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The former FDA commissioner discussed the necessity of policy and funding efforts for neuromuscular disorders, the stress on the clinical care system, and the need to acknowledge healthcare inequities.

Robert M Califf, MD, MACC, on Urgency of Funding and Equity in Neuromuscular Research and Care

The commissioner of food and drugs at the FDA discussed the year's approvals and what may be coming on the horizon in the realm of advanced therapeutics.

Robert M Califf, MD, MACC, on 2023’s Landmark FDA Approvals of Cell and Gene Therapies

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 

This article originally appeared on our sister site,

On the last day of February each year, Rare Disease Day is held. An international awareness campaign, Rare Disease Day is intended to to shine light on the challenges faced by people living with rare diseases and to facilitate advocacy for equitable access to diagnosis, research, and treatment. Originally launched in 2008 by the European Organization for Rare Diseases (EURORDIS), Rare Disease Day has garnered global participation in the years since. It involves patient advocacy groups, healthcare professionals, those involved in scientific research, policymakers, and the general public.

Rare diseases are defined as those affecting fewer than 1 in 2000 people. More than 7000 rare diseases have been identified to date, and together these disease affect more than 300 million people across the globe.

One such rare disease is SLC6A1-related neurodevelopmental disorder, also known as SLC6A1 Deficiency Disorder, a rare genetic condition characterized by mild-to-moderate developmental delay and/or intellectual disability, hypotonia, epilepsy, movement disorders, and neurobehavioral and/or psychiatric manifestations. Fewer than 500 people in the world have reported cases of SLC6A1 as of 2020, indicating an estimated incidence of 2.65 in 100,000 births for the disease.

In 2018, Amber Freed founded SLC6A1 Connect, an advocacy organization dedicated to raising awareness, advancing research, and supporting families affected by SLC6A1-related disorders. Freed, whose son was diagnosed with the condition, sat down with

®, to shed light on the daily struggles faced by families, from disrupted routines to the challenges of caregiving and finding informed clinicians. Highlighting the importance of Rare Disease Day, she emphasized the urgent need for funding and awareness to advance gene therapy research, particularly her collaboration with the Steve Gray Lab to develop a potential cure. Overall, she advocates for precision medicine as the future of treatment for rare diseases and called for greater activism within the community to accelerate progress.

 What are some of the lesser-known aspects of SLC6A1 disease?

 I founded SLC6A1 Connect when my son Maxwell was diagnosed with the genetic variant SLC6A1. It’s a rare genetic epilepsy, and along with seizures come a lot of behavioral deficits, a movement disorder, speech apraxia, and intellectual disability. He just struggles. I think one thing people don’t really understand about the disorder is that there’s so much more than just epilepsy. It’s everyday tasks. It’s trying to teach someone whose brain is “on fire” and having an incredibly hard time trying to learn.

 is a gene that codes for GAT1, which controls the body’s most important neuroinhibitory transmitter. If your brain is not inhibited, that’s bad—you can just imagine trying to get through your day like that. Rare Disease Day helps bring awareness to just how important these conditions are and what the daily struggles look like. Our community has a huge unmet need. The term autism is very broadly used, but when you narrow it down to the symptoms, it highlights what a typical day is like. Our poor kids have a really hard time sleeping—they don’t understand the difference between day and night. It’s really hard for them to be awake during the day, and meal times are all messed up. That’s not going to change because of this genetic abnormality. As you can imagine, that leads to a very tough family life. Siblings want to have sports and school activities, but it’s hard when it typically takes the full-time attention of two parents to care for just one child.

Are there any SLC6A1-related research or initiatives that need greater attention or focus?

When Maxwell was diagnosed, we figured out he’s missing half of a pretty important gene. The most eloquent solution is to just replace what’s missing, and the technology exists today to do that. The only thing holding us back is money. Since his diagnosis in 2018, we’ve had a laser focus on achieving that. We’re working with the Steve Gray lab at UT Southwestern, and we’ve raised $6 million philanthropically to get to that goal. Now, this Rare Disease Day, we’re announcing the next step: toxicology. Our next fundraising goal is $750,000 to get through the final toxicology studies and then actually start treating humans. That will be the closest thing to a cure our kids will see in our lifetime.

