The gene-editing revolution is jumping from the lab to the marketplace.
The U.S. has approved the world's first medicine employing Crispr technology, a Nobel Prize-winning discovery that promised a powerful new tool for modifying genes to treat disease and improve crop production.
The new treatment, called Casgevy and developed by Vertex Pharmaceuticals and CRISPR Therapeutics, was cleared Friday for treatment of people with the painful sickle-cell disease.
The landmark decision by the Food and Drug Administration heralds a powerful new kind of medicine, one that turns off or replaces genes to tackle conditions that have long confounded doctors and researchers.
Several companies are developing Crispr-based therapies for diseases including heart disease, cancer and rare genetic disorders. Next-generation gene-editing techniques promise to make it easier to administer the therapies with fewer side effects.
How Casgevy works for sickle-cell patients
Sickle-cell disease is caused by an inherited genetic mutation that results in a dysfunctional form of the protein, called hemoglobin, that carries oxygen in the blood.
Casgevy goes after a different gene that, when switched off, allows for the production of a form of hemoglobin that is produced when babies are in the womb that provides a functional substitute for the malformed adult hemoglobin caused by sickle-cell disease.
The therapy's approval "shows the promise of genetic therapies that seek to treat disease at the source by making a targeted change in a person's DNA," said Jennifer Doudna, who shared a Nobel Prize in 2020 for her work helping discover Crispr. "It almost changes the way we define a medicine."
Casgevy is a first step in bringing Crispr-based treatments to patients. Unlike Crispr drugs in development, it gene-edits a patient's cells in a lab, rather than inside a patient's body.
Editing cells outside of the body helps ensure that the therapy doesn't accidentally make changes to other genes that aren't involved in the disease. But it is harder on patients, including requiring them to undergo several days of high-dose chemotherapy to make room for the modified cells.
Casgevy's use, at least initially, will likely be limited. Some health plans might not cover Casgevy because of its $2.2 million per patient price tag. Some patients might be deterred by the weeks they would have to spend in the hospital to get treatment, including the chemotherapy that commonly results in infertility.
"It could be transformative, but it won't be because it's still intensive," said Mark Walters, a professor of pediatrics and sickle-cell researcher at the University of California, San Francisco. "It's also going to be very expensive."
Vertex Chief Scientific Officer David Altshuler said the administration process is intensive and complex, but "we believe that many people will choose that it's worth it for them."
Marie Tornyenu once suffered extreme pain due to sickle-cell disease. After a clinical trial of Casgevy, she no longer feels that pain.
Because of sickle-cell disease, Marie Tornyenu had to be hospitalized sometimes and got monthly transfusions of healthy blood from a donor. She lived in fear of the bouts of extreme pain, usually in her hips and legs. It felt like a "dull ache that just burns and gets exponentially worse," she said.
In 2021, she received Casgevy in a clinical trial after undergoing fertility treatment to preserve her eggs in case she wanted to have children in the future. A few months later, she started to feel like herself again after shaking off the effects of the chemotherapy. Then she realized she wasn't feeling sickle-cell pain anymore.
For the first time, she could take a walk around her neighborhood without getting fatigued. "I still thought about, 'What if I have pain?'" said Tornyenu, 22 years old, of Bethlehem, Pa. "But the pain never came."
Marie Tornyenu had suffered pain in her hips and legs because of sickle-cell disease.
The FDA on Friday also approved a second treatment for sickle-cell disease called Lyfgenia, made by Bluebird Bio, which genetically modifies patients' cells to produce a hemoglobin substitute. Bluebird said it will charge $3.1 million for Lyfgenia.
A fair price for the therapies, given the health benefits they provide, would be between $1.35 million and $2.05 million per patient, according to the Institute for Clinical and Economic Review, a nonprofit that advises insurers and drugmakers on the value of medicines.
Vertex, which will manufacture and market Casgevy, has said it expects Casgevy to be used by patients with severe forms of sickle-cell disease, representing about 20,000 people in the U.S. In a study, 94% of patients went at least one year without having an episode of severe pain requiring medical attention after a single treatment; none was hospitalized.
Sickle cell, which mainly affects Black people, causes severe pain, organ damage and early death. The few available therapies have helped treat complications but not the underlying disease. About 100,000 people in the U.S. have the disease, and more than 20 million people globally have it.
"That the first Crispr-based therapy is in sickle-cell disease is nothing short of extraordinary," said Alexis Thompson, chief of hematology at Children's Hospital of Philadelphia.
How Casgevy came about after Crispr's discovery
The drug's arrival comes just over a decade after the discovery of Crispr, an unusually fast time for basic science research to be turned into a commercial product.
The gene-editing capabilities of Crispr—an organically occurring immune mechanism in bacteria—were described in a 2012 scientific paper by Doudna and Emmanuelle Charpentier.
New biotech companies were soon created to capitalize on the scientific advance, including ones co-founded by Doudna and Charpentier. One of the companies co-founded by Charpentier was Switzerland's Crispr Therapeutics, co-developer of Casgevy.
The scientists shared the Nobel Prize in Chemistry in 2020 for their development of Crispr. The technology's use spread across research labs.
Soon after the seminal Crispr paper was published, scientists at Boston Children's Hospital started using the technology in their sickle-cell research.
The Boston Children's researchers had earlier identified a gene that suppresses the production of a form of hemoglobin that is produced when babies are in the womb. They eventually developed a way to use Crispr to deactivate that gene, allowing for fetal hemoglobin production to restart and provide a substitute for the patient's dysfunctional adult hemoglobin.
Boston Children's Hospital licensed its researchers' patents to Crispr Therapeutics.
"How quickly it's been able to move from just basic science in the lab into a therapy that can hopefully help lots of people is really amazing," said Dr. Daniel Bauer, one of the scientists who made the discovery. "Even to someone who was involved, it would have been hard to predict."