Cell and gene therapy products: what is an ATMP?

If you were to see the phrase ‘Advanced Therapy Medicinal Product’ (ATMP) you might guess, ‘an advanced treatment that is a medicine?’ but you will not get much more from this without doing a lot more homework.

What is an ‘Advanced Therapy Medicinal Product’ (ATMP)?

Whoever decided that cell and gene therapy products should be described as ‘Advanced Therapies’ was a little short sighted as to how this phrase would age and strangely so, once the phrase was coined and used by the FDA (note that the FDA has RMAT designation) it has been picked up and used all over the world. This is a bit of a disaster from a communications perspective for a society familiar with terms including ‘stem cells’, ‘gene therapy’, ‘ cell therapy’, ‘tissue engineering’, all now being lumped to some extent under the banner ‘Advanced Therapies’. But, so it is and so we go forward. Now our focus is just to understand what Advanced Therapy Medicinal Products are and what they can offer!

ATMPs are ‘next generation’ pharmaceuticals based on cells, gene therapy or tissue replacement. These pharmaceuticals offer novel technologies for new options for disease treatments. Where no treatment or no cure was available for a disease ATMPs may open new doors to enable:

• Curing disease by replacing diseased cells/tissues or correcting diseased genes
• Treating disease by adding cells or genetic material (DNA/mRNA)
• Removing defective cells by programming the body to attack them

You can find a more ‘technology’ based classification at the end of this article.

Examples of ATMPs

You may have heard of some ATMPs – CAR T (Yescarta, Kymriah), Luxturna gene therapy for blindness, Strimvelis gene therapy against ‘bubble boy’ syndrome. These cell or ‘recombinant’ (cut-paste) gene-based pharmaceuticals are revolutionizing treatments around the world and it is only early days. Patients who had no treatment options or patients who had exhausted all treatment options are finding new hope in ATMPs and many lives have been saved or transformed already. This field is moving incredibly fast; all of the major pharmaceutical companies have programs in ATMP. Interestingly, the COVID19 vaccines developed by AstraZeneca/Oxford, Pfizer/BioNTech, Moderna and Janssen are based on delivery of the same recombinant (cut-paste) gene technologies as some gene therapy ATMPs but the recombinant genes delivered for ATMPs introduce disease free human gene sequences to patients instead of coronavirus spike proteins.

The coronavirus pandemic is greatly accelerating capabilities of National healthcare agencies and clinics to be able to handle ATMP type technologies and treatment of basically the entire world population with such technologies is going to create unprecedented data on their safety. The Coronavirus pandemic is no doubt accelerating the ability to treat patients with untreatable or uncurable disease by at least 10 years.

ATMP World Tour

Around the world promising initiatives to address the challenges of developing these complex gene and/or cell based pharmaceuticals have been popping up and rapidly developing in the last 10 years. Some well known examples include the British Cell and Gene Therapy Catapult, the Centre for Commercialization of Regenerative Medicine (CCRM) and the ‘ATMP Sweden’ National Initiative. The breadth of need is extensive and unprecedented interactions required between pharmaceutical companies, hospitals, researchers and national authorities mean that technology is arguably right now not always the greatest challenge. There are many potential therapies trying to make their way to patients but the foundations for inclusion of these therapies in our society need to be worked out. How will we pay for an ungodly expensive therapy today that cures a patient in one treatment instead of treating this patient with a relatively cheap (or expensive) pill that they need to take every day for the rest of their life? In the end the curative therapy will be cheaper for society but the models on which our healthcare is based are not built with this type of opportunity in mind. A nice summary of the ‘non-tech’ challenges in ATMP development can be seen in the program of the ATMP world tour April 26-30, 2021, where world leaders are coming together to discuss their approach to solutions. ATMP – ATMP world tour 2021 (atmpsweden.se).

You may also find a video by the European Medicines Agency on ATMPs to be useful (below).

For those who want to go deeper into this topic of what ATMPs are from a technology or regulatory perspective this resource may also be useful ATMP – What are ATMPs? (atmpsweden.se), including the Q&A to clarify what therapies are and are not regulated as ATMPs.

ATMPs and cell therapies

It is important to understand that ATMPs are pharmaceuticals or drugs, not all ‘cell therapies’ are ATMPs. For example, a blood transfusion is a cell therapy but it is not a pharmaceutical so it is not an ATMP. Why is it not a pharmaceutical? The cells used for a blood transfusion have not been modified and will do the same job they did in the donor, thus this is just a transplant and the treating doctor is responsible for ensuring the safety and efficacy of the treatment is sufficiently risk free to benefit the patient. For more complex cell therapies , where manufacture is required or where cells are transplanted to a different organ, external and independent oversight is needed to ensure that these treatments have suitably low risk and sufficient benefit to the patient. These complex treatments are regarded as pharmaceuticals (i.e. drugs) and regulated by National/Regional public health agencies (FDA/EMA) who ensure the safety, efficacy, and security of these drug products. These treatments are now obliged to comply with Good Manufacturing Practice and undergo clinical trials towards market approval. This is EXPENSIVE and thus why many ‘cowboys’ are trying to get around their treatments being classified as an ATMP as they do not want to spend their profits on proving it works or is safe if they can just buy a boat instead. Even if it did work, cowboys may treat a few thousand patients in their lifetime but a product that can be industrially produced and proven to be safe and efficacious could effectively treat millions.

We are imagining a healthcare future where we can modify a patient’s genome, replace diseased cells or tissues and/or selectively attack and remove defective cells. This is not a game. This is the reality of patients’ lives. Opportunities need to be brought forward ethically and safely. Today we can give a functional immune system to a baby born without one, and bring a terminally ill cancer patient into remission, but the potential in this industry to specifically target defective cells and genes, instead of pumping the whole body with drugs or radiation, means that in the next 10-20 years we will be looking at a very different approach to healthcare. Everyone is pepped for this, the patients, the doctors, the nurses, the caretakers. There are so many opportunities for new patient treatments that industry are working together to get this moving.

This is truly an exciting space to watch!

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References

1. Advanced therapy medicinal products: Overview | European Medicines Agency (europa.eu)
2. ATMP – What are ATMPs? (atmpsweden.se)
3. Summaries of scientific recommendations on classification of advanced therapy medicinal products | European Medicines Agency (europa.eu)

Advanced Therapy Medicinal Products (ATMP) – pharmaceuticals based on:

• Technology to modify patient genome
• Recombinant nucleic acids or genes
• Substantially manipulated cells
• Cells intended for a non-homologous function
• Engineered tissue