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Back to the Future: How New and Emerging Trends in CAR T-Cell Therapy Can Affect Your Patients

Patient use of the 2 FDA-approved gene therapy products for sickle cell disease (SCD), Vertex Pharmaceuticals' and CRISPR Therapeutics’ 

 (exa-cel; marketed as Casgevy) and bluebird bio’s 

 (lovo-cel; marketed as Lyfgenia), in the commercial setting has remained low.

Despite the approval of both gene therapy products by the FDA occurring simultaneously on December 8, 2023, only 4 patients have begun treatment with lovo-cel in the commercial setting, while 20 patients are reported to have begun treatment with exa-cel. Alongside the number for lovo-cel, bluebird also pointed out that this year 4 patients have started on elivaldogene autotemcel (Lenti-D, Skysona), its marketed gene therapy for cerebral adrenoleukodystrophy, and 19 patients have started on betibeglogene autotemcel (beti-cel, Zynteglo), its marketed gene therapy for transfusion dependent thalassemia (TDT). As such, bluebird bio has reported 23 total cell collections for SCD/TDT gene therapies lovo-cel and beti-cel. The company expects that patient uptake of the 3 aforementioned therapies will continue to increase, with 85 patient starts expected across the therapies by the end of the year.

“We are seeing clear evidence that our commercial launch is accelerating, with over 20 cell collections completed in SCD and TDT to date in 2024, and more than 40 additional patients already scheduled to initiate the treatment journey for a bluebird gene therapy by the end of this year,” Andrew Obenshain, MBA, the chief executive officer of bluebird bio, said in a statement.

 “We are further encouraged by the commitment to provide patient access across both commercial and government payers, most recently conveyed through multiple positive Medicaid decisions and the growing number of published coverage policies for Lyfgenia, and we expect approximately 85 patient starts across our portfolio this year.”

Notably, unlike lovo-cel, exa-cel is indicated for both SCD and TDT. Since Vertex has not clarified the breakdown of patients treated with exa-cel for each disease, direct comparison is difficult. The approval in TDT came slightly later, with 

“Vertex delivered another strong quarter of revenue growth coupled with outstanding execution across the business, and we are increasing our full year product revenue guidance,” Reshma Kewalramani, MD, the chief executive officer and president of Vertex, said in an August 1, 2024, statement.

 “Our focus for the second half of the year remains on commercial execution in cystic fibrosis and the global launch of Casgevy, readying for the upcoming potential launches of the vanzacaftor triple in cystic fibrosis and suzetrigine in acute pain, while rapidly advancing a robust pipeline that is poised to deliver value for patients and shareholders for the long term.”

Beyond gene therapy for SCD and TDT, uptake of 

hemophilia gene therapies has also been slow

. Although BioMarin’s valoctocogene roxaparvovec (val-rox, marketed as Roctavian) was approved in June 2023, the first patient outside of clinical trials 

 until December 2023, at the Center for Inherited Bleeding Disorders (CIBD) in California.

 Just this month, BioMarin announced that 

 with regard to val-rox, with the company now mainly focusing on distributing the gene therapy in the United States, Germany, and Italy, the 3 countries in which it has been approved for use by relevant regulatory authorities and is reimbursed.

 UniQure and CSL Behring’s hemophilia B gene therapy, etranacogene dezaparvovec (marketed as Hemgenix), which was 

, has also been slow to be embraced by patients.

“We haven't seen a lot of patients dosed yet,” Steven W. Pipe, MD, a professor of pediatric hematology/oncology at CS Mott Children’s Hospital, told 

 regarding Hemegenix earlier in 2024. “And I don't think that’s related to either the enthusiasm of the clinicians or the patients, but really just the mechanics of how to deliver this in the clinical space, as opposed to the research trials... We've seen that a lot of the hemophilia treatment center sites have got their components together, their infrastructure and personnel so that they can actually start delivering this in the commercial setting. And so, I'm really looking forward to seeing this making a difference in patients' lives in a real world setting.”

