported in the high-dose group and included fever, fatigue, and lip swelling. At month 3 and through month 6, a dose-dependent effect was observed, with recorded improvements in mean total excercise duration of 0.6, 0.5, 1.1, and 2.0 minutes in cohorts 1 through 4, respectively. 

"This degree of improvement in exercise tolerance is associated with improvements in mortality," Povsic told CGTLive. "While these patients don’t suffer from a high rate of mortality, it's important to realize this improvement in exercise tolerance is really clinically significant.”

Based on the findings, the phase 2 dose-expansion portion of the study will move forward at the highest dose. 

Watch our interview below for more details about the findings. 

Povsic TJ, Traverse JH, Henry TD, et al. Preliminary Safety, Tolerability and Efficacy of Direct Epicardial Administration of Encoberminogene Rezmadenovec to Ischemic Myocardium in Patients with Refractory Angina: Six Month Phase 1 Data. Presented at: 2022 American Society of Gene and Cell Therapy Annual Meeting; May 16-19, 2022; Washington, DC.

Safety and efficacy data suggest this to be a feasible and clinically meaningful treatment for a patient population with high disease burden. 

Gene Therapy for Refractory Angina Promotes Increased Exercise Tolerance

New data from the ongoing Imagine-1 clinical trial (NCT04713475) demonstrate good safety and impressive improvements in clinically meaningful end points in patients with GM1 gangliosidosis treated with PBGM01, an investigational gene therapy from Passage Bio. 

A single, intra cisterna magna administration of the adeno-associated viral vector serotype Hu68-based therapy, which delivers a functional copy of the human galactosidase beta 1 gene (

) to the cerebrospinal fluid, resulted in documented improvements across all developmental areas, including motor, language, and fine motor skills, in 2 patients with late-onset GM1 in who received the low-dose (3.3 x 10

The findings were presented by David Weinstein, MD, MMSc, senior vice president, clinical development, Passage Bio, during a late breaker session at the 

, taking place May 16-19, 2022 in Washington, DC.

"Ultimately, we're going to be judged based upon whether we can help these children developmentally, and I'm thrilled to share that the children are making very exciting advances," Weinstein told 

Weinstein reported up to 13 and 7 months of follow-up from patient 1 and 2, respectively. As of the data cutoff, no serious adverse events have been reported, and all possibly treatment-related AEs were grade 1, and grade 2 events were deemed unrelated to treatment. No evidence of liver or dorsal root ganglion toxicity have been observed. 

Notably, Patient 1, who was 15 months old at time of treatment, gained 12 months developmentally on the Vineland Adaptive Behavior Scale-II over the first 12 months of follow-up, reaching 24 months of developmental milestones. Weinstein reported that the patient is now running, jumping, showing good fine motor skills, and is forming basic sentences. 

Patient 2, who was diagnosed later in the disease course at 30 months of age and had demonstrated regression in motor and language skills prior to study enrollment, has advanced 6 months on the Vineland Scale over 7 months of follow-up, and has regained some of the skills lost, including language skills, post-treatment.  

In addition, volumetric MRI data from Patient 1 has demonstrated an increase in brain volume at 12-month follow-up compared with baseline, in line with expected development for children ages 0 to 24 months. Notably, the second patient, who was dosed at age 31 months, did not experience this brain volume growth, with a slight decline recorded at 6-month follow-up. 

"The fact that we haven't seen the same growth may be due to the child being older. More studies are needed to determine if age or disease severity are going to be important [moving forward]," Weinstein said. 

Weinstein D, Hastings CA, Day-Salvatore DL, et al. Interim Safety, Biomarker, and Efficacy Data From Imagine-1: A Phase 1/2 Open-label, Multicenter Study to Assess the Safety, Tolerability, and Efficacy of a Single Dose, ICM Administration of PBGM01 in Subjects with Type I (Early Onset) and 10. Type IIa (Late Onset) Infantile GM1 Gangliosidosis (GM1). Presented at: 2022 American Society of Gene and Cell Therapy Annual Meeting; May 16-19, 2022; Washington, DC. 

