CGTLive's 2024 Pillars of Progress: Most-Read Features

For all of 2024, our team was following the clinical development of targeted and novel engineered approaches to the treatment of patients with various medical disorders. These efforts included holding in-depth conversations with experts in the clinical care of these individuals, as well as in cell and gene therapy development, culminating in our coverage of each step of progress that the most exciting cellular and genetic treatments have made along the pipeline.

Part of those conversations resulted in our long-form approaches to reporting on the latest cell and gene news in the form of feature stories. When you spend all year bringing the latest information to the website's front page, sometimes there's a longer story to tell.

Here, we'll offer previews of some of the most-read features and long-form content from CGTLive'scoverage this year. Click the buttons to read further into these stories.

Real-World Experience With Duchenne Muscular Dystrophy Gene Therapy

Featuring commentary from:

• John Brandsema, MD
• Barry J. Byrne, MD, PhD
• Emma Ciafaloni, MD
• Michael Kelly, PhD
• Deborah Miller

Sarepta Therapeutics’ delandistrogene moxeparvovec-rokl (marketed as Elevidys), an adeno-associated virus (AAV) vector-based gene therapy for patients with Duchenne muscular dystrophy (DMD), was originally granted FDA approval under an accelerated approval pathway for a limited indication on June 22, 2023: ambulatory patients aged 4 to 5 years with DMD and a confirmed mutation in the DMD gene, excluding patients with any deletion in exon 8 and/or exon 9. Later, on June 20, 2024, the FDA approved the gene therapy for use in a broader indication: ambulatory patients (via traditional approval) and nonambulatory patients (via accelerated approval) with a confirmed mutation in the DMD 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 Slow Embrace: Hemophilia's Gradual Adoption of Gene Therapy

Featuring commentary from:

• Amit Soni, MD
• Steven W. Pipe, MD
• Adam Cuker, MD

The treatment landscape for patients with hemophilia has been enriched with one-time gene therapies, as of the November 2022 United States (US) approval of etranacogene dezaparvovec and the June 2023 US approval of valoctocogene roxaparvovec, both adeno associated virus (AAV) vector gene therapies.

UniQure and CSL Behring’s etranacogene dezaparvovec, marketed as Hemgenix, is approved for treating adults with hemophilia B who currently use Factor IX (FIX) prophylaxis therapy, have current or historical life-threatening hemorrhage, or have repeated, serious spontaneous bleeding episodes. BioMarin’s valoctocogene roxaparvovec, marketed as Roctavian, is approved for the treatment of adults with severe hemophilia A defined as congenital factor VIII (FVIII) deficiency with FVIII activity of less than 1 IU/dL who do not have antibodies to adeno-associated virus serotype 5 (AAV5) according to an FDA-approved test.

Navigating a Novel Therapy Frontier: Gene Therapy's Stunted Impact on Leukodystrophies

Featuring commentary from:

• Alessandro Aiutti, MD, PhD
• Madeleine Powys, MBBS
• Maria Escolar, MD

Leukodystrophies are a group of inherited neurological disorders in which genetic mutations affect the myelin sheath, and are categorized as rare diseases, with a prevalence of around 1 in 7000 live births. Researchers have identified more than 50 types of leukodystrophies, with some common types including adrenoleukodystrophy (ALD), metachromatic leukodystrophy (MLD), Krabbe disease or globoid cell leukodystrophy, and Canavan disease.

Despite their rarity, leukodystrophies are a prime target for gene therapy as most affected patients have a single gene mutation responsible for the disease phenotype. Substantial progress has been made in the field, with 2 gene therapies approved for leukodystrophies in the United States (US) in 2022 and 2024: bluebird bio’s elivaldogene autotemcel (eli-cel/Skysona) for cerebral ALD and Orchard Therapeutics’ atidarsagene autotemcel (arsa-cel/Lenmeldy) for early-onset MLD.

Choosing the Right Treatment Path for Sickle Cell Disease

Featuring commentary from:

• Nicole Verdun, MD
• Haydar Frangoul, MD
• Shalini Shenoy, MD, MBBS
• Vivien Sheehan, MD, PhD
• Akshay Sharma, MBBS
• Alexis Kuhn, PharmD, BCOP
• Mark Walters, MD

The molecular basis of sickle cell disease (SCD), an inherited blood disorder characterized by red blood cells (RBCs) that carry mostly an abnormal form of hemoglobin that sometimes results in sickle-shaped RBCs, has been well-understood since at least the 1950s.^1,2 Despite this knowledge of its pathophysiology, treatment options for SCD were quite limited for many decades afterward. Up until about 10 years ago, the main treatment option for SCD was the small-molecule drug hydroxyurea.

Now, the landscape of care for SCD is rapidly changing. On a single day in 2023—December 8—the field of hematology was shaken by the FDA’s simultaneous approval of 2 gene therapy products for the treatment of SCD: Vertex Pharmaceuticals' and CRISPR Therapeutics’ exagamglogene autotemcel (exa-cel; marketed as Casgevy) and bluebird bio’s lovotibeglogene autotemcel (lovo-cel; marketed as Lyfgenia).

Cell Therapies Hope to Be Next Frontier for Alzheimer Disease

Featuring commentary from:

• Deborah Phippard, PhD
• Paul Y. Song, MD
• Joshua M. Hare, MD, FACC, FAHA

Alzheimer disease (AD) is a growing problem, affecting nearly 7 million people in the United States. In 2021, AD was the fifth-leading cause of death among people aged 65 years and older. Prior to 2023, the field of research for AD had stood relatively stagnant for 10 years until the FDA approved the controversial anti-amyloid therapy aducanumab (Aduhelm).