CGTLive's Pillars of Progress 2023: Most-Read Features

For all of 2023, the CGTLive^™ team was following along 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.

From major data publications and presentations to FDA decisions and major medical meetings, the team spent all year bringing the latest information to the website's front page.

While speaking to experts in the field or covering the biggest news updates, we identified some recurring themes and concerns that clinicians and researchers had within the field of cell and gene therapy, and wrote deeper dives into these topics than our everyday news coverage.

Some of these features have become our most-read pieces, because of the clinical impact, inventive mechanisms, or other topics they highlighted. Whatever the reason for the attention these stories got, their place here helps provide an understanding of the themes in cell and gene therapy over the course of 2023.

Here, we'll highlight some of the most-read features on CGTLive's cardiology page this year, including features from our new, biweekly Clinical Trials in Progress series. Click the buttons to read further into these stories.

bluebird's HGB-210 Trial Hopes to Support First SCD Gene Therapy Approval

• Lovo-cel, a groundbreaking gene therapy for sickle cell disease, received FDA approval in December, marking a historic milestone.
• Clinical trials reveal Lovo-cel's elimination of severe vaso-occlusive events, supporting its FDA approval for sickle cell disease.
• While celebrating Lovo-cel's approval, experts stress the need to tackle health disparities for optimal patient impact.
  

October 20, 2023 — Prior to the approval of bluebird bio's lovo-cel (lovotibeglogene autotemcel), and CGTLive took a look at the therapy’s turbulent course of development and clinical trials evaluating the therapy for the treatment of sickle cell disease (SCD).

"I do support an approval; I think it's going to be very complicated, because we need to support SCD centers in delivering this product, as well as the product itself... I think it'll be a little bit complicated as we wander into this new territory of high-priced therapies."

– Julie Kanter, MD, of UAB

First in Human: PROCLAIM and upliFT-D Trials Bring Gene Therapy to Frontotemporal Dementia

• Experimental gene therapies, such as PR006 and PBFT02, show promise for treating frontotemporal dementia (FTD).
• FTD lacks approved treatments; gene therapies like PR006 and PBFT02 offer potential breakthroughs.
• Trials for PR006 (Prevail) and PBFT02 (Passage Bio) aim to treat FTD-GRN, a genetic form of FTD.

July 27, 2023 — Frontotemporal dementia (FTD) is the second most common form of dementia and typically affects patients under 65 years of age.1 FTD usually presents in either a behavioral or language variant, the latter of which can cause either a semantic type of dementia or a nonfluent aphasia type. There are currently no approved disease-modifying treatments specifically indicated for FTD

“It's devastating when they get this diagnosis. We have to tell them that there's no potential treatment options—we can only manage the symptomatic symptoms with behavioral modifications or speech and language therapy."

– Rebekah Ahmad, MD, PhD, of University of Sydney

Genetic Medicine in DMD: End Points, Assessment, and Approvals

• Regulators debate microdystrophin as a surrogate endpoint for gene therapy approval in Duchenne muscular dystrophy (DMD).
• Sarepta's delandistrogene moxaparvovec has since been approved; concerns persist over microdystrophin's clinical benefit validation.
• Pfizer and Solid Biosciences also progress in DMD gene therapies; collaboration seeks to address AAV antibody challenges.

June 16, 2023 — While the field of muscular dystrophy has achieved its first approval of a gene therapy, regulators have struggled to come to a consensus on the validity of microdystrophin as a surrogate end point for clinical benefit in pivotal clinical trials in the accelerated approval pathway.

“Several new therapies have been approved by the FDA for DMD using the presence of dystrophin as a surrogate end point. With this as established precedent, we expect additional clinical studies, including ongoing gene therapy clinical trials, to rely on dystrophin as a surrogate end point to predict clinical benefit and therefore potentially receive a marketing approval via accelerated approval from the FDA."

– Paul Melmeyer, MPP, of MDA

Here to Stay: Progress Solidifies the Future of Cell Therapy

• Advances in cell therapies signal a shift towards treating solid tumors, overcoming historic challenges.
• Promising results for afami-cel in recurrent synovial sarcoma showcase potential for engineered T-cell receptor therapies.
• Gradalis’ gemogenovatucel-T and Iovance Biotherapeutics’ lifileucel exhibit efficacy in Ewing sarcoma and melanoma, indicating progress in diverse solid tumor treatments.

April 14, 2023 — For solid tumors, obstacles to bringing effective cell therapies to clinic have left patient populations waiting. Traditional cell therapy approaches, such as chimeric antigen receptor (CAR) T-cell therapies, have so far been unsuccessful in treating solid tumors because of unique challenges in these types of cancers, including tumor heterogeneity, targeting difficulties, and the tumor microenvironment. New treatment development tactics have begun to meet these challenges head on, and with creativity.

“For a long time, we thought that cell therapy was just going to be a hematologic malignancy thing. With the scientific advances in the last couple of years, I think it's very clear that solid tumor cell therapy is here. It's here to stay."

– Alison Betof Warner, MD, PhD, of Memorial Sloan Kettering

After Elevidys: DMD Advocacy Past First Gene Therapy Approval

• Elevidys approval marks 2023 progress in Duchenne muscular dystrophy, but challenges persist.
• Elevidys benefits a narrow age range, highlighting unmet needs for younger and older patients.
• Concerns about gene therapy's efficacy, AAV challenges, and exclusion criteria prompt exploration of new strategies.

December 5, 2023 — Although the road has not been smooth, 2023 was witness to unprecedented progress in the treatment landscape of Duchenne muscular dystrophy (DMD), with the approval of Sarepta Therapeutics’ delandistrogene moxeparvovec (SRP-9001; Elevidys) earlier this summer. Despite the milestone approval, only a small percentage of patients with DMD currently stand to benefit from the therapy. There is much work to be done in the field to improve care for all patients with DMD as well as to answer questions about the gene therapy’s long-term durability, efficacy, and safety.

“We have many people younger than 4 and many people over the age of 5, that are still in need of treatment. So, I think while the landscape is really amazing, and building every single day... time matters to these people. Time means progression of disease."

– Pat Furlong, BSN, RN, of PPMD