Expert Insights

Expert Insights

Rare Oncology Clinical Trials: The Impact of Gene Therapy

Rare Oncology Clinical Trials: The Impact of Gene Therapy
20 November 2020

As technology rapidly advances, gene therapy continues to evolve and make an increasing impact on research — notably, in rare oncology. But some confusion — and even patient reticence — remains. We are constantly striving to advance the research while also informing and engaging the patient community.

The first step is ensuring clarity between closely related, yet different terms:

  • Gene therapy is the transfer of genetic material, usually in a carrier or vector, and the uptake of the gene into the appropriate cells of the body.
  • Cell therapyinvolves the transfer of cells with the relevant function into the patient.

Further complicating matters, these therapies aren’t exclusive to one another. Some protocols use both gene therapy and cell therapy. In this case, stem cells are isolated from the patient, genetically modified in tissue culture to express a new gene, expanded to sufficient numbers, and then returned to the patient. Diving deeper:

Gene Therapy

The key to gene therapy is engineering a deactivated virus to deliver DNA with a replacement human therapeutic protein — commonly, adeno-associated virus, or AAV. This “new” gene is delivered to cells in tissues such as the heart, brain, eye, or liver. The virus then “disassembles,” delivering the DNA into the cell nuclei. Then, the genetic information from the new gene is transferred into the mRNA. The patient’s body can then begin using this new gene as a “blueprint” for protein production to replicate the therapeutic.

Cell Therapy

While gene therapy does most of its work within the patient’s body, in cell therapy, the patient’s T cells are removed from their blood. The gene for a special receptor — chimeric antigen receptor, or CAR — is inserted into the T cells in a lab. CAR T cells are thus created as the gene encodes the engineered CAR protein on the surface of the patient’s T cells.

After millions of CAR T cells are grown in the lab, the patient is infused with the CAR T cells, which bind to antigens on the cancer cells to destroy them.

FDA Support

The first gene therapy trial procedure was performed in 1990, in which doctors removed white blood cells from patients with adenosine deaminase severe combined immunodeficiency. Lab tests showed 40% improvement; although this was not a cure, and the process must be repeated since white blood cells treated genetically only endure for a few months, the trial was a landmark point for gene therapy.

Currently, the FDA has approved 17 cell and gene therapy products. The EMA has approved 10, of which four were withdrawn between 2014 and 2017 for lack of reimbursement or poor commercial performance.

The FDA remains in close evaluation, releasing several guidance documents over time. The 21st Century Cures Act expedited FDA review for Regenerative Medicine Advance Therapy, specifying:

  • The drug is a regenerative medicine therapy, which is defined as a cell therapy, therapeutic tissue engineering product, or any combination product using such therapies or products
  • The drug is intended to treat, modify, reverse, or cure a serious or life-threatening disease or condition
  • Preliminary clinical evidence indicates that the drug has the potential to address unmet medical needs for such disease or condition

Worldwide, the number of gene therapy trials has rapidly increased; in 2017 and 2018, there were 224 and 232 trials, respectively, compared to 169 in 2015 and 123 in 2016. Cell therapy trials are following suit at an even more rapid pace — in 2015, there were just over 40 trials, while in 2016, there were just under 120.

Moving Forward

Advances continue to accelerate research in these therapies. CAR T therapy is growing increasingly safe and more effective, using gamma-delta T cells that don’t attack healthy cells, and combining with immuno-therapy at lower doses, for example. Beyond safety and efficacy, other challenges remain, such as cost containment and patient burden (such as immunosuppression). There are also regulatory differences that are common with any new therapies, but that also vary between countries. The question of diversity is also a very large focus — are there different results, for example, between races?

Although there are questions that remain with cell and gene therapies, they are undoubtedly going to continue to garner much focus and growth very rapidly over the next decade. If you have any questions, please reach out to our team — we’d love to have a conversation with you!

x

Submit RFI / RFP

By submitting your information to us through this webform, your business details will be added to our database. In accordance with our Privacy Notice, we may then contact you with marketing information about Synteract that might be of interest to you. We will never sell your details to third parties. You can unsubscribe from marketing communications at any time.

Required

x

Contact Synteract

Tell us how to stay in touch with you:

By submitting your information to us through this webform, your business details will be added to our database. In accordance with our Privacy Notice, we may then contact you with marketing information about Synteract that might be of interest to you. We will never sell your details to third parties. You can unsubscribe from marketing communications at any time.

Required

x

 

x

 

x

Download Resource

By submitting your information to us through this webform, your business details will be added to our database. In accordance with our Privacy Notice, we may then contact you with marketing information about Synteract that might be of interest to you. We will never sell your details to third parties. You can unsubscribe from marketing communications at any time.

*Required

x

To complete your download, please choose an option in the Internet Explorer pop-up window at the bottom of this browser.

x

Download Resource

By submitting your information to us through this webform, your business details will be added to our database. In accordance with our Privacy Notice, we may then contact you with marketing information about Synteract that might be of interest to you. We will never sell your details to third parties. You can unsubscribe from marketing communications at any time.

*Required

x

To complete your download, please choose an option in the Internet Explorer pop-up window at the bottom of this browser.

x

Opt In

By submitting your information to us through this webform, your business details will be added to our database. In accordance with our Privacy Notice, we may then contact you with marketing information about Synteract that might be of interest to you. We will never sell your details to third parties. You can unsubscribe from marketing communications at any time.

*Required