Ensuring Safety as Gene Therapy Continues to Develop Quickly

People with spinal muscular atrophy and other rare conditions with either few or no approved treatments have recently had their hope of a cure renewed by the concept of gene therapy. Basically, gene therapy involves replacing the mutated gene which is causing the body harm with a healthy version. By addressing the root cause of the disorder, researchers believe they can ultimately cure the condition. However, there’s a lot we still don’t know about this revolutionary concept. We’re not clear on the risks, its true safety, or even its longterm efficacy. Since it’s not a reversible procedure, we need to proceed with extra caution.

So how do we move forward to best serve patients? Of course we need to continue to research this potentially life-changing treatment. However, we need to do it in a way that is safe for the very people it’s trying to cure.

An article published in Nature Outlook explains Eric Bender’s perspective on the issue.

First, he discusses who is in charge of regulating the therapy.

Authorities in the field

Ultimately, the safety of gene therapy is monitored by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA). The FDA alone is expected to receive 250 applications this year solely related to gene therapy.

It is the responsibility of these organizations to establish proper safety guidelines and determine which therapies warrant approval. Both agencies have years of experience examining hundreds of studies and speak with confidence in their ability to analyze this new type of treatment. However, they have different procedures for doing so.


Within the FDA, reviewers are grouped into different divisions and the division assigned to a specific treatment follows that drug through its entire cycle. There is some concern that the FDA doesn’t have enough employees to handle the increasing influx of gene therapy candidates. The estimation is that gene therapy applications will reach 1,000 by 2021.

This year, the FDA offered its first draft recommendations for gene therapy according to class of illness. These included rare diseases, haemophilia, and retinal disorders. Currently, approximately 70% of drug applications sent to the FDA are for rare conditions.

The organization also added requirements regarding long-term follow-up for patients in gene therapy clinical trials and frameworks for certain drug manufacturing processes. Long-term follow-up is essential because we don’t yet understand the effects that these therapies may have years down the line. 

“As we treat, we must ascertain that the patient experience — good or bad — must somehow be fed back to decision-makers and contribute to long-term knowledge generation.”

Differently than the EMA, the FDA oversees clinical trials as well as creating these regulatory guidelines.


The EMA Is composed of members from various states in the European Union. All of these committee members have a say in each drugs approval.

To run a clinical trial within the European Union, drug manufacturers must receive approval from the ethics committee of their member state. They also are required to get approval when using a genetically modified organism. The systems for these approval vary slightly within member states.

This year, the EMA reworked its frameworks and guidelines for gene therapy including their design, delivery mechanisms, manufacturing, and characterization.

Truly, it’s about collaboration between both these organizations and the drug manufacturers themselves. The EMA and FDA hold teleconferences regarding gene therapies, and work together to assess the efficacy and safety of new methodologies. Working as partners ensures the best outcomes for the patients these treatments are created to serve.

Ultimately, everyone’s work in this field is data-driven, and as time passes we will gain even more experience and knowledge of gene therapies. Everyone wants gene therapy to succeed, we must simply proceed cautiously.


Many gene therapies use adeno-associated viruses (AAV) to deliver the treatment. However, these viruses have shown an immune response in the liver. While a short-term issue that can usually be handled with steroids, higher doses of treatment may require different approaches. The medical field has a good number of ways to deal with immune response. However, it is essential to evaluate which one of these is best for the individual patient.

Some other things we still don’t know about AAV are- what happens if the patient has already been exposed to AAV previously, and what if proteins created by the gene therapies initiate a reaction in the body because the body?

“In gene therapy in general, we like to believe that we know what the major risks are, but you can never know. Tomorrow, something totally new could come out of the blue. But that doesn’t say that gene therapy shouldn’t be made available to patients.” – Hans-Georg Eichler

It can be very easy to want to speed ahead for trials using novel therapies for rare conditions. But the safety guidelines from the EMA and FDA are simply essential to ensure the patient doesn’t experience additional complications.

The EMA and the FDA encourage drug manufacturers to start communication with them early. These agencies are happy to assist with the designing of trial programs, ensuring safety from the very beginning.

You can read more about this perspective on the development of gene therapies for rare conditions here.

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