Pivotal Cell And Gene Therapy


Mainstreaming cell and gene therapy clinical trials

Cell and gene therapies (CGT) are starting to live up to their promise, not only to create treatments for previously untreatable diseases but also, in some cases, to provide actual cures. The first cell therapy, Novartis’ Kymriah, a CAR-T treatment, was approved1 in 2017 for relapsing and recurring diffuse large B-cell lymphoma, but it has added additional indications. The same year, the first gene therapy, Spark Therapeutics’ Luxturna, was approved2 to treat retinal dystrophy caused by biallelic mutations in the RPE65 gene. The mRNA COVID-19 vaccines developed by Pfizer-BioNTech and Moderna also fall into the category of CGT.

This article looks at the CGT landscape, the challenges biopharma companies face in running clinical trials and tips on how to surmount those obstacles.

Sponsored by ICON

Mainstreaming cell and gene therapies

Development, manufacturing, regulation and market access

Read the whitepaper

Brief overview of the CGT landscape

A useful starting point is to understand the different types of CGTs. The following are the definition of the three types:

  • Cell therapies: involves the transfer of intact, live cells into a patient to treat or cure a disease (autologous: from the patient; allogeneic: from a donor). CAR-T therapies fall into this category.
  • Gene therapies: the transfer of genetic material to prevent or treat disease; this genetic material changes how a cell manufactures a single protein or group of proteins.
  • mRNA vaccines. These broadly fit into the CGT category, such as the COVID-19 vaccines from Pfizer-BioNTech and Moderna, as well as other mRNA-based therapies being developed.

The FDA has approved 24 CGTs3 in the U.S. In the first half of 2022 alone, the FDA approved two CAR-T therapies for blood cancers for earlier-line treatments, making a total of six CAR-T therapeutics available in both the U.S. and the European Union.4 The European Commission approved PTC Therapeutics’ Upstaza, a gene therapy for a rare genetic nervous system disorder, aromatic L-amino acid decarboxylase deficiency and BioMarin’s Roctavian, a gene therapy for Hemophilia A. In August, the FDA approved bluebird bio’s gene therapy, Zynteglo, for beta thalassemia.

According to the Alliance for Regenerative Medicine,4 13 CGTs are up for FDA decisions in 2023, with an additional three in Europe. And per the Milken Institute, 50 to 75 CGTs are expected to be approved in the U.S. by 2030.5 Despite these advances, CGT is still an extremely cutting-edge science, with numerous obstacles to becoming less ultra-niche-oriented and more mainstream.

Navigating some of CGT clinical trial complexities

Broadly, sponsor companies face three challenges when running CGT clinical trials. They are:

  1. Complexity of trial design and lack of experience with CGT trials.
  2. Constraints on manufacturing capacity.
  3. Recruitment and retention of participants.

Complexity of trial design and lack of experience with CGT trials

Because CGTs are so new, regulators, sponsors and trial sites have relatively little experience conducting clinical trials in this space. As a result, standardized approaches are still being developed.

As CGT research expands beyond immuno-oncology, Tamie Joeckel, global business lead for ICON’s Center for CGT noted that it is becoming increasingly common to engage with sites that have never handled cryopreserved IP and don’t have access to on-site cryostorage for multidose therapies.

Joeckel added that another significant challenge occurs when sites participate in multiple trials and work to manage multiple protocols that have specific handling and documentation requirements. This reinforces the industry’s need for detailed site evaluations, process mapping and ongoing site staff training and the need for continued work on industry standards.

As a solution, Joeckel recommended mock runs as part of site readiness to map out the end-to-end workflow ranging from product receipt through thawing, dosing, etc.

