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From genetic conditions to cancer, the full power of cell and gene therapies (CGTs) is yet to be harnessed. But 2023 saw remarkable progress in that direction, with the momentum continuing into 2024. Despite not yet holding a lion’s share of the market, no therapeutic area is growing as rapidly as cell and gene therapies. Worth US$15 billion in 2022 according to Precedence Research, the global CGT market size is forecasted to be worth US$82 billion by 2032. The overlapping fields of biomedical treatment aim to treat, prevent, or cure diseases, and both approaches have the potential to alleviate the underlying cause of genetic diseases and acquired diseases. The last years have seen considerable progress in cell therapies, particularly mRNA. While the focus on mRNA has somewhat subsided, the field continues to evolve.

As the scientific case for CGTs keeps improving, and with investor support, more products are likely to hit the market in the short term. Of the 14 CGTs that were approved across various therapeutic areas by the FDA over the past decade, 70% were given the green light between 2019 and 2023. There currently are over 694 CGTs in development in the US according to GlobalData’s Drug database. Of these CGTs, 48 assets are in late-stage development (preregistrations and Phase 3).

Oncology will undoubtedly remain the top area of CGT development in the short term at least. Due to high unmet medical needs, oncology is poised to represent 44% of the US$82 billion CGT market by 2032. In oncology, the fundamental concept of adoptive cell transfer involves infusing modified immune cells into patients, empowering their immune systems to effectively combat and conquer a growing range of cancers. Chimeric antigen receptor (CAR) T-cell therapies have pioneered significant advancements in oncology, offering targeted and efficient treatments for certain blood cancers and leukemia. As of 2024, the FDA has approved eight CAR T-cell therapies. Importantly, several of these potentially curative treatments are now being used as second-line therapies. Arcellx is pursuing a cure for cancer through cell therapies. The firm’s lead asset, anitocabtagene autoleucel, is currently in a Phase 2 pivotal trial for patients with relapsed or refractory multiple myeloma. Speaking of the breakthrough potential of the candidate, the firm’s CBO Aileen Fernandes explained: “92% of evaluable patients had a very good partial response or higher, indicating the potential for anito-cel to be a best-in-class autologous CAR-T therapy. Importantly, our therapy demonstrated a unique safety profile with no instances of delayed neurotoxicity or Parkinsonian symptoms, setting it apart from existing CAR-T therapies on the market.”

On the horizon, a highly promising phase 1 clinical trial in Pennsylvania completed in December stands out as the world's first to utilize CAR T cells targeting two proteins linked to the most aggressive form of malignant brain cancer. CAR T cell therapy has revolutionized treatment for many people with blood cancers who had run out of other treatment options, therefore the results of the planned phase 2 portion of the study will be fundamental to understanding how designing CAR affects the way T cells work.

Beyond oncology, cell and gene therapies hold promises in other indications. Non-oncology indications continue to be the most targeted rare diseases by RNA therapies (81%), amongst them Duchenne’s muscular dystrophy, amyotrophic lateral sclerosis, and cystic fibrosis. With three therapies based on RNA editing having entered clinical trials or received the green light to do so in recent months, RNA-editing therapies are picking up steam. Boston-based Ascidian’s RNA exon editing platform is designed to expand the therapeutic possibilities of RNA medicine and treat diseases not addressed by today’s gene editing technologies. As the field cannot (yet) address genes with mutational diversity, Michael Ehlers, CEO and president, explained the firm’s progress: “Our approach enables precise post-transcriptional editing of gene products at an unprecedented scale, resulting in full-length, functional proteins at the right levels, in the right cells. Now, we have reduced that approach to practice and are successfully translating it into the clinic with ACDN-01, the first-ever RNA exon editor to enter clinical development.”

Introducing new genes into existing body cells while keeping them working is a challenging endeavor. Insmed’s RNA end-joining technology allows for the delivery of large genes that traditional gene therapy methods cannot handle. The new platform unveiled in 2023 holds promise for addressing conditions like Stargardt disease, a hereditary retinal condition leading to vision loss usually starting in childhood, which was previously untreatable with gene therapy. In the words of Insmed CEO Will Lewis: “Our research teams continue to advance pre-clinical studies across a range of devastating rare diseases by leveraging our novel gene therapy.”

Democratizing scientific prowesses
Despite the robust CGT pipeline in the US, translating scientific progress into commercial success will remain a challenge. The limited prevalence of certain conditions under study leads to a small patient pool, making it challenging to attain a sizable sample size. Additionally, the view that CGTs serve as treatments only when all other options have failed can deter potential participants. Risk of clinical trial failures – most recently highlighted by the failure of Cleveland-based Athersys’ stroke cell therapy at phase 3 – coupled with high production costs will place further stress on these innovations. On the consumer end, CGTs are amongst the most expensive: the Institute for Clinical and Economic Review (ICER) estimates the average cost of such therapies between US$1 million and US$2 million per dose, with some like Hemgenix (a one-off infusion to treat hemophilia B) costing up to US$3.5 million.

The US government recently established the Cell and Gene Therapy Access Model within the DHHS’ Centers for Medicare & Medicaid Services to help lower drug costs. Effective in January 2025, the Model will test outcomes-based agreements for cell and gene therapies, first focusing on sickle cell disease, which affects 100,000 Americans. Gene therapies for sickle cell disease could be a game-changer for people affected by the condition, along with leading to reducing the hefty costs of treating the disease for both states and taxpayers.

Gene therapies represent a groundbreaking shift in medicine by targeting the root causes of diseases rather than just managing their symptoms. This approach holds the promise of potentially curing previously untreatable diseases, offering hope to millions of people worldwide.