Decentralization of genetic medicine

9-6-21/Kevin Curran

Our world is being rapidly decentralized. We are watching this happen with media, currency and work from home.

Yet, medicine remains strongly centralized.

In the U.S., the FDA regulates our industry with strong federal control.

Most drugs are brought to market by enormous pharmaceutical companies. The drugs are produced in large manufacturing centers and distributed out to hospitals. Clinical trials required for FDA approval are expensive, but if a drug is approved the company will set a high price and recoup investment. This system has been working for the most part. But…how will this change as we travel farther down the road of personalized medicine?

Since we decoded the human genome in 2003, there’s been a strong trend towards personalized medicine. The patient’s DNA sequence is often an important criteria when physicians decide who is eligible for one particular drug. Cell therapies for lymphoma now require a customized, genetically re-engineered, cellular product to best treat the cancer patient (CAR-T).

I think it is highly likely the pharmaceutical industry will move towards greater decentralization as we attempt to keep up with this movement towards personalized medicine.

What would decentralized medicine look like?

Cell and genetic therapies could be designed and manufactured on site at regional hospitals or a local biomanufacturing sites. This would eliminate a lot of time and costs spent shipping items around the country. The patient specific component to the medicine can be readily incorporated into the drug, since the drug could be designed down the hall from the patient.

We are still getting over the hump of efficiently manufacturing cell and gene therapy products from centralized sites. But this technology will soon become as routine as chemotherapy or a bone marrow transplant. When these techniques become safe, reliable and automated, there’s no reason why we can’t produce and deliver this life changing medicine from regional health care locations. This trend is already underway with CAR-T cancer therapy. Academic hospitals are producing their own genetic medicine for lymphoma patients via on-site manufacturing departments.

‘The future is already here – it’s just not evenly distributed.’ ~ William Gibson

Gene therapy has arrived but it’s not readily available.

We will likely see 20-40 new genetic medicines approved in the US in the next decade. Many of these medicines will treat various cancers via genetic engineering of a patient’s immune cells.

Five of these gene therapies for cancer have already become commercially available in the US. The cancer patient’s immune cells are removed from their body and genetically modified in a laboratory. Once genetically engineered to hunt down tumors, the enhanced immune cells are infused back into the patient’s blood.

In terms of price-tag…..cancer drugs tend to be quite expensive and these gene therapies are no exception.

Governments struggle to cover the costs of these drugs. Even developed nations are balking at the price of sophisticated gene therapies. European nations recently told a gene therapy company they will not pay the requested price tag for a drug called Zynteglo. The gene therapy company, named Bluebird Bio, asked European nations to pay $1.8 million/patient to treat an inherited blood disorder. Germany and other European nations countered with a lower price and, in response, Bluebird Bio walked away from the negotiating table.

As it stands now, European patients suffering from this blood disorder (beta-thalassemia) do not have the option to receive this potentially curative gene therapy.

The technology is here…it’s just not evenly distributed.

How do we remedy this?

We can try to fix this problem within the box or outside of the box.

Inside the box: 

1. Link pricing to quantifiable health benefits (QALYs)
2. Prevent pharma companies from billing for procedure until after benefits are observed.
3. Spread the cost of gene therapy across 4-5 years.
4. If a second dose is required, ensure company offers a free re-dose or offers re-dose at severely reduced price.
5. Prevent company from raising price more than pace of inflation.

Outside the box:

1. Governments step in and become manufacturers of cell and genetic medicine. This may be appealing option for therapies that move off patent.
2. Broaden the ability of clinical trials to treat patients with unapproved medicine.
3. Offer approved genetic medicine at a highly reduced price if durability of benefit remains unproven in clinical trials. In this sense, the customers are helping to fill in the durability data.
4. Nations with less stringent regulatory structures can increase their capacity to deliver genetic medicine.

I’m in favor of decentralizing genetic medicine. Many of the outside the box remedies play into the broader concept of decentralizing genetic medicine.

As mentioned, a decentralized approach could provide an ex vivo, genetic therapy to a patient without the involvement of a large pharmaceutical company. The therapy could be administered in a manner and reimbursement channel similar to a bone marrow transplant.

Infrastructure: The gene therapies I mentioned above can be developed within cell manufacturing facilities that already exist in many large academic hospitals. If a hospital contains a bone marrow transplant unit, then the hospital already has some infrastructure to build upon for the manufacture of ex vivo gene therapies.

Intellectual property: Many components of gene therapies are protected by patents from the originator company. That said, the DNA sequence of a gene is not patentable and many components of the genetic vector that delivers the therapeutic gene are also public domain. IP is a challenge but it’s not a roadblock.

Regulations: Regulatory approval is another tough nut to crack. On one hand, it is obviously important to properly test drugs before heading to market. On the other hand, a FDA approval often costs originator companies 1-2 billion dollars. Investors want to see a return on that investment…hence enormous price tags. However, it is possible to utilize clinical trials in the U.S. as a means to distribute medicine and also, other nations have less stringent regulatory hurdles to clear for approved drugs.

Thanks for following along. In upcoming articles, I’ll continue to explore this topic of decentralized medicine.

Further reading:

Here is my review article on CAR-T and the allogenic option for CAR-T. CAR-T is the name of the gene therapy discussed above for cancer patients.

This paper further explores decentralized medicine.

Authors of this paper provide a list of costs necessary for a hospital to develop their own cell therapy manufacturing unit.