Data from 2 patients dosed in the Imagine-1 clinical trial were presented in a late breaking session at ASGCT 2022. 

Improvements in Developmental Milestones Observed With GM1 Gangliosidosis Gene Therapy

One-year data from an early phase clinical trial (NCT03362502) in ambulatory patients with Duchenne muscular dystrophy (DMD) showed acceptable safety and good, increasing expression of mini-dystrophin, with trends toward functional improvement following treatment with fordadistrogenemovaparvovec (Pfizer).

The findings were presented by Russell J. Butterfield, MD, of the University of Utah School of Medicine, at the 

The investigational gene replacement therapy was previously the subject of a clinical hold placed by the FDA following a fatal serious adverse event in a nonambulatory participant in December 2021. Following the event, THE FDA completed data and protocol amendment reviews and received more information from Pfizer regarding the potency assay.

The clinical hold on the investigational new drug application 

 in late April 2022, paving the way for Pfizer to restart its global phase 3 clinical trial (CIFFREO; NCT04281485) of the treatment now with a protocol amendment that includes a 7-day hospitalization period for close monitoring following administration of the therapy.

Among the ambulatory cohort in the phase 1b trial, 19 participants (median age, 8.8 years) with a baseline median North Star Ambulatory Assessment (NSAA) total score of 27 who were on a stable, daily corticosteroid regimen received a single intravenous infusion of fordadistrogenemovaparvovec (n=3 low-dose; n=16 high-dose).

Three treatment-related adverse events were reported: dehydration, acute kidney injury, and thrombocytopenia, all of which resolved within 15 days. Among those in the high-dose group, mean dystrophin/mini-dystrophin levels were 22% and 40% of normal at 2 and 12-month follow-up, respectively, as measured by liquid chromatography-mass spectrometry. In addition, dystrophin-positive fibers, as measured with immunofluorescence, were 39% and 62% at 2 and 12 months follow-up.

Compared with an external placebo cohort (N=66), who were matched in age, weight, baseline function, and steroid use, a trend towards functional improvement was observed at 1-year post-dosing, including a median 1-point improvement on NSAA compared with a 4-point decline in the control group (

 <.005). Other functional end point observations were a median 1-point decline in the treatment group compared with a 23-point decline in the control group on 6 minute walking distance; .02 decline in 4 stair climb velocity compared with a .06 decline in controls; and a median 6-point improvement in percent predicted forced vital capacity in the treatment group compared with a 1.4-point decline in controls.

The findings support the advancement of the program into phase 3, for which Pfizer recently announced that it plans to open its US sites, in line with the go-ahead received from other regulatory authorities in the United Kingdom, Canada, Taiwan, Spain, and Belgium, with nearly all sites of the CIFFREO clinical trial open by the end of June 2022.

1. Butterfield RJ, Shieh PB, Yong F, et al. Results of One Year Follow-Up After Treatment WithFordadistrogeneMovaparvovec (PF-06939926) for Duchenne Muscular Dystrophy (DMD) in A Phase 1b, Open-label Study. Presented at: 2022 American Society of Gene and Cell Therapy Annual Meeting; May 16-19, 2022; Washington, DC. LB 8.

2. Pfizer to Open First U.S. Sites in Phase 3 Trial of Investigational Gene Therapy for Ambulatory Patients with Duchenne Muscular Dystrophy. Pfizer news release. April 28, 2022. Accessed April 28, 2022. 

https://www.pfizer.com/news/press-release/press-release-detail/pfizer-open-first-us-sites-phase-3-trial-investigational

Articles

Study sponsor Pfizer recently announced the launch of a phase 3 trial in patients with Duchenne muscular dystrophy.  