REFERENCES
1. bluebird bio reports second quarter 2024 results and highlights operational progress and 2024 guidance. News release. bluebird bio, Inc. August 14, 2024. Accessed August 15, 2024. https://investor.bluebirdbio.com/news-releases/news-release-details/bluebird-bio-reports-second-quarter-2024-results-and-highlights
2. Stock dive for bluebird as sickle cell gene therapy lags behind Vertex rival. News article. Anna Bratulic. FirstWord Pharma. August 14, 2024. Accessed August 15, 2024. https://firstwordpharma.com/story/5885598
3. Vertex announces US FDA approval of CASGEVY™ (exagamglogene autotemcel) for the Treatment of Transfusion-Dependent Beta Thalassemia. News release. Vertex Pharmaceuticals Incorporated. January 16, 2024. Accessed August 15, 2024. https://news.vrtx.com/news-releases/news-release-details/vertex-announces-us-fda-approval-casgevytm-exagamglogene
4. Vertex reports second quarter 2024 financial results. News release. Vertex Pharmaceuticals Incorporated. August 1, 2024. Accessed August 15, 2024. https://investors.vrtx.com/news-releases/news-release-details/vertex-reports-second-quarter-2024-financial-results
5. Center for Inherited Blood Disorders Administers Country's First Gene Therapy Infusion to Treat Hemophilia A. News release. Center for Inherited Blood Disorders. January 11, 2024. Accessed August 15, 2024. https://firstwordpharma.com/story/5817834?from=article
6. BioMarin Announces Updated Strategy for ROCTAVIAN® to Focus on U.S., Germany and Ital. News release. BioMarin Pharmaceutical Inc. August 5, 2024. Accessed August 15, 2024. https://investors.biomarin.com/news/news-details/2024/BioMarin-Announces-Updated-Strategy-for-ROCTAVIAN-to-Focus-on-U.S.-Germany-and-Italy/default.aspx
7. FDA approves first gene therapy to treat adults with hemophilia B. News release. FDA. November 22, 2022. Accessed August 15, 2024. https://www.fda.gov/news-events/press-announcements/fda-approves-first-gene-therapy-treat-adults-hemophilia-b

bluebird bio has reported 23 total cell collections for SCD and TDT gene therapies lovo-cel and beti-cel and Vertex Pharmaceuticals has reported approximately 20 cell collections for SCD/TDT gene therapy exa-cel.

Topic

Uptake of Nononcology Gene Therapy Remains Slow in Hematology

(arsa-cel, OTL-200; Orchard Therapeutics) is a gene-edited cell therapy designed to restore arylsulfatase A (ARSA) enzyme activity in children with presymptomatic (PS) late infantile (LI), PS early juvenile (EJ), or early symptomatic (ES) early juvenile (EJ) metachromatic leukodystrophy (MLD).

 arsa-cel under the name Lenmeldy to become the first gene therapy for children with MLD to be approved in the United States, following its approval in the European Union, UK, Iceland, Switzerland, Liechtenstein and Norway under the name Libmeldy.1 Orchard Therapeutics previously announced that the FDA had accepted the biologics license application with 

The FDA’s decision was based on data from patients treated with arsa-cel across 2 clinical trials (NCT01560182; NCT03392987) and additional patients treated in expanded access frameworks. These patients had follow-up times ranging from 0.64 years to 12.19 years (median, 6.76).

“Metachromatic leukodystrophy, is a really important unmet need in the pediatric community. So, this is a disease that's rare, it affects about one in 40,000 children. And up until recently, we have had no curative treatment option for this,” Madeleine Powys, MBBS, Staff Specialist, Blood Transplant and Cell Therapies, The Children's Hospital at Westmead, told 

. "Autologous hematopoietic stem cell gene therapy has offered really promising new hope for these patients.”

