Cell and gene therapy: all aboard the rollercoaster ride...

This article is part of our Biotech Review of the Year - Issue 13 publication.

Over the last few years, arguably no other part of the global life sciences industry has shown as much promise, and yet faced as many challenges, as the cell and gene therapy (CGT) sector. CGTs were first conceptualised over half a century ago and have been in development for several decades. However, it was only comparatively recently that Glybera became the first gene therapy to receive approval in Europe in 2012, with Kymriah becoming the first FDA approved CAR T-cell therapy in the US in 2017.

Around this time, the CGT market was undeniably the “hot new thing” and tipped to be the shining light of the life sciences industry, promising long-term patient benefits and even potential cures. However, following the excitement after a flurry of regulatory approvals, a significant number of commercialisation hurdles have, to differing extents, somewhat derailed the sector’s progress. This article explores the current state of the global CGT market (including some of the key challenges faced when bringing such therapies to market) and what its future may hold. 

The state of the current CGT market

Claight’s market research valued the global CGT market at about $21.43bn in 2025 and forecasted an approximate value of $139.83bn by 2034. Unsurprisingly, the US is the leading market for CGT, with the same research finding that of the more than 1,000 companies worldwide operating in the CGT space, over half of them are based in the US. Leading players in the global CGT market include, among others, Amgen, Novartis, Alexion Pharmaceuticals (a subsidiary of AstraZeneca) and Genetix Biotherapeutics (previously known as bluebird bio). However, not to be underplayed, the UK has also long been a pioneering force in CGTs with notable UK success stories including the likes of Autolus Therapeutics, Orchard Therapeutics and Oxford Biomedica. 

Generally speaking, the global CGT market is projected to grow significantly over the next decade – fuelled by both government and private venture funding (albeit acknowledging the turbulent and challenging times for capital markets, and funding for CGTs specifically, over the last few years), supportive regulatory environment and, ultimately, a growing demand for these innovative therapies. Notably, there is a growing awareness that the CGT pipeline is no longer as niche as before, with a focus expanding beyond rare diseases, resulting in an ever-increasing amount of clinical trials for CGTs. To demonstrate this, the American Society of Gene & Cell Therapy reports that there were over 3,000 CGT clinical trials underway globally during 2025. Despite these positive signs and the projections for growth, it is impossible to ignore the many hurdles which biopharma companies face when it comes to commercialising CGTs, which unfortunately threaten the uptake of CGTs and overall success of this industry. 

Commercialisation challenges 

Typically, major challenges for CGT companies arise after obtaining the relevant regulatory approval for their therapy, whereas for many other medicines, this is when the programme is significantly de-risked. 

In some cases, CGTs have been withdrawn, or faced narrowing labels or “black-box” warnings, due to safety concerns. An obvious recent example is Elevidys, which was developed by Sarepta Therapeutics, for the treatment of Duchenne muscular dystrophy. In July 2025, Sarepta temporarily suspended shipments of the therapy due to the death of two patients from liver failure following treatment, and then significantly narrowed its label to reduce the types of patients who could receive the treatment. 

Aside from safety concerns, the other challenges typically faced by CGT companies are commercial and operational hurdles – particularly manufacturing difficulties and supply chain issues, struggles in agreeing reimbursement deals with relevant paying authorities and sometimes also, quite simply, relatively low patient uptake. One of the earliest signs of these challenges for the CGT market was seen in the case of Provenge, a personalized, cell-based immunotherapy used to treat certain types of advanced prostate cancer, which was developed by Dendreon Pharmaceuticals and was, following approval by the FDA, one of the most widely anticipated launches of 2010. However, ultimately this therapy failed due to many of the challenges described above, such as suffering from a complex manufacturing process (which was difficult to scale) and the associated costs of the therapy making it nigh on impossible to obtain reimbursement at a level which the company would consider commercially sustainable. Similarly, a decade on, Zynteglo, which entered the market with a price tag of $1.8m, was withdrawn by bluebird bio (as it was then known) from Europe in early 2022 after failure to agree reimbursement negotiations with German health authorities. 

As a result of these challenges, in recent years, we have seen a number of biopharma companies voluntarily withdraw marketing authorisation for CGTs. A 2024 comparative pharmacovigilance study of CGTs found that, by 30 June 2024, the EMA had approved 26 CGTs, of which seven had been withdrawn – highlighting that withdrawals are now a recurring feature of the European CGT landscape and noting that, as mentioned above, most are attributable to commercial/operational hurdles, rather than solely as a result of product safety issues. The same study noted that while withdrawals are not as commonplace in the US, there has been a general pattern of post-marketing challenges, such as label changes, boxed warnings and trial holds, all of which had a negative impact on the commercialisation of CGTs in the US market. Some companies have even suffered from considerable competition from hospitals which have produced their own cheaper versions of the therapies, taking advantage of hospital use exemptions (or equivalent exceptions) under their local regulatory regime.

In light of this landscape, some biopharma companies have scaled back their CGT programmes or even exited the CGT sector entirely. For example, in February 2025, Pfizer stopped marketing Beqvez (its hemophilia B gene therapy) and said, at the time, that it no longer had any active gene therapy programmes. Similarly, the likes of Novo Nordisk and Takeda have also fundamentally exited the CGT space in recent times and many companies have pivoted away from CGT to double-down on other promising programme areas such as GLP-1 and antibody drug conjugate programmes. Some younger or specialist CGT companies have gone into liquidation or made a voluntary decision to wind down, and many earlier stage biotech CGT companies, particularly those with assets in Phase III trials or approaching commercialisation, have failed to secure further investment. 