Improved Function Observed Following Mini-Dystrophin Gene Therapy in DMD 

Editas Medicine has announced that the FDA has granted orphan drug designation to EDIT-301, its investigational gene-edited cell therapy which is currently being evaluated in severe sickle cell disease, with a phase 1/2 trial in transfusion-dependent 

“Receiving orphan drug designation for EDIT-301 for beta thalassemia highlights the urgent need for new treatment options for patients,” said James C. Mullen, chairman, president, and chief executive officer, Editas Medicine, in a statement. “Preparations to initiate the Phase 1/2 clinical trial of EDIT-301, a potentially transformative medicine for people living with beta thalassemia, are underway, and we look forward to dosing the first patient in the clinical trial this year.”

The FDA previously granted EDIT-301 rare pediatric disease designation for both beta thalassemia and sickle cell disease.

The one-time treatment consists of autologous CD34+ hematopoietic stem and progenitor cells that are edited at the gamma globin gene (HBG1, HBG2) promoters via a specific and proprietary engineered AsCas12a nuclease. Therapy-derived red blood cells in turn produce a sustained increase in fetal hemoglobin.

The ongoing phase 1/2 RUBY trial (NCT04853576) is evaluating the safety, tolerability, and efficacy of a single dose unit of EDIT-301 in adults age 18 to 50 with severe sickle cell disease. Up to 40 participants will receive a 1-time intravenous infusion after undergoing myeloablative conditioning with busulfan.

The primary end point is difference in rates of severe vaso-occlusive events (VOE) that require medical attention, as measured over 2 years post-infusion. Secondary end points include the proportion of participants with mean fetal hemoglobin (HbF) >20% compared with baseline and mean Hb ≥10 g/dL starting at least 60 days after last packed red blood cell transfusion compared with baseline, both up to 2 years post-infusion. Additional secondar outcomes include annual number of packed red blood cell transfused for sickle cell-related events; change from baseline in annualized rate of hospitalization for severe VOEs; change from baseline in rates of severe VOEs by at least 75% and 90%; and complete resolution of severe VOEs, all evaluated up to 2 years post-infusion.

Editas Medicine Receives FDA Orphan Drug Designation For EDIT-301 For The Treatment Of Beta Thalassemia. News release. Editas Medicine. May 12, 2022. 

https://ir.editasmedicine.com/news-releases/news-release-details/editas-medicine-receives-fda-orphan-drug-designation-edit-301

The investigational therapy is also currently being evaluated in a clinical trial for sickle cell disease.  

Editas’ Gene-Edited Cell Therapy for Beta Thalassemia Wins Orphan Status 

CB-010, an allogeneic chimeric antigen receptor (CAR) T cell therapy in development by Caribou Biosciences, produced a 100% overall response rate (ORR) in all 5 patients with relapsed or refractory B cell non-Hodgkin lymphoma (r/r B-NHL) who received the therapy in the ANTLER phase 1 trial (NCT04637763).

The company announced initial results in a statement

 ahead of a presentation at the upcoming European Hematology Association (EHA) 2022 Hybrid Congress, being held in Vienna, Austria, June 9-17, 2022.

“Our initial CB-010 data are exciting, and we believe these results show the potential to set a new therapeutic bar in treating patients with aggressive r/r B-NHL. These excellent initial outcomes represent important steps toward validating our chRDNA genome-editing platform as well as our plans for future development of CB-010 and our broader pipeline,” Rachel Haurwitz, PhD, Caribou’s president and chief executive officer, said in the statement.

The ANTLER trial is evaluating the safety, tolerability, and efficacy of CB-010, an allogeneic anti-CD19 CRISPR-edited CAR T-cell therapy that is engineered to knock out PD-1, intended to help improve antitumor activity. The 2-part trial consists of a dose escalation phase that follows at 3+3 design, followed by a dose expansion phase in which participants will receive the dose indicated in phase 1. The primary end points are number of dose-limiting toxicities over 28 days post-infusion and tumor response, as measured by objective response rate, over 12 months. The study plans to enroll up to 50 participants.

