With a cost of $2.1 million for a one-dose treatment, Zolgensma is currently the most expensive drug in the United States. Zolgensma treats spinal muscular atrophy (SMA), a genetic disorder that causes muscle wasting and weakness. Although the U.S. Food and Drug Administration (FDA) approved Zolgensma in 2019, some health insurance companies still do not cover it because of the high cost, and others have strict requirements that limit the number of patients who qualify for coverage.
The High Cost of Precision
To understand why a single dose of a drug costs $2.1 million, you have to start by looking at how it is manufactured and why it was created in the first place. Zolgensma falls into the category of personalized or precision medicine because it is a drug that targets specific problems caused by a person’s unique genetic code. Precision medicine is considered to be much more effective for treating diseases than conventional, one-size-fits-all methods.
More specifically, Zolgensma is a type of gene therapy, which means it replaces a faulty or nonworking gene to cure a disease. Zolgensma is designed to target the genetic cause of spinal muscular atrophy, which is a missing or nonworking SMN1 gene. The drug replaces the SMN1 gene with a new, working copy.
However, it is not easy to deliver a working copy of a gene to a cell. The new gene has to be put inside a vector called adeno-associated virus 9 (AAV9). The vector’s original viral DNA is removed and replaced with the working gene, so it does not cause illness. Once the vector enters the body through an intravenous (IV) infusion, it can travel to the cells and deliver the new gene.
Although gene therapy is an effective treatment option and holds the promise of curing many medical conditions, the drug manufacturing process is expensive and difficult. Companies are in a race to develop and market new drugs, yet they have not spent the time to optimize the production process. As a result, drugs are entering the market quickly, but they are very expensive to manufacture, and the high cost is passed down to the patients.
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“There is not enough manufacturing capacity in the world to serve anything but rare or ultra-rare diseases right now simply because of the production process,” explains Eric Hobbs, CEO of Berkeley Lights. “You have to buy very expensive materials to make the drugs for gene therapy, so there is really no scaling up and culturing capability.”
Finding Better Solutions
Unlike antibody therapeutics that allow you to make a cell line to express your products and scale up that cell line into a 10,000-liter bioreactor, gene therapy is hard to scale and very expensive to manufacture. The fundamental problem comes down to biology since the vector starts off as a virus that wants to kill the cells making it. Once the viral DNA is removed and replaced, it is safe to enter a human cell. However, getting to this stage is the expensive part.
Berkeley Lights, a digital cell biology company, is helping to make drugs faster, better, and ultimately cheaper for the patient. Using the Berkeley Lights Platform, the company has shown it is possible to develop stable AAV (Adeno-Associated Viral) and LV (Lentiviral) vector producer cell lines. This means that they have found a more efficient way to make the viral vectors, which are essential for gene therapy.
“Our platform allows you to seed the pens of the chips with all the genes necessary for expressing AAV. But until we add an inducer, it’s not going to trigger AAV expression. We then take advantage of our cloning capability to duplicate that cell,” says Hobbs. “And then we use our tractor beam to essentially stamp daughter cells from one pen to the other. We’ve developed shield technology to protect the parental cell line from the inducer.”
The cells are then exposed to an inducer to trigger viral production, and the cells die. The platform allows you to make a measurement of the actual physical virus that comes from these induced cells in a red channel. In a green channel, you can measure the fraction of those viruses that actually contain the DNA of interest to inject into patients.
“This is one of our quality factors: It’s not enough to produce a large amount of virus. You need a large amount of virus that actually has the payload you’re looking for. So, we’re doing all of those measurements on the chips to ultimately remove that shield technology, and now you retrieve the parental cells that have never been exposed to the inducer and are alive,” says Hobbs.
Producing these types of stable cell lines is a crucial factor in reducing the price of gene therapy and making it more accessible to patients. It can also lead to more research and the development of new therapies for diseases that are more common. Gene therapy has the potential to transform how we treat many medical conditions, but it needs to be scalable and affordable to work.
Thank you to Lana Bandoim for additional research and reporting in this article. I’m the founder of SynBioBeta, and some of the companies that I write about, including Berkeley Lights, are sponsors of the SynBioBeta conference and weekly digest.