The CGT Sector and End of the Year Candies for Children!

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Miguel Forte, MD, PhD
ISCT President
Kiji Therapeutics
Belgium

In several European countries children know that at the end of the year, there is an appraisal on how well they behaved over the past year. It is the tradition of Saint Nicholas and Chimney Pete on the 6th of December. Depending on their “performance” they will receive candies and gifts and celebrate with Saint Nicholas or be prone to less rewarding status with Chimney Pete. Cell and gene therapy is still a child in the therapeutic armamentarium of modern medicine, certainly looking to be a major player in delivering strong value to patients and all stakeholders involved in product development, approval, launch and eventual market adoption and commercialization!

So, how did cell and gene therapy perform in 2025?

The cell and gene therapy field does deserve candies and gifts for the performance in 2025. Despite a tough environment for financing, and several players devoting more attention to other technologies together with the overall challenging macro environment, the resilience of the CGT field and several developments in regulatory evolution, data generation and approvals denotes a strong and growing sector. Interestingly we see some evolutions taking place, like the search for alternatives as options to deal with the challenges, namely alternative funding strategies and geographies for product development.

Key cell and gene therapy (CGT) regulatory milestones in 2025 include multiple new approvals, a trio of FDA draft guidance specifically for CGTs, and major new EMA frameworks for investigational ATMPs and long term follow up. Regulators are both enabling faster, more flexible development and tightening expectations around evidence generation and post marketing data.

Several additional cell and gene therapies reached the market globally in 2025, bringing the total FDA approved CGTs to over 30 by early 2025, with four new global approvals (across FDA, EMA, and other major agencies) reported in Q3 alone. Of note the most recent approval, on the 13th of November, by the European Commission subsequent of CHMP positive opinion of Waskyra, for the gene therapy of Wiskott-Aldrich Syndrome (WAS), submitted by the Fondazione Telethon, showing also the breath and value of new products together with alternative models of product development and application in the C&GT sector¹.

In September 2025, FDA’s CBER issued three draft guidance documents specifically for CGT product development and assessment. On Innovative Designs for Clinical Trials of Cellular and Gene Therapy Products in Small Populations², on Post approval Methods to Capture Safety and Efficacy Data for Cell and Gene Therapy Products³, and an expanded frequently asked questions (FAQ) document on developing potential CGT products⁴. These documents encourage adaptive and Bayesian designs, external controls, and surrogate or intermediate endpoints in rare diseases, while clarifying expectations for post marketing registries, real world data, and long term safety follow up.

Very recently, on the 12th of November, on a NEJM editorial authored by Vinay Prasad and Martin Makary⁵, introduced a proposed “plausible mechanism” pathway to support personalized and ultra rare therapies where traditional large trials are infeasible, reflecting pressure from patient groups to accommodate one off or N of 1 gene therapies. This approach strengthens the confidence on the personalized gene therapy platform approach and is an important evolution of regulatory anticipated practice.

On the EU side, a key 2025 milestone is the EMA Guideline on quality, non clinical and clinical requirements for investigational ATMPs⁶, coming into effect on 1 July 2025 and aiming to harmonize expectations across vector, cell, and tissue engineered products in early stage development. This complements EMA’s evolving ATMP action plan and updated advice on safety, efficacy follow up, and risk management, which focus on structured long term monitoring of treated patients⁷. It should also be stressed that the authorities and the public sector are making efforts to support biotech in general and in particular the CGT sector as source of innovation and value. The expressed intention by the European authorities through the biotech act⁸, just gone through public consultation and planned for publication late in 2026 is in line with this intention!

Interestingly a couple of evolutions over 2025 deserve mention and should be followed going forward. On one side, companies and product developers are looking into alternative models of funding while also exploring new geographies for business development also with possible new models of engagement.

The traditional venture capitalist investment becoming more risk averse, particularly at the early stage of start-up creation before clinical data de-risking, is leading to alternative funding approaches with an increase in licensing and co-development deals. A clear example is the deal between EsoBiotech, a Belgian start-up for in vivo CAR-T and Pregene for a co-development agreement⁹ that eventually led, in 2025, to an acquisition of EsoBiotech and the in-vivo asset by Astra Zeneca¹⁰.

The deal also highlights another trend of the geographic migration of the center of activities in CGT with an expanding activity in Asia, in particular China. In fact, the last sector analysis indicated that the number of companies in the C&GT sector and the number of active clinical trials in Asia have overtaken the United States¹¹ and some predictions indicate that the number of clinical trials, including IITs, will continue to grow in Asia ahead of the other regions.

Towards the end of the year of 2025, we have been seeing an improvement in interactions between academics trying to move the translation of their projects and companies recognizing some traction in discussions with potential partners, both venture capitalists as well as the growing activity in licensing, co-development and straight merge and acquisitions. That sense of realistic optimism has been with us before but some of the financial indexes gives us confidence that, albeit slow, the recovery (to a balanced equilibrium and growth) is really coming!

The regulatory evolution is underlying the growing maturity of the sector and parallels some of the results in the field, supporting the value of CGT, and the impending optimism mentioned above. It indicates also, a strong commitment of the regulators to guide, learn and collaborate with CGT product developers to facilitate the approval and reach of innovative and value adding products to patients with unmet medical needs. This evolution, together with some signs of financial recovery and investment willingness, plus public sector commitment to foster biotechnology and CGT products within that, gives us a rewarding feeling for 2025, allowing for the candies, a sense of commitment resilience and hope for the year of 2026. It will be important to follow these trends, namely the growth of CGT in different geographies and the attitude of investors towards financing early stage of the translation of innovation into products going forward into 2026!

For 2025, I would give the CGT sector the opportunity to celebrate growth and expect further growth going forward. Candies should be given, for the resilience as well as several achievements. We all would like more, and should work towards more growth and achievements, understanding that the environmental conditions are tough but the value proposition is strong requiring commitment and focus!

As we move into the new year, I invite you all to make sure you come to the ISCT annual meeting in May 2026, taking place in Dublin, where we will review the status of the field and for sure continue to look forward to see value being brough to patients, the strengthening of the sector, new innovation and possible new news and practices that will be worth us listening through the program or discussing around our round tables.

Counting on your participation to the next ISCT annual meeting and the discussions.