It’s super expensive for us, but like with any technology, it starts big and costly, like old cell phones, and eventually becomes smaller, more accessible, and affordable. The work we’re doing today is going to help so many people in the future.

Are there ways we can help patients with their intellectual disabilities?

Intellectual disability and behavior are really tough. For kids with rare genetic epilepsies, it’s hard to know what their intellect truly is because they’re trapped in their bodies. We all know there’s so much more going on inside than what we see on the outside. But a lot of times, they’re nonverbal or can’t express themselves. I believe the future for epilepsy and rare diseases lies in personalized, precision medicine, just like how cancer treatment has evolved.

You’re no longer diagnosed with just “breast cancer.” It’s a specific variant, and your doctor designs a treatment just for you. There’s no reason we can’t do the same for epilepsy and neurological conditions. The earlier we treat people with a precision approach, the better. It keeps them from carrying these challenges into adulthood. Parents live with this dark fear—what happens to my child when I die? Who will take care of them? There’s no place for them in society, and they need full-time caretakers. That’s such a sad life for them. Let’s fix it from the beginning. Let’s replace what’s missing so they can go on to be the best versions of themselves.

How difficult is it to find a clinician who’s versed in SLC6A1 disease?

It’s very difficult to find a doctor who fully understands SLC6A1. It’s taken a lot of, for lack of a better term, “dating” to find doctors who are passionate about research, inspired by the rare disease community, and who truly understand the unmet need. I coach patients to feel empowered to educate their doctors about the disease. Take in a one-pager that explains what it’s like. Don’t hold back. Don’t sugarcoat things—you’ve got 15 to 30 minutes of their time, so make it count.

This Rare Disease Day, I want to encourage patients, doctors, and scientists to be activists. Think about where we were in the ‘80s and ‘90s with HIV/AIDS or with cancers in the early 2000s—that’s where we are with rare diseases now. For the first time, we’re able to identify not just a gene diagnosis but a potential cure. It’s going to take more awareness, more action, more walks, and more outreach to our senators and congresspeople. We need to educate them on why this matters. We have a chance to change the future of medicine today, so let’s take it. We’re never going to solve complex diseases like Alzheimer disease if we can’t knock out these simpler diseases first.

This transcript has been edited for clarity.

In honor of Rare Disease Day, observed this year on February 28, Amber Freed, the founder of SLC6A1 Connect, shared thoughts on advocacy and efforts to raise awareness for rare genetic disease SLC6A1.

Canonical

Transforming Challenges Into Action for SLC6A1

This video originally appeared on our sister site,

The director of the Autologous Hematopoietic Cell Transplantation, Cell Therapy and Transplant Program at the Hospital of the University of Pennsylvania discussed data from the phase 2 BMT CTN 1902 trial.

Bhagirathbhai R. Dholaria, MD, on Evaluating P-BCMA-ALLO1 in R/R Myeloma

“We set a bar for ourselves to see if we could increase [the proportion of patients who converted to a complete response (CR)] to at least 30%, and what we found actually was that we did even better than that by a good amount. Sixty-three percent of patients converted to CR, and another 24% upgraded their response in some other way. A total of 87% of patients improved their response to some extent.”

