From 2014 to 2024: what’s changed in the last decade?

Written by Megan Giboney
CAR-T Cell therapy Clinical manufacturing Clinical trials FDA Gene editing Gene therapy Industry developments News Regulation & policy Stem cells UK and Europe US and Canada

To celebrate RegMedNet’s 10th anniversary, our team has been looking back at how the field of regenerative medicine and advanced therapies has evolved from 2014 to 2024.

Over the past decade, regenerative medicine and advanced therapies have undergone a remarkable evolution over the past decade. In 2014, the field was brimming with promise, but many hurdles —therapeutic development challenges, manufacturing complexities and regulatory uncertainties — stood in the way. Fast forward to 2024, and the landscape has shifted dramatically, with therapies now entering the mainstream.

Cell and gene therapies: from potential to reality

In 2014, the field was still in its infancy, with only a handful of approved therapies and a multitude of experimental treatments. The US Food and Drug Administration (FDA; MD, USA) had approved a handful of cell-based therapies, including several cord blood-based products like Hemacord and Allocord. However, there were no FDA-approved gene therapies at this time [1]. Their first approval didn’t come until 3 years later, in 2017, when the first cell-based gene therapies, Kymriah and Yescarta, were approved by the FDA for the treatment of acute lymphoblastic leukemia and large B-cell lymphoma, bringing gene therapy to the US market for the first time [2,3]. In the same year, the FDA also approved Luxturna, the first in vivo gene therapy [4]. These approvals were major milestones in the field and marked a turning point for cell and gene therapies.

Now in 2024, there are 38 FDA-approved cell and gene therapy products, including six CAR-T cell therapies, treating cancers like lymphoma, leukemia and multiple myeloma. Additionally, multiple gene therapies are on the market for rare genetic disorders, such as spinal muscular atrophy and Duchenne muscular dystrophy [1].

Crucially, the focus has shifted from developing these therapies and proving they can work to refining their effectiveness, reducing side effects and expanding their indications.

Manufacturing: from small-scale to scalable solutions

In 2014, manufacturing was one of the most significant bottlenecks in regenerative medicine and cell and gene therapy development. Producing therapies at scale while maintaining safety and consistency was an enormous challenge. Facilities were limited and the cost of manufacturing therapies, especially autologous cell therapies, was prohibitively high. The challenges of 2014 stemmed from the fact that many of these therapies were personalized, making them difficult to scale. Additionally, the technologies and processes to ensure the consistent production of high-quality therapies were still being developed. As a result, many companies struggled to move from clinical trials to large-scale commercialization [5].

By 2024, substantial improvements have been made in manufacturing technology, which has unlocked new possibilities. Automation, standardization and advances in bioprocessing have enabled the production of therapies at larger scales and lower costs. Moreover, manufacturing processes have become more robust and efficient. Advances in bioreactors, closed-system manufacturing and supply chain logistics have enabled faster and more reliable production of cell and gene therapies. The field has also seen a shift toward digitalization, with artificial intelligence and machine learning playing a growing role in optimizing production processes, monitoring quality control and predicting potential issues before they arise.

These advances have made it possible to produce therapies more quickly and at a lower cost, which is critical as more treatments reach the market and demand increases.

Regulation: from uncertainty to clearer pathways

In 2014, the regulatory landscape for regenerative medicine and cell and gene therapies was highly uncertain. There were no clear guidelines for how to evaluate the safety and efficacy of these therapies, which made it difficult for companies to navigate the approval process. The regulatory frameworks in the US, Europe and other regions were still adapting to the unique challenges posed by these novel treatments.

The FDA had only just begun to develop the regulatory structure that would eventually lead to the approval of breakthrough therapies like Kymriah and Yescarta. Similarly, in Europe, the European Medicines Agency (Amsterdam, Netherlands) was working to establish standards for advanced therapy medicinal products.

By 2024, the regulatory environment has matured significantly. In the US, the FDA has developed clearer pathways for regenerative medicine and gene therapies, supported by the Regenerative Medicine Advanced Therapy designation, which provides expedited review and development support [6]. Similarly, Europe has refined its guidelines for ATMPs, publishing a joint action plan with the European Commission in 2017 to offer more streamlined processes for developers [7].

Although there is still a way to go, the establishment of more harmonized international regulations has helped companies navigate approvals across different regions more effectively. Importantly, the regulatory bodies have also adapted to the growing need for post-market surveillance, recognizing the long-term nature of many regenerative medicine treatments and the need for ongoing monitoring of their safety and efficacy in real-world settings [8].

A decade of transformation

The field of regenerative medicine and cell and gene therapy has seen transformative changes from 2014 to 2024. Once nascent technologies have become viable treatments, manufacturing bottlenecks have been alleviated and regulatory frameworks have evolved to meet the unique challenges of these therapies. While challenges remain, the progress made over the last decade is a testament to the incredible potential of these fields to revolutionize medicine and improve the lives of patients around the world. The next decade promises to bring even more breakthroughs as we continue to unlock the full potential of regenerative medicine and cell and gene therapies.

Source

  1. FDA. Approved cellular and gene therapy products. [Accessed 5 September 2024]
  2. FDA. FDA approval brings first gene therapy to the United States. [Accessed 5 September 2024]
  3. FDA. FDA approves CAR-T cell therapy to treat adults with certain types of large B-cell lymphoma. [Accessed 5 September 2024]
  4. FDA. FDA approves novel gene therapy to treat patients with a rare form of inherited vision loss. [Accessed 5 September 2024]
  5. Salmikangas P, Menezes-Ferreira M, Reischl I, et al. Manufacturing, characterization and control of cell-Based medicinal products: Challenging paradigms toward commercial use. Regen. Med. 10(1), 65–78 (2015).
  6. FDA. Regenerative medicine advanced therapy designation. [Accessed 5 September 2024]
  7. EMA. Advanced therapy medicinal products: Overview. [Accessed 5 September 2024]
  8. Gomes KLG, da Silva RE, da Silva JB, Bosio CGP, Novaes MRCG. Post-marketing authorisation safety and efficacy surveillance of advanced therapy medicinal products in Brazil, the European Union, the United States and Japan. Cytotherapy. 25(10), 1113–1123 (2023).