However, all is not lost as many large biopharma companies remain committed to the CGT industry and its undoubted potential. To name just a few, Novartis, Astellas Gene Therapies and Alexion have all demonstrated significant expenditure, and success, in new CGT programmes and show no signs of stopping any time soon. Interestingly, many companies in the space appear to be de-risking, and pooling efforts and resources, by way of prioritising partnership deals for CGT programmes. See for example Astellas Gene Therapies’ headline-making deal with AviadoBio in 2024 for AVB-101 (an AAV gene therapy for frontotemporal dementia), which saw reported payments of around $20m equity, up to $30m upfront and potential $2.18bn in milestones. Therefore, while it has no doubt been a challenging few years for the CGT sector, there is a certainly hope for the future – with many biopharma companies (and investors) backing themselves and the industry to overcome these challenging commercialisation hurdles. 

Hope for the future 

Amidst the increasing predictions of a generally improving investment climate in the future, there appear to be a few specific trends or opportunities which offer hope for the CGT industry.

As with seemingly every other industry at the moment, the use of AI offers a seismic opportunity to revolutionise CGTs, particularly in terms of manufacturing, to enable faster, more efficient and ultimately scalable processes. In particular, AI is likely to help automate batch recording and quality control, offer the ability to analyse vast datasets almost instantaneously to better understand complex biological processes and process parameters and, of course, help to identify potential new CGTs earlier and thus expedite the time-consuming and expensive clinical development process. 

Alongside the use of AI, there is an increasing interest in the use of decentralised manufacturing for CGTs. Given the short shelf life of CGTs and the severity of critically ill patients, decentralised models will help simplify logistics and bring manufacturing closer to the patient. The UK’s new decentralised manufacturing framework is addressed by Hugo Kent-Egan in this article.

More generally, the landscape of contract development and manufacturing organisations (CDMOs) in the CGT space is rapidly evolving and expanding. While there are many CDMOs now operating successfully in the CGT space, up until recently, only a limited pool of those could boast of genuine experience of manufacturing for Phase III trials or commercial launch of CGTs. However, over time, one would expect this market up-skilling to occur and ultimately offer biopharma companies greater choice (and, thus, cost efficiencies) when it comes to outsourcing the manufacturing process. We have previously explored the key strategic considerations when partnering with CDMOS for CGT programmes.

As touched on earlier, many CGTs have failed as a result of reimbursement issues given the unparalleled high costs of bringing these therapies to market. Creative payment models are being developed to help address this issue. For example, we have seen annuity-based models (spreading the cost over several years in a pre-agreed payment plan) and outcomes-based models, whereby reimbursement payments are conditional upon the patient reaching specific clinical outcomes by deadlines – although collecting the data on those outcomes can be difficult and costly in practice. However, over the next few years, we expect to see better infrastructure for collecting this data and other creative payment models to emerge and become customary for CGTs - for example, the use of a subscription style model for certain CGTs that allows paying authorities to pay a lump sum for unlimited access to treatments over an agreed period of time. Therefore, greater access to reimbursement coupled with the possibility of reduced costs, arising from efficiencies and growing patient demand, is another source of hope for the CGT sector. 

As well as creative solutions to maximise the efficiency and affordability of existing therapies, in vivo cell therapy has the potential to be a complete paradigm shift for the CGT sector. Traditional ex vivo engineering (whereby a patient’s cells are modified outside the body and reinserted) is labour intensive, costly, complex, time-consuming and requires access to specialised facilities – thus, ultimately, contributing to the cost issues detailed above. However, in vivo therapies, where genetic material or modified cells are delivered directly inside the patient’s body, have the potential to reduce these complexities (and costs) and ultimately expand the scope and availability of CGTs. 

However, a word of caution, while much progress is being shown in this promising area, it is widely acknowledged that a number of technical, safety and regulatory challenges will need to be addressed before in vivo therapies are widely available. Nevertheless, in vivo CAR T-cell therapy, in particular, is rapidly becoming a very hot area for investment, exciting VC investors and large pharmaceutical companies alike. In the last 18 months, companies such as Eli Lilly, Kite Pharma, AbbVie and AstraZeneca have been snapping up companies with in vivo platforms. 

Lastly, for US and European biopharma companies, exploring other territories (in particular China) also offers a new source of hope. In recent years, China has become an increasingly influential market for CGT development, particularly as it is widely viewed as offering quicker and more cost-effective clinical development pathways. Many CGTs are being first evaluated under China’s investigator-initiated trial system, which allows academic centres to run first in-human studies before formal IND/sponsor trials – a trend which is seemingly becoming increasingly popular. 

To conclude, even those with an optimistic outlook would have to acknowledge the difficulties that the CGT sector faces, especially when it comes to commercialisation. However, as we have highlighted, there remain clear reasons to be hopeful for the success of the industry in the future. One thing is for sure, the continued evolution of the global CGT market is set to be a rollercoaster ride for all involved.