Bristol Myers Squibb and 2seventy bio's idecabtagene vicleucel (ide-cel, marketed as Abecma), an FDA-approved chimeric antigen receptor T-cell (CAR-T) therapy, is currently being evaluated in conjunction with subsequent lenalidomide (Revlimid) maintenance in the phase 2 BMT CTN 1902 clinical trial (NCT05032820) for the treatment of patients with multiple myeloma (MM) who had a suboptimal response following upfront autologous stem cell transplant (ASCT) and maintenance lenalidomide. Data from this study were recently presented at 

the 2025 Tandem Meetings |Transplantation & Cellular Therapy Meetings of ASTCT and CIBMTR

, held in Honolulu, Hawaii, February 12 to 15, 2025, by Alfred L. Garfall, MD, MS, the associate professor of medicine (hematology-oncology) and director of the Autologous Hematopoietic Cell Transplantation, Cell Therapy and Transplant Program at the Hospital of the University of Pennsylvania.

, spoke with Garfall to learn more. In an interview with 

, Garfall explained that, historically, patients who do not achieve a complete response (CR) following ASCT and lenalidomide maintenance do not typically convert to a CR down the line, and noted that for BMT CTN 1902, the investigators projected that this happens in approximately 10% of patients. As such, the primary end point for the study was set as the CR rate at 6 months following ide-cel infusion, with the goal of increasing that rate to at least 30%.

 that 63% of patients (n =38) achieved a CR, and an additional 24% of patients experienced an upgraded response without reaching a CR, leading to an overall response improvement rate of 87%.

With regard to safety, cytokine release syndrome (CRS) was observed in 81.6% of patients, with all cases limited to grade 1 (68.4%) or grade 2 (13.2%). The median time to CRS onset was 1 day (range, 0-4), with resolution occurring at a median of 2.5 days (range, 0-6). Tocilizumab was administered in 77% of cases, and corticosteroids were used in 23% of patients with CRS. Notably, there were no cases of immune effector cell–associated neurotoxicity syndrome observed.

Click here for more coverage of Tandem 2025.

Videos

Alfred L. Garfall, MD, MS, on Ide-Cel and Lenalidomide Maintenance in MM Following Suboptimal ASCT Response

The cell and gene therapy sectors are growing exponentially, with new players emerging daily and much progress being made both in and out of the lab. 

®’s Around the Helix is your chance to catch up with the latest news in cell and gene therapies, including partnerships, pipeline updates, and more.

Have a cell and gene therapy news update you’d like to share with our editorial team? Tag us on social (

1. Phase 2 Trial for BMS's Liso-Cel Meets Primary End Point in R/R Marginal Zone Lymphoma Cohort

Bristol Myers Squibb (BMS)’s phase 2 TRANSCEND FL clinical trial (NCT04245839) evaluating lisocabtagene maraleucel (liso-cel, marketed as Breyanzi), an autologous CD19-directed chimeric antigen receptor T-cell (CAR-T) therapy, has met its primary end point in its cohort for adult patients with relapsed/refractory (r/r) marginal zone lymphoma (MZL).

2. CareDx’s AlloHeme Shows Accuracy in Detecting Relapse Following AlloHSCT in AML and MDS

CareDx’s AlloHeme, a next-generation sequencing (NGS)-based assay, has demonstrated the ability to detect early relapse following allogeneic hematopoietic stem cell transplantation (alloHSCT) in patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), according to interim data from the prospective ACROBAT study (NCT04635384).

3. Keys to a Successful Cell and Gene Therapy Launch

The obstacles to affordability and accessibility are complex and multifactorial; they include the complex, high-cost manufacturing processes for personalized living therapies, long vein-to-vein times, complicated logistics, their often-curative nature, and high prices. Addressing these challenges effectively requires therapy developers to consider affordability and accessibility from early development alongside the traditional focus on safety and efficacy, which drive approvability.

4. Solid Biosciences’ Gene Therapy SGT-003 Produces Microdystrophin Expression in Patients With DMD

Solid Biosciences SGT-003, an investigational next-generation adeno-associated virus (AAV) vector-based gene therapy, has produced expression of microdystrophin in patients being treated for Duchenne muscular dystrophy (DMD) in the phase 1/2 

INSPIRE DUCHENNE clinical trial (NCT06138639)

5. Biogen Purchases Certain International Commercial Rights for Stoke Therapeutics' Dravet Syndrome Gene Therapy

Biogen has purchased the rights to develop and commercialize Stoke Therapeutics' zorevunersen (also known as STK-001), an investigational antisense oligonucleotide (ASO) intended to treat Dravet syndrome, in all territories outside the United States, Canada, and Mexico. Notably, Stoke expects to initiate EMPEROR, a planned global phase 3 registrational clinical trial for zorevunersen, in the second quarter of this year. 