The current data account for 6 patients with r/r B-NHL with a history of a median of 3 prior therapies who were administered CB-010 at dose level 1 (40x10

 CAR-T cells) following a lymphodepletion regimen of cyclophosphamide at 60 mg/kg/d for 2 days followed by fludarabine at 25 mg/m2/d for 5 days. As of the cutoff date, all 6 patients had been treated and 5 had completed 28-day follow-up.

At that point, 4 patients achieved a complete response and 1 achieved a partial response. Notably, all 4 patients who had a complete response sustained that response at 3 months, with the longest recorded complete response as of the data cutoff being 6 months.

In terms of safety, no cases of graft versus host disease were reported, with 3 of 6 patients developing grade 3 or 4 adverse events within the 28-day follow-up period, including neutropenia (50%), thrombocytopenia (33%), anemia (17%), and hypogammaglobulinemia (17%). One patient experienced grade 1 cytokine release syndrome and grade 3 immune effector cell-associated neurotoxicity syndrome, a dose-limiting toxicity. The patient received treatment and recovered within 39 hours, going on to achieve a complete response.

Based on these data, trial investigators are now enrolling the second cohort of patients at dose level 2 (80x10

“We are slated to present additional ANTLER interim data at EHA next month and expect more data by year end as we continue to advance our lead program. Our overarching goal is to develop CB-010 such that it will meaningfully rival autologous cell therapies to reach broader groups of patients globally who are in need of off the shelf treatments,” Haurwitz said.

Caribou Biosciences announces positive initial data for cb-010 anti-cd19 allogeneic car-t cell therapy. News release. Caribou Biosciences. May 12, 2022. 

https://investor.cariboubio.com/news-releases/news-release-details/caribou-biosciences-announces-positive-initial-data-cb-010-anti

Caribou will present the initial data at the upcoming European Hematology Association (EHA) meeting in June. 

Caribou’s CRISPR-Edited CAR T-Cell Therapy CB-010 Elicits Complete Response in R/R B-NHL

Interim data from Cartesian Therapeutics’ phase 1/2a clinical trial evaluating its autologous CAR T-cell therapy Descartes-08 in patients with myasthenia gravis showed good safety and promising efficacy.

The findings were presented as late-breaking data at the 14th Myasthenia Gravis Foundation of America (MGFA) International Conference on Myasthenia and Related Disorders, taking place in Miami, Florida May 10-12, 2022.

The 2-part, ongoing phase 1/2a clinical trial (NCT 04146051) includes dose escalation and dose expansion phases assessing safety, feasibility, and preliminary efficacy of Descartes-08, autologous, RNA-modified T-cells that express a chimeric antigen receptor directed to B-cell maturation antigen (BCMA) in up to 18 participants with generalized myasthenia gravis.

In the dose escalation part of the study, 3 ascending doses were administered to 3 participants with severe, treatment-refractory myasthenia gravis. Data showed that the therapy was generally well-tolerated, with no reports of cytokine release syndrome or other treatment-related adverse events. Of note, participants experienced at least 1 full class of improvement in MGFA clinical classification, as well as over a 50% mean improvement on the Myasthenia Gravis Composite (MGC) Scale 3 months post-infusion with Descartes-08.

In the dose expansion phase, Cartesian presented data on 2 patients who have thus far been dosed as part of the weekly dosing cohort and have received all 6 infusions and completed 10-week follow-up. Overall, the cell therapy was well-tolerated, and both patients, who had severe disease at baseline (MGC >22) experienced significant improvements in disease severity, with MGC score improvements at 10 weeks from 27 to 2 in patient 1 and from 23 to 3 in patient 2.

"I am very encouraged by the interim analysis findings for this RNA CAR T-Cell therapy," said principal investigator Volkan Granit, MD, in a statement. "The treatment appears safe and well tolerated, and the extent of clinical improvement seen in our early participants is remarkable. If future data in a controlled study corroborate these findings, Descartes-08 would become a welcome addition to our armamentarium for treating MG."