Madeleine Powys, MBBS, on Lessons Learned With Libmeldy

Arsa-cel is currently being evaluated in 6 participants enrolled in a phase 3 clinical trial (NCT04283227). The trial enrolled participants with documented biochemical and molecular diagnosis of MLD, including low ARSA activity and identification of 2 disease-causing ARSA alleles, with novel mutations analyzed and excluded as common polymorphisms, alongside specific genotype criteria. Symptomatic individuals must have onset between 7 and 17 years of age, or pre-symptomatic participants must be less than 17 years at treatment initiation and have a sibling with late-juvenile MLD variant, along with normal cognitive and motor function, with seizures or disease signs revealed by instrumental evaluations not being exclusionary if present alone, and compliance with contraceptive use requirements if applicable, with signed informed consent or assent provided by the participant or guardian.

The exclusion criteria for the study include documented HIV infection, malignant neoplasia except localized skin cancer or hereditary cancer syndrome unless successfully treated with no recurrence, myelodysplasia, acute myeloid leukemia, or serious hematological disorders, current enrollment in other interventional trials, prior allogeneic HSPC gene therapy or gene therapy, symptomatic herpes zoster unresponsive to treatment, active tuberculosis unless on antibiotic prophylaxis, acute or chronic stable Hepatitis B or positive Hepatitis C RNA test result unless specific conditions are met, end-organ dysfunction, severe infection not responsive to treatment, or other severe diseases deemed inappropriate for the study by the investigator. Additionally, testing for other transmissible infectious agents may be considered, and participants with elevated liver enzymes or bilirubin may be included after discussion and agreement with the medical monitor.

The study’s primary measures involve assessing the OTpbmsL-200 Arylsulfatase A (ARSA) activity levels in cerebrospinal fluid (CSF) and the neuronal metabolite ratio of N-acetyl-aspartate (NAA) to creatine (Cr) in white matter brain regions, both evaluated at 24 months post-treatment, with changes from baseline being monitored.

Secondary measures involve evaluating changes in ARSA activity levels in CSF and neuronal metabolite ratio in white matter brain regions, assessing ARSA levels in peripheral blood mononuclear cells (PBMCs) and specific subtypes, comparing neuronal metabolite ratios to baseline, siblings, or untreated controls, determining engraftment through lentiviral positivity in bone marrow progenitors and vector copy number in BM cells and PBMCs, assessing severity scale for brain MRI, neurocognitive function, full neurological clinical examination, gross motor function classification, nerve conduction velocity, Vineland Adaptive Behavior Scale, and monitoring conditioning regimen and non-conditioning-related adverse events up to 8 years post gene therapy, along with hematological reconstitution, infusion-related reactions, immune response, abnormal clonal proliferation, replication-competent lentivirus, and integration site analysis findings over time.

, held February 4-9, in San Diego, California, by Vera Gallo, MD, staff pediatrician, San Raffaele Telethon Institute for Gene Therapy. The data were from 5 patients with LJ MLD that had follow-up ranging from 3.2 to 21.3 months (median, 17.3). At the time of treatment, 3 patients had PS MLD and 2 had ES MLD. The group included a 2.7-year-old girl (PS), a 9.9-year-old boy (ES), a 15.2-year-old boy (PS), a 6.6-year-old girl (PS), and 10.9-year-old boy (ES) as of the December 2023 cutoff date.

"This represents of course, the proof of principle that gene therapy with ex- vivo lentiviral gene therapy into stem cells can correct a lysosomal storage disorder (LSD)... and could be applicable to other LSDS. So we're working on new diseases to bring this approach of enzyme correction also to other LSDs," investigator Alessandro Aiuti, MD, PhD, deputy director, clinical research, and head, Clinical Research Unit, San Raffaele Telethon Institute for gene therapy, and Group leader, Pathogenesis and therapy, primary immunodeficiencies unit, and full professor, Università Vita Salute San Raffaele, and chief of clinic, Pediatric Immunohematology Unit, San Raffaele, told 