6. AskBio Snags RMAT Designation for Parkinson Disease Gene Therapy AB-1005 

Asklepios BioPharmaceutical (AskBio)'s AB-1005 (AAV2-GDNF), an investigational AAV vector serotype 2 (AAV2)-based gene therapy intended to treat Parkinson disease (PD), has received regenerative medicine advanced therapy (RMAT) designation from the FDA. Notably, a sham-controlled phase 2 clinical trial (REGENERATE-PD; NCT06285643) evaluating AB-1005, recently began the process of randomly assigning enrolled participants in January 2025.

7. FDA Accepts BLA for Ultragenyx’s MPSIII Gene Therapy UX111 With Priority Review

The FDA has accepted the biologics license application (BLA) that Ultragenyx submitted for UX111 (ABO-102), an AAV vector-based gene therapy intended to treat mucopolysaccharidosis type IIIA (MPS IIIA, also known as Sanfilippo syndrome), with priority review. The Prescription Drug User Fee Act (PDUFA) action date for the BLA has been set at August 18, 2025, and the FDA is not planning to hold an advisory committee meeting regarding the application.

8. Patient Treated in Bahrain Becomes First to Receive Vertex and CRISPR's SCD Gene Therapy Outside the US

The patient received Vertex Pharmaceuticals' and CRISPR Therapeutics’ autologous gene-edited cell therapy exagamglogene autotemcel (exa-cel, marketed under the name Casgevy) for the treatment of sickle cell disease (SCD) at The Bahrain Oncology Centre. Bahrain originally approved exa-cel for the treatment of SCD and transfusion-dependent beta-thalassaemia on December 2, 2023, becoming the first country in the Middle East and the second in the world to do so. 

Catch up on the latest news, breakthroughs, and announcements from biotechnology companies making advancements in cell and gene therapies. 

Around the Helix: Cell and Gene Therapy Company Updates – February 19, 2025

Sarepta Therapeutics’ delandistrogene moxeparvovec-rokl (marketed as Elevidys), a marketed adeno-associated virus (AAV) vector-based gene therapy for patients with Duchenne muscular dystrophy (DMD), has shown sustained benefit in patients who are ambulatory who were treated in the phase 3 EMBARK clinical trial (NCT05096221; SRP-9001-301), according to new results from part 2 of the study.

Among 59 patients in part 2 who crossed over to receive treatment with Elevidys after having received the placebo in part 1 of the study, a least square means (LSM) improvement of +2.34 points from baseline on the North Star Ambulatory Assessment (NSAA) in comparison to a matched external controlgroup (EC) at 52 weeks posttreatment (

 < .0001). In addition, the patients treated with Elevidys in part 2 also showed an LSM –2.70 seconds improvement on Time to Rise (TTR) (

 < .0001) and an LSM –1.07 seconds improvement on 10-meter walk/run (10MWR) (

= .0001) in comparison to a prespecified, propensity-weighted EC. Sarepta noted that the study remained blinded during the 52 weeks posttreatment period in part 2 and that the cross-over treated patients had an average age of 7.11 years, whereas the patients treated in part 1 of the study had had an average age of 5.98 years.

Sarepta also reported updated 2 year results from the 63 patients who originally received Elevidys in part 1 of EMBARK. At 2 years posttreatment, the patients treated with the gene therapy in EMBARK showed an LSM improvement of +2.88 points on NSAA (

 = .0033), and –1.36 seconds on 10MWR (

 =.0028) in comparison to EC. The company pointed out that an increased difference from 1 year posttreatment to 2 years posttreatment on NSAA, TTR, and 10MWR was observed between patients treated with Elevidys in part 1 and the EC, suggesting a continued widening of the chasm in disease trajectory between patients who received the gene therapy and the natural history course of the disease.