Constraints on manufacturing capacity

While several of the larger CDMOs continue to invest and expand in CGT facilities, in recent years, numerous biopharma companies have invested in manufacturing facilities for gene and cell therapy vectors, either by building their own or acquiring CRMOs focused on it.  While the industry continues to move to “off-the-shelf” solutions with allogeneic therapies derived from healthy donors, a large reason for capacity constraints is the autologous therapies that use the patients’ own cells to manufacture a single dose and can take 12 to 20 weeks to produce.  In October, Allogene became the first company to receive FDA approval to start the first Phase 2 clinical trial in large B-cell lymphoma (LBCL).

Slot allocation and capacity are well-known bottlenecks, although companies work hard to mitigate them. A study from Industry Standard Research6 reported that CGT manufacturing outsourcing is expected to decrease from 44% to 21% over the next few years, particularly as products approach commercialization.

Sponsored by ICON

Mainstreaming cell and gene therapies

Development, manufacturing, regulation and market access

Read the whitepaper

Several organizations, including the American Society of Gene & Cell Therapy and the Advanced Robotics for Manufacturing Institute, have partnered with industry to focus on automation and closed systems, with the goal of improving manufacturing efficiency and scale. Meanwhile, drug developers need to plan ahead and develop strategies to scale up for eventual commercialization by choosing the right partners to provide enough high-quality materials for each stage of the clinical trial process and possible market entry.

Joeckel noted that, while courier and shipper technologies now offer excellent solutions transporting the IP to the sites, she encouraged sponsors to focus on the “last 100 yards” of product handling and quality control following the delivery.  Integrating site-specific procedures into the protocol is required to document the chain of custody, chain of condition and chain of identity for the therapies in question.  Additional considerations are coordination between multiple departments for the receipt, inspection and quality approval for shipments and appropriate cryostorage facilities. Often, these are effectively allocated to staff specifically trained in the protocol requirements.

Recruitment and retention of participants

Recruitment and retention of clinical trial participants are challenging for almost all indications and treatment modalities. CGTs have some unique characteristics. One is simply that many of the diseases for which they are being developed are rare, where there are relatively few patients and they’re typically spread out geographically. Another is that because the therapies are so new and complex, longer-term follow-up studies are often required. Sponsor companies are advised to embrace early engagement, data presentation and partnering with physicians and patient advocates.

Finding the Right Partner

Gene and cell therapies are here and promising to deliver not just treatments but also, in some cases, cures. There are numerous challenges to working in this field, ranging from lack of experience in the space to manufacturing bottlenecks and patient recruitment and retention. Sponsor companies are well-advised to seek out CROs that can help guide them through the intricacies of CGT development, moving from a strictly contractual relationship to a more consultative relationship. But with the right partner, gene and cell therapies can be a path to a new age of medicine.

To learn more about how ICON can help you throughout your entire drug development process, visit https://www.iconplc.com/contact/enquiry-form/ today.


  1. “FDA approval brings first gene therapy to the United States.” U.S. Food and Drug Administration. Aug. 30, 2017. https://www.fda.gov/news-events/press-announcements/fda-approval-brings-first-gene-therapy-united-states
  2. “FDA approves novel gene therapy to treat patients with a rare form of inherited vision loss.” U.S. Food and Drug Administration. Dec. 18, 2017. https://www.fda.gov/news-events/press-announcements/fda-approves-novel-gene-therapy-treat-patients-rare-form-inherited-vision-loss
  3. “Approved Cellular and Gene Therapy Products.” U.S. Food and Drug Administration. Aug. 17, 2022. https://www.fda.gov/vaccines-blood-biologics/cellular-gene-therapy-products/approved-cellular-and-gene-therapy-products
  4. “Regenerative Medicine: The Pipeline Momentum Builds.” Alliance for Regenerative Medicine. September 2022. https://alliancerm.org/sector-report/h1-2022-report/
  5. “Cell and Gene Therapies: Looking Ahead to 2022.” Milken Institute. https://milkeninstitute.org/report/cell-gene-therapies-2022
  6. “Cell & Gene Market Outlook.” ISR Reports. April 7, 2022. https://isrreports.com/cell-and-gene-market-outlook/
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