Data from these participants showed that they all had normal hematological reconstitution and engraftment that was consistent with arsa-cel outcomes seen in patients with early-onset MLD who have been treated in other settings. Time to neutrophil engraftment ranged from 26 to 42 days (median, 33) posttreatment and time to platelet engraftment ranged from 25 to 46 days (median, 26) posttreatment. ARSA activity reached supranormal levels in the PBMCs and in CD15+ cells and increased to normal levels in the CSF in 3 patients for whom central nervous system pharmacodynamic efficacy measures were available.At 90 days after administration of arsa-cel transduced bone marrow progenitors made up between 23.81% to 81.25% of bone marrow progenitors. At this time point, the PBMCs showed a median vector copy number (VCN) of 0.49 copies/cell and the CD15+ cells showed a median VCN of 0.82 copies/cell.

In terms of safety, there were no serious adverse events (SAEs) deemed potentially related to arsa-cel. One nonserious AE deemed potentially related to the therapy, a case of erythematous rash, occurred in 1 patient. No SAEs deemed potentially related to the Busulfan conditioning regimen occurred; although cases of febrile neutropenia, cytopenia, and stomatitis were deemed to have potential relation to the regimen. An SAE of upper respiratory tract infection occurred in 1 patient. One patient with prolonged thrombocytopenia who had previously experienced treatment-failure with allogeneic transplant in the form of autologous reconstitution was administered thrombopoietin receptor agonist therapy for 5 months. No multilineage engraftment of transduced cells or malignancy occurred and there was no indication of clonal expansion or replication competent lentivirus.

1. FDA Approves First Gene Therapy for Children with Metachromatic Leukodystrophy. News release. Orchard Therapeutics. March 18, 2024. Accessed March 18, 2024. https://www.fda.gov/news-events/press-announcements/fda-approves-first-gene-therapy-children-metachromatic-leukodystroph
2. Orchard Therapeutics announces acceptance of biologics license application for OTL-200 in MLD and receives priority review. News release. Orchard Therapeutics. September 18, 2023. Accessed September 18, 2023. https://ir.orchard-tx.com/news-releases/news-release-details/orchard-therapeutics-announces-acceptance-biologics-license
3. Fumagalli F, Calbi V, De Mattia F, et al. Long-term clinical outcomes of atidarsageneautotemcel (autologous hematopoietic stem cell gene therapy) preserves cognitive and motor development in early-onset metachromatic leukodystrophy with up to 12 years follow-up. Presented at: WORLDSymposium, held February 4-9, in San Diego, California. Poster #92
4. Gallo V, Calbi V, De Mattia F, et al. Lentiviral hematopoietic stem cell gene therapy (atidarsageneautotemcel) for late juvenile metachromatic leukodystrophy (MLD). Presented at: WORLDSymposium, held February 4-9, in San Diego, California. Poster #96

The gene-edited cell therapy has been approved as Lenmeldy by the FDA. 

Phase 3 Trial Seeks to Continue Supporting Arsa-Cel Gene Therapy for MLD 

A few years ago, Mass General Brigham established its Gene and Cell Therapy Institute (GCTI) with the goal of helping innovative preclinical research in the field make its way into first-in-human clinical trials. At 

the American Society of Gene & Cell Therapy (ASGCT) 28th Annual Meeting

, held May 13 to 17, 2024, in New Orleans, the GCTI gave several presentations related to its mission.

spoke with Roger Hajjar, MD, the director of the GCTI, to learn more about the Institute and its activities. Hajjar described what makes the GCTI unique in the field and discussed some highlights from the Institute's presentations at ASGCT this year.

: Could you give some background info about the GCTI? What makes it unique?