Sarepta also noted that consistent and sustained expression of the microdystrophin encoded by Elevidys was observed in biopsies taken from patients treated in part 1 at 12 weeks posttreatment and 64 weeks posttreatment. With regard to safety, the company stated that no new safety signals have been reported.

“We’re very encouraged to see the results from part 2 of EMBARK as they further elucidate the impact Elevidys has on disease progression in a blinded, controlled study,” Louise Rodino-Klapac, PhD, the executive vice president, head of R&D, and chief scientific officer of Sarapeta, said in a statement.

 “Skeletal muscle MRI demonstrates the importance of preserving muscle, and the functional outcome results show disease stabilization sustained through 2 years after treatment. Over time, we continue to observe a statistically significant difference favoring Elevidys compared to a well-matched external control on NSAA and timed tests. The consistency and totality of evidence supporting a long-term and clinically meaningful treatment benefit with Elevidys continues to grow. We look forward to sharing more details with the clinical community in upcoming scientific forums.”

The FDA originally approved Elevidys in June 2023 for ambulatory patients aged 4 through 5 years with DMD and a confirmed mutation in the 

 gene, excluding patients with any deletion in exon 8 and/or exon 9.

 in June 2024 to include ambulatory patients (via traditional approval) and nonambulatory patients (via accelerated approval) with a confirmed mutation in the 

 gene who are 4 years of age or older and who do not have any deletion in exon 8 or exon 9 in the gene.

, a pediatric neurologist in the Division of Neurology at Children’s Hospital of Philadelphia, to get his view on the newly emerging landscape of care for DMD and experience that had been gained with Elevidys at the time. He emphasized the need for more long-term data, especially for older patients, as many patients treated thus far have been on the younger end of the spectrum.

“While the label is broad and is for everyone we don't necessarily have the data to back that up yet and that makes the conversation more nuanced,” Brandsema told 

. “We also aren't sure about the durability of transgene expression. Muscle is a high turnover tissue, and therefore whether this is going to be a lifelong effect is still up in the air; although it does seem, from the early boys treated that there is a measurable difference in their trajectory years after the dose, up to 5 or 6 years at this point now.”

REFERENCES
1. Sarepta Therapeutics Announces Results from Part 2 of the EMBARK Study Demonstrating Sustained Benefits and Disease Stabilization in Ambulatory Individuals with Duchenne Muscular Dystrophy Following Treatment with ELEVIDYS. News release. Sarepta Therapeutics, Inc. January 27, 2025. Accessed January 29, 2025. https://investorrelations.sarepta.com/news-releases/news-release-details/sarepta-therapeutics-announces-results-part-2-embark-study?_ga=2.44245095.2103940291.1738162169-1590731373.1738162169
2. Sarepta Therapeutics Announces FDA Approval of ELEVIDYS, the First Gene Therapy to Treat Duchenne Muscular Dystrophy. News release. Sarepta Therapeutics. June 22, 2023. Accessed January 29, 2025. https://investorrelations.sarepta.com/news-releases/news-release-details/sarepta-therapeutics-announces-fda-approval-elevidys-first-gene
3. Sarepta Therapeutics Announces Expanded US FDA Approval of ELEVIDYS to Duchenne Muscular Dystrophy Patients Ages 4 and Above. News release. Sarepta Therapeutics, Inc. June 20, 2024. Accessed January 29, 2025. https://investorrelations.sarepta.com/news-releases/news-release-details/sarepta-therapeutics-announces-us-fda-acceptance-efficacy?_ga=2.242068545.254033713.1708093077-1826905377.1708093076


With regard to safety, the company stated that no new safety signals have been reported.

Robert M Califf, MD, MACC

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