In addition to myasthenia gravis, Descartes-08 is also being studied in an ongoing phase 2a clinical trial (NCT04816526) as a potential frontline therapeutic for multiple myeloma.

Cartesian Therapeutics to Present Late-Breaking Data from Phase 1/2a Trial of RNA CAR T-cell Therapy in Patients with Generalized Myasthenia Gravis. News release. Cartesian Therapeutics. May 10, 2022. 

https://www.prnewswire.com/news-releases/cartesian-therapeutics-to-present-late-breaking-data-from-phase-12a-trial-of-rna-car-t-cell-therapy-in-patients-with-generalized-myasthenia-gravis-301543090.html

Late-breaking interim data were presented at the 14th Myasthenia Gravis Foundation of America (MGFA) International Conference on Myasthenia and Related Disorders.

RNA CAR T-Cell Therapy for Myasthenia Gravis Shows Benefits in Early Results 

Biotechnology company Arcellx announced that it has dosed its first patient in the phase 1, open-label clinical trial of ACLX-001, a CAR T-cell therapy born out of the firm’s ARC-SparX cell therapy platform that will be evaluated in patients with relapsed or refractory multiple myeloma (r/r MM).

The universal ARC-SparX cell therapy platform is comprised of soluble protein antigen-receptor X-linkers (SparX) proteins that are engineered to target BCMA on myeloma cells. This works in conjunction with antigen-receptor complex-T (ARC-T) cells that are separately dosed and only active when engaged with a SparX protein that is bound to a myeloma cell. These cells and proteins utilize Arcellx’s novel synthetic binding scaffold, D-Domain, which can potentially enable higher transduction efficiency, high cell surface expression, and low tonic signaling.

The phase 1, proof of concept, dose-escalation study 

 will assess up to 65 participants in 2 treatment arms: (1) CART-ddBCMA and (2) SPRX001 and ARC-T cells. Based on pharmacokinetic data, a matrix escalation of either ARC-T cells, SparX-001, or both may be escalated during the trial. Primary outcomes are incidence of treatment-emergent adverse events, including dose-limiting toxicity, and determination of the recommended phase 2 dose over 24 months of follow-up. Secondary outcomes, also assessed over 24 months, are best overall response based on International Myeloma Working Group (IMWG) Consensus Criteria, IMWG-based objective response rate, and in vivo expansion and persistence of the investigational agent in peripheral blood and target tissues.

"ARC-SparX provides physicians with the ability to control the dose and frequency of SparX administration. This may allow the physician to better manage toxicities associated with traditional CAR-T therapies, potentially increasing patient access to this treatment option,” said Binod Dhakal, MD, MS, trial investigator and associate professor of medicine, Division of Hematology/Oncology, Medical College of Wisconsin.

In addition to ACLX-001, Arcellx is also planning to assess another ARC-SparX program—ACLX-002—in a phase 1 program in r/r acute myeloid leukemia and high-risk myelodysplastic syndrome in the second half of 2022.

The company also recently published results from its phase 1 study on its lead program, CART-ddBCMA, which demonstrated a 100% overall response rate and nearly 70% complete response rate in patients with r/r MM.

, Arcellx chairman and CEO Rami Elghandour said “When you transduce your cells using a viral vector to produce a CAR T therapy, a higher percentage of our cells are CAR-positive, or, in effect, they would be tumor-identifying and killing. As a result of having that higher transduction efficiency, we can, in effect, have a lower overall total cell dose, which we believe can contribute to having a therapy that is both effective and more tolerated, or the potential for a better safety profile."

"These are obviously early results but they're very encouraging results," he continued. "We have an upcoming presentation at the ASCO meeting in June where we're excited to show further results."