The GCTI at Mass General Brigham was initiated around 2 and a half to 3 years ago with the specific mission of bringing together over 500 investigators who focus on gene and cell therapies across Mass General and Brigham. These laboratories are focused very much on early stage and preclinical work, and our goal as an institute is to bring these projects that are early stage into first-in-human trials. To do that, we've taken the approach of creating a platform for these investigators to help with manufacturing, with regulatory interactions, with trial design, and also focusing on funding and different sources of funding to bring these projects into first-in-human trials. That's really been the focus of the Institute since its start. 

We've also been able to create specific type of "cores" that help with these types of investigations. These include AAV cores, RNA therapeutics cores... other cores, such as cell therapy cores, for specific types of induced pluripotent stem cell-derived neuronal cells, for example—and to have a good manufacturing practice (GMP) facility within Mass General Brigham, to have more point-of-care type of treatments—that's really been the mission and the differentiator for the Institute: to really bring together a set of platforms to help our investigators get to first-in-human [trials] because overall, the mission of the academic medical center that we're in is to help patients and to bring novel therapies to them.

Is there anything GCTI is presenting at the conference this year that you would like to highlight?

Our investigators across MGB have different areas [of interest such as] in pediatric neurology, cardiovascular disease, etc.—the Institute has a focus on how to translate early stage investigators to clinical trials. We have a poster depicting that. This transition from early-stage to clinical trials in the gene and cell therapy space is quite unique because of all the different areas that need to be addressed for gene and cell therapies. How do you manufacture, since our investigators use different modalities and different delivery systems? How do you engage with the regulatory entities? How do you design a trial that's going to be able to effectively show biological effects for the treatment? That's what we've been focusing on and that's what's being presented here at the ASGCT meeting this year.

This transcript has been edited for clarity.

Click here to view more coverage of the 2025 ASGCT Annual Meeting.

Roger Hajjar, MD, the director of the Mass General Brigham Gene and Cell Therapy Institute, also discussed the Institute’s presentations at ASGCT’s 2025 conference.

Helping to Bring Preclinical Gene Therapy Research to First-in-Human Trials

A patient has passed away after treatment with Rocket Pharmaceuticals’ RP-A501, an investigational adeno-associated virus serotype 9 (AAV9) vector-based gene therapy intended to treat Danon disease, in the context of a pivotal phase 2 clinical trial (NCT06092034).

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. A comprehensive root cause analysis is currently being carried out by the company, which is in active communication with the FDA and other important stakeholders. A current focus of this analysis is a novel immune suppression agent specific to the AAV9-Danon program that was recently added to the gene therapy’s pretreatment regimen with the intention of reducing complement activation, a phenomena that had been seen in some participants.

Rocket stated that dosing in the trial was paused when it became aware of the SAE and that the FDA put a clinical hold on the trial on May 23, 2025, to enable continued evaluation of the event. The company noted that it is currently working with the FDA, the study’s independent data safety monitoring committee, clinical investigators, and scientific experts with regard to the SAE, and that it intends to continue the trial as soon as it can safely do so. Although, an estimated completion date for the study can not be provided until the clinical hold is resolved.

“We are heartbroken by this loss and are fully committed to our mission to develop gene therapies that address the underlying cause of devastating diseases like Danon,” Gaurav Shah, MD, the chief executive officer of Rocket Pharmaceuticals, said in a statement.

 “We are immensely grateful for the patients and families who participate in this important research.”

Rocket originally announced that the phase 2 trial 

 in September of last year, with 12 male patients having been enrolled across sites in the United States and Europe.

 GC/kg of the gene therapy and 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. RP-A501 was previously evaluated in a phase 1 clinical trial (NCT03882437) for patients with Danon disease.

 were presented at the American Heart Association (AHA) Scientific Sessions 2024 by Joseph Rossano, MD, MS, FAAP, FACC, the Jennifer Terker Endowed Chair in Pediatric Cardiology, codirector of the Cardiac Center, and chief of the Division of Cardiology at the Children's Hospital of Philadelphia, and published in the 

 Treatment with the gene therapy product showed evidence of LAMP2 expression in 6 patients’ immunohistochemical analysis, and in 5 of 6 evaluable patients in the 24- to 36-month window. A reduction of left ventricular mass index by at least 10% after 12 months, sustained up to 54 months post infusion, was also reported. The therapy was deemed generally well-tolerated, with all patients alive and in stable condition after more than 4 years of follow-up.

