It usually takes time for scientific discoveries in the lab to make their way to the market.
The groundbreaking gene-editing technology known as Crispr, which acts like a molecular pair of scissors that can be used to cut and modify a DNA sequence, has moved rather quickly from the pages of scientific journals to the medical setting. Earlier this month, about three years after Jennifer Doudna and Emmanuelle Charpentier won the Nobel Prize in Chemistry for describing how bacteria's immune system could be used as a tool to edit genes, regulators in the U.K. approved the first Crispr-based treatment for sickle cell disease and beta-thalassemia patients. The treatment, from Vertex Pharmaceuticals and Crispr Therapeutics, could be approved by the U.S. Food and Drug Administration early next month for sickle cell patients.
While many obstacles lie ahead for the nascent field, such as how to pay for treatments that typically cost more than $1 million, these regulatory approvals are just the start as newer gene-editing technologies such as base and prime editing make their way through human studies. In an interview, Prof. Doudna says the approval is "a turning point in medicine because it really shows how genome editing can be used as a one-and-done cure for disease."
Gene editing is part of a broader therapeutic revolution that encompasses genetic and cellular medicine. The pills and injections we are all familiar with generally target proteins or pathways in the body to treat disease. With gene and cell therapy , we can now target the root cause of disease, sometimes curing patients.
One reason Crispr has moved so fast is because it is a relatively easy tool to use. As soon as it was discovered, people around the world began adopting it for their application of interest, explains Doudna.
Additionally, she says, the technology was timely. "We had a lot of information about genes. We had the ability to synthesize genes and even whole segments of genomes," she says. "What we didn't have at the time was a tool that we could use to rewrite genomes. And that's what Crispr provided, so it was kind of almost like the missing piece in that whole ecosystem."
Wall Street is excited about the field's long-term potential, too, even as billions of dollars have been erased from the sector's market value the past two years as rising interest rates hammered small biotech companies—especially those with moonshot ideas. With some of the top companies such as Crispr Therapeutics and Intellia Therapeutics trading at more palatable valuations relative to their 2021 highs, that presents investors with opportunities. Big Pharma has also started jumping into the fray. In the latest significant deal for the field, Eli Lilly agreed last month to spend up to $600 million to acquire certain rights from gene-editing company Beam Therapeutics.
The road to blockbusters will be challenging, though, with safety and reimbursement concerns top of mind. And, as is often the case, the first drug to market isn't necessarily the best or most lucrative.
For the Vertex/Crispr treatment, the process is known as ex vivo, meaning cells need to be collected from the patient, shipped to a manufacturing facility, genetically manipulated in the lab using Crispr and shipped back to the hospital. Importantly, the patient needs to receive chemotherapy before the cells can be reinfused, which carries the risk of causing infertility. It is also likely to face competition. Later in December, the FDA could approve a gene therapy from Bluebird Bio for sickle cell patients.
"From a medical and scientific standpoint, it's incredibly exciting," says Janus Henderson portfolio manager Daniel Lyons. "But you do have to be somewhat cautious when you think about how many patients are going to be willing to go through what essentially is a stem cell transplant procedure to get this kind of curative therapy."
RBC analyst Luca Issi says that in vivo Crispr therapies, which are delivered directly to the patient, hold more appeal to investors compared with ex vivo therapies like Casgevy. Intellia, co-founded by Doudna, is the furthest along with an in vivo therapy. It is conducting a late-stage study for a disease known as ATTR. The therapy is intended to knock out a gene in the liver to ultimately drive a cardiac benefit.
"It's a simple infusion that edits a specific gene in the liver," says Issi. "There are no cells that need to be collected, no cells that need to be shipped, no cells that need to be manipulated in a lab and shipped back and, importantly, no chemotherapy or risk of infertility."
Intellia and other competitors are targeting the liver for a reason. "This is an organ easier to target as it serves as the filter of our body so a simple intravenous infusion can be really effective," he says.
Longer-term, gene editing will have to find ways to get to harder-to-reach tissues and organs if it is to expand its potential for curative therapies. Doudna mentions cancer and Alzheimer's as exciting areas for development in the longer-term.
"Could we protect people who have a genetic susceptibility to Alzheimer's from getting it by using Crispr to alter the genes that might be causing that predisposition, and doing it early, before somebody is already kind of in the throes of dementia?" she wonders, citing recent studies. "I think that's a very interesting direction."
We aren't there yet, but clearly this is the first chapter of what is surely to be a new era in medicine.