1. Arcellx Announces Dosing of First Patient in its Phase 1 Clinical Trial Evaluating ACLX-001, the First Therapeutic in the Dosable and Controllable ARC-SparX Platform, for the treatment of Patients with Relapsed or Refractory Multiple Myeloma. News release. Arcellx. May 10, 2022. 

https://www.prnewswire.com/news-releases/arcellx-announces-dosing-of-first-patient-in-its-phase-1-clinical-trial-evaluating-aclx-001-the-first-therapeutic-in-the-dosable-and-controllable-arc-sparx-platform-for-the-treatment-of-patients-with-relapsed-or-refractory-multi-301544169.html

2. Frigault MJ, Bishop MR, Rosenblatt J, et al. Phase 1 Study of CART-ddBCMA for the treatment of subjects with relapsed and refractory multiple myeloma [published online ahead of print]. 

The cell therapy is the first to come out of the company’s proprietary ARC-SparX platform.

Arcellx Doses First Patient in ARC-SparX CAR-T Program for Multiple Myeloma 

During its Q1 earnings call, REGENXBIO disclosed that it uncovered an “unexpected and isolated observation” during the vial-filling stage of the manufacturing process for its Duchenne muscular dystrophy 

 at a third-party manufacturing facility.

The discovery will disrupt the initiation of patient dosing in the first in human phase 1/2 AFFINITY DUCHENNE clinical trial of RGX-202. The gene therapy, which utilizes the company’s proprietary NAV AAV8 vector to deliver a novel microdystrophin transgene that includes the functional elements of the C-Terminal domain found in naturally occurring dystrophin, has demonstrated evidence of microdystrophin protein expression in muscles in preclinical studies.

“Though we made the difficult decision to delay dosing patients in our RGX-202 trial, we continue to prepare for trial initiation,” Kenneth T. Mills, president and chief executive officer of REGENXBIO, said in a statement.

Following its investigational new drug application approval in January 2022,

 the company planned to initiate the trial in the first half of this year. Now, due to the manufacturing issue, REGENXBIO says that dosing will likely take place in early 2023.

The unfortunate discovery comes as the company also announced that its in-house manufacturing facility—which it intended to use for future manufacturing of RGX-202—is now operational and allows for the high-yield production of NAV vectors at up to 2000 liters using the company’s platform suspension cell culture process.

The phase 1/2 AFFINITY DUCHENNE trial is a multicenter, open-label, dose escalation and dose expansion study set to evaluate the safety, tolerability, and efficacy of a one-time intravenous dose of RGX-202 in patients with Duchenne muscular dystrophy.

The trial plans to enroll 6 ambulatory pediatric patients in 2 dosing cohorts: 1x10

 genome copies (GC)/kg body weight (n=3) and 2x10

 GC/kg body weight (n=3). Up to 6 additional patients may be added in each cohort during the dose expansion phase pending review by an independent safety data monitoring board. Safety measures, including inclusion criteria that includes patients with DMD gene mutations between exons 18 and 58 and a short-term immunosuppression regimen in order to mitigate risk of immunologic response, will be employed.

Trial end points include safety, microdystrophin protein levels in muscle, immunogenicity assessments, and strength and functional assessments, including the North Star Ambulatory Assessment and timed function tests.

1. REGENXBIO reports first quarter 2022 financial results and recent operational highlights. News release. REGENXBIO. May 4, 2022. 

https://regenxbio.gcs-web.com/news-releases/news-release-details/regenxbio-reports-first-quarter-2022-financial-results-and

2. REGENXBIO announces FDA clearance of IND for clinical trial of RGX-202, a novel gene therapy candidate for Duchenne muscular dystrophy. News release. REGENXBIO. January 6, 2022. 

https://regenxbio.gcs-web.com/news-releases/news-release-details/regenxbio-announces-fda-clearance-ind-clinical-trial-rgx-202

The trial was set to begin patient dosing in the first half of this year. 