“In our phase 1, open-label study, we observed improvements in New York Heart Association class and KCCQ-12 [Kansas City Cardiomyopathy Questionnaire] scores (ranging from 0 to 100, with higher scores indicating better health status) of at least 5 points in all 6 evaluable patients,” Rossano et al wrote.

 “Improvements in KCCQ-12 of 5 points or more are considered to be clinically meaningful in adults. Most of the patients—many of whom in the absence of this therapy would have probably had end-stage heart failure or died—reported full participation in school, work, and leisure-related activities after RP-A501 treatment.”

REFERENCES
1. Rocket Pharmaceuticals provides update on phase 2 clinical trial of RP-A501 for Danon disease. News release. Rocket Pharmaceuticals, Inc. May 27, 2025. Accessed May 27, 2025. https://ir.rocketpharma.com/news-releases/news-release-details/rocket-pharmaceuticals-provides-update-phase-2-clinical-trial-rp
2. Rocket Pharmaceuticals announces completion of enrollment in phase 2 pivotal trial of RP-A501 for the treatment of Danon disease. News release. September 17, 2024. Accessed September 19, 2024. https://ir.rocketpharma.com/news-releases/news-release-details/rocket-pharmaceuticals-announces-completion-enrollment-phase-2
3. Greenberg B, Taylor M, Adler E, et al. Phase 1 Study of AAV9.LAMP2B Gene Therapy in Danon Disease. N Engl J Med. Published online November 18, 2024.doi:10.1056/NEJMoa2412392
4. Rossano J. Danon Disease Phase 1 RP-A501 Results: The First Single-Dose Intravenous Gene Therapy with Recombinant Adeno-Associated Virus (AAV9:LAMP2B) for a Monogenic Cardiomyopathy. Presented at: AHA Scientific Sessions November 16-18, 2024; Presentation 4168378


The patient’s death occurred after an acute systemic infection and was associated with an unexpected SAE of clinical complications related to capillary leak syndrome.

Patient Dies After Treatment With Rocket Pharmaceuticals’ Danon Disease Gene Therapy RP-A501 in Phase 2 Trial

The CEO of Mission Bio discussed the company’s single cell assay platform in the context of the broader developing field cell and gene therapy field. 

Brian Kim, MBA, on Multiomic Single Cell Sequencing and the Ebbs and Flows of the Gene Therapy Field

“I think this is an interesting time we're living in right now and cell and gene therapy is going through a transition period right now, but I think it's really important to note that it's a transition period. I don't think people should really lose too much sleep that this is going to go away. A lot of drug modalities and technologies have these ebbs and flows, but we just saw this morning there was an announcement by the New York Times that a little baby was saved with a CRISPR-based therapeutic for a very rare genetic disorder that this child had. When you see things like that happening with patients with the therapies that we have right now, you know that it's going to go someplace in the future.”

Mission Bio is seeking to overcome limitations of bulk sequencing and standard single cell sequencing methods through the use of its Tapestri platform for single cell sequencing. At 

, held May 13 to 17, 2024, in New Orleans, LA, the company gave several presentations related to its platform and the ways in which it is contributing to the development of the field of cell and gene therapy.

 spoke with Brian Kim, MBA, the chief executive officer of Mission Bio, to learn more. Kim explained that the company offers a single-cell multiomic platform focused on validation for therapeutic and diagnostic purposes and highlighted the presentations the company gave at ASGCT this year. Kim also took a broader view and emphasized that despite current challenges in cell and gene therapy, the field is progressing, with recent news of patient successes reinforcing its potential. He pointed out that Mission Bio remains committed for the long haul, having supported over 17 clinical trials and working to expand adoption of its assays. Future plans for the company include adding targeted gene expression to their platform and seeking to foster more collaborations.

The CEO of Mission Bio discussed the company’s single cell assay platform in the context of the broader developing field cell and gene therapy field.

Videos

Brian Kim, MBA, on Multiomic Single-Cell Sequencing and the Ebbs and Flows of the Gene Therapy Field

, held February 3 to 7, 2025, in San Diego, California, data from clinical trials evaluating gene therapy products for the treatment of Fabry disease were among those presented. This included data from the ongoing phase 1/2 STAAR clinical trial (NCT04046224) evaluating isaralgagene civaparvove (ST-920), Sangamo Therapeutics’ investigational adeno-associated virus (AAV) vector-based gene therapy for Fabry disease, and data from a completed phase 1 clinical trials referred to as FACTS (NCT02800070). 

Following up on Fabry Disease Awareness Month, observed annually in the month of April, 

 got in touch with Aneal Khan MD, MSc, FCCMG, FRCPC, the president of MAGIC Clinic and CEO of Discovery DNA, to discuss gene therapy research in Fabry disease. Khan spoke about the data presented at WORLD

and about innovation in the field more generally. 

Can you give some background context about Fabry disease?

 Fabry disease is an X-linked genetic disease that affects both males and females. The main features include heart and kidney disease, stroke, and pain. These features can start in childhood, especially in males who can have early onset severe pain episodes, with silent progression of the organ disease and reduced life expectancy if untreated. There is no cure for Fabry disease. Current standard treatments include enzyme replacement therapy or oral chaperone therapy which needs to be taken at regular intervals for life.

Can you discuss the Fabry disease data presented at World

Data on gene therapies were presented. This includes outcomes of the Sangamo gene therapy trial and the FACTS gene therapy trial. These therapies are quite different in the sense that Sangamo is a trial using an AAV-like vector directly injected into the body (in vivo gene therapy). The FACTS trial takes stem cells from the body and administers a lentiviral vector outside the body into the stem cells and then injects the stem cells back into the patient (ex vivo gene therapy). Both types of gene therapy are in clinical trials.

How would you summarize the big-picture implications that doctors and the broader healthcare community should take away from this data?

The gene therapies offer the possibility of a once-in-life treatment by inserting a working copy of the 

 gene into the patient. These patients have been shown to make enough enzyme from the gene therapy to not be classified as enzyme-deficient. Studies are ongoing to see how well these therapies reduce the disease symptoms and organ involvement in patients with Fabry disease.

Have there been any challenges so far and/or have there been any areas of interest identified for further study?

Some patients have had mild inflammatory changes, such as liver inflammation, which has been temporary and [to my knowledge] no serious adverse events have been reported.

Do you have a main message you would like to share with the healthcare community for Fabry Disease Awareness Month in 2025?

When I started my career, there was no treatment for Fabry disease. Enzyme replacement therapy, which has been in place now for about 20 years, has really improved the outcomes for patients with Fabry disease. Oral therapies have made it easier to take the treatment rather than having an enzyme infusion. So, there is hope that one day a “one and done” therapy, like gene therapy, may offer patients with Fabry disease and easier way to live with Fabry disease and improve outcomes.

Is there anything not covered by the previous questions that you want to share?

Collecting data from studies takes time and a lot of dedication from the patients. The patients are essential in driving the technology forward and all of the patients I have had in clinical trials are involved to really help develop newer treatments that could be used in patients with those diseases in the future. While much has been reported about some gene therapy trials where there were negative outcomes, thousands of people with different diseases have now been treated in gene therapy trials safely and patients in this trial from Sangamo generally are healthy and continuing to do well.

The president of MAGIC Clinic and CEO of Discovery DNA discussed the implications of gene therapy data presented at the 2025 WORLDSymposium.

David L. Porter, MD, University of Pennsylvania

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