REGENXBIO DMD Gene Therapy Trial Delayed Due to Manufacturing Issue

Findings from the ongoing PERCEIVE study demonstrate continued safety and efficacy of voretigene neparvovec (Luxturna; Spark Therapeutics) in patients with 

-mediated inherited retinal dystrophy in the real-world setting.

The findings, which included up to 2 years of data and were presented at the Association for Research in Vision and Ophthalmology (ARVO) 2022 Annual Meeting, also shed light on a new treatment-related adverse reaction.

 and the European Commission in 2018, voretigene neparvovec was the first directly administered adeno-associated virus gene therapy to gain approval and the first approved ocular gene therapy. Intended to treat children and adults with confirmed biallelic 

 mutation-associated retinal dystrophy that leads to vision loss and blindness, the therapy delivers a functional copy of the 

 gene directly to retinal cells to restore normal protein production, ultimately restoring a patient’s vision.

The therapy’s safety and efficacy was established in 2 phase 1 clinical trials and an open-label, randomized phase 3 trial,

 in which a statistically significant and clinically meaningful difference was observed in the primary end point, mean bilateral multi-luminance mobility testing score change, between the intervention group (n=21) and control group (n=10) at 1 year (difference of 1.6; 95% CI, 0.72, 2.41; 

 = .001). In addition, a statistically significant difference in 2 key secondary end points were observed, including full-field light sensitivity threshold testing averaged over both eyes (

 = .001) and the mobility test score change for the first injected eye (

 = .001). A third secondary endpoint, change in visual acuity averaged over both eyes, was not statistically significant between the groups.

Launched in 2019, the post-marketing PERCEIVE trial follows patients for up to 5 years. As of the August 2021 data cutoff, 106 patients were enrolled and 103 received treatment with the gene therapy (mean age, 19.5 years; 50.5% female; mean duration of follow-up, 0.8 years [max, 2.3 years]). Among the group, 35% experienced at least 1 ocular adverse event (AE), including 13 instances of chorioretinal atrophic changes at the injection site or elsewhere, which were the most common AE.

Ocular AEs of special interest included foveal degeneration (n = 4), vitritis (n = 4), eye inflammation (n = 3), retinal tear (n = 2), and increased intraocular pressure (n = 5). Two serious AEs, eye inflammation and increased intraocular pressure, were reported by 1 patient each. The most frequent nonocular AE was headache. Notably, 1 patient with no prior history of mental illness, reported 3 instances of a psychiatric disorder.

In terms of efficacy, visual function improved in terms of full-field light sensitivity threshold,and best-corrected visual acuity (LogMAR) at year 2 with a mean change from baseline of −13.67 decibels and −0.03, respectively.

“Overall, the safety and effectiveness of [voretigeneneparvovec] observed in the PERCEIVE study, with up to 2-years data, are consistent with the findings of [voretigeneneparvovec] clinical trials,” the investigators concluded.

1. Fischer MD, Maier R, Suhner A, et al. PERCEIVE study report: Real-world safety and effectiveness of voretigeneneparvovec. Presented at: Association for Research in Vision and Ophthalmology (ARVO) 2022 Annual Meeting. May 1-4, 2022; Denver, CO.

2. FDA approves novel gene therapy to treat patients with a rare form of inherited vision loss. News release. US FDA. December 17, 2018. https://www.fda.gov/news-events/press-announcements/fda-approves-novel-gene-therapy-treat-patients-rare-form-inherited-vision-loss#:~:text=The%20U.S.%20Food%20and%20Drug,that%20may%20result%20in%20blindness

3. Russell S, Bennett J, Wellman JA, et al. Efficacy and safety of voretigeneneparvovec (AAV2-hRPE65v2) in patients with RPE65 -mediated inherited retinal dystrophy: a randomised, controlled, open-label, phase 3 trial. 

2017;390(10097):849-860. doi:10.1016/S0140-6736(17)31868-8

Investigators presented up to 2 years of post-marketing data on the first-ever gene therapy.