The World’s First Crispr Drug Gets a Slow Start

The first medical treatment to use Crispr gene editing has been on the market for a year. Its complexity means few patients in the US have received it yet.

Deshawn “DJ” Chow waited a year to receive a treatment that could change his life. The 19-year-old was born with sickle cell disease, which makes his red blood cells crescent-shaped and sticky. The misshapen cells build up and block blood vessels, cutting off oxygen to parts of the body and causing episodes of excruciating pain. The condition affects about 100,000 people in the United States, most of them Black.

The pain came more and more frequently for Chow in high school, landing him in the hospital often. He missed school, birthday parties, and sleepovers with friends. Sometimes, the pain lasted for days. “It’s like my body is on fire,” he says.

A year ago, he found out about a new treatment called Casgevy that could end his years-long battle with pain. It’s the first approved medicine to use the Nobel Prize–winning technology known as Crispr, a type of gene editing. Chow received Casgevy on December 5 at City of Hope Cancer Center in Los Angeles. He is among the first patients in the US to get the treatment since its approval in December 2023. It was also approved for beta thalassemia, a related blood disorder, this January.

Due to manufacturing complexities, insurance delays, and the extensive preparation involved for patients, few individuals in the US have been dosed with Casgevy since it became commercially available. The slow rollout underscores the complicated nature of commercializing cutting-edge medical treatments and getting them to patients. Another genetic treatment for sickle cell, Lyfgenia, won approval last December, and the first patient was treated in September. Made by Bluebird Bio, it uses an older technology that introduces a new gene to treat the disease.

Vertex Pharmaceuticals and Crispr Therapeutics, which developed Casgevy, have not publicly said how many patients have received the therapy so far. WIRED reached out to all 34 US hospitals approved to administer it as of December. Of the 26 that provided answers, only City of Hope and Children’s National Hospital in Washington, DC, said they had administered Casgevy. (Three hospitals declined to comment, and five others did not respond to multiple inquiries.) Chow is City of Hope’s first sickle cell patient, while a beta thalassemia patient has been treated at Children’s National. Several authorized centers told WIRED they will begin infusions of Casgevy in early 2025.

“The process of getting this drug is very different from just taking a pill,” says Leo Wang, Chow’s hematologist-oncologist at City of Hope. It is a one-time therapy that involves collecting and editing a person’s stem cells. For the patient, it means a harsh round of chemotherapy before getting the cells, and a month in the hospital afterward.

It’s an arduous but transformative treatment. Among 42 patients who received Casgevy in clinical trials, all but three have been free of pain crises for at least a year, according to new data from Vertex. The average length of time without pain crises for those treated is more than two and a half years, with some participants going on five years.

“There’s a lot of interest and a lot of hope,” says Edward Donnell Ivy, chief medical officer of the Sickle Cell Disease Association of America. “We’re at the dawn of a new age for sickle cell disease.” But this hope and interest isn’t translating into a rush of demand yet.

Trusting the (Lengthy) Process

Chow and his parents had heard about Casgevy’s approval and reached out to City of Hope, which was among nine centers to initially offer the treatment. They learned about the risks and side effects and understood that getting the therapy would mean a lengthy hospital stay. Still, Chow was ready to move forward.

For other patients though, the decision isn’t as easy. There is wariness about new technology that involves manipulating genes, and many Black patients have had negative interactions with the health care system because of historical bias and discrimination. “The medical establishment has a long legacy of earned mistrust with minoritized populations,” Wang says.

Many patients also don’t realize that receiving Casgevy involves such a lengthy process. “They don’t necessarily know that it looks and feels like a stem cell transplant,” says Wang. “They can be taken aback.”

Bone marrow or stem cell transplants can cure sickle cell disease and have been available for decades. Like Casgevy, they require chemotherapy and several weeks of hospitalization, except the stem cells come from a donor. Patients need a close genetic match in order to get a transplant, and only a fraction of sickle cell patients have an eligible donor. Casgevy offers a future free of pain crises to far more patients.

Chow first met with doctors at City of Hope in March. Once his insurance approved Casgevy in May, his doctors could begin collecting his stem cells. Patients take a mobilization medicine that moves their blood stem cells from bone marrow into the blood stream. A machine then collects and separates the blood stem cells in a process called apheresis.

“The collections themselves are a very complex process,” says Julie-An Talano, a pediatric hematologist-oncologist at Children's Wisconsin, an authorized treatment center for Casgevy that will begin collecting cells from patients in 2025.

Apheresis can be dangerous for sickle cell patients because their blood can clot in the machine, causing a stroke. So patients first need to receive transfusions of donor blood to reduce their level of sickled cells. A single collection can take up to a week, and more than one may be needed to get enough cells to make Casgevy. Chow needed to endure four cell collections.

The cells are shipped to Vertex immediately to begin manufacturing. At that stage, a patient’s cells are edited with Crispr. Sickle cell disease arises from errors in a gene that makes hemoglobin, the substance that carries oxygen throughout the body and gives red blood cells their color. The edit used for Casgevy turns on the production of a healthy, alternative form of hemoglobin that the body naturally shuts off early on in life. Because the gene edit is permanent, researchers hope its effects will last for years or potentially even decades.

It can take up to six months from the time cells are collected to make Casgevy. Vertex must test the cells for purity and to make sure they contain the correct edit. (Off-target or unintended genetic edits are a possibility with Crispr). Vertex is ramping up manufacturing capacity for Casgevy in anticipation of growing demand. Once the cells are ready, they’re shipped back to the hospital.

Life on Hold

The next part of the process is what gives patients and families the most pause. Patients must undergo a high dose of chemotherapy in order to make space in the bone marrow for the edited stem cells. Chemotherapy can cause hair loss, mouth ulcers, fatigue, vomiting, and other unpleasant side effects.

“It’s a difficult treatment,” says David Jacobsohn, division chief of the blood and marrow transplantation program at Children’s National Hospital in Washington, DC. “It’s pretty intense, and patients can get quite sick.” Children tend to tolerate chemotherapy better than adults because their bodies are more resilient and their organs are healthier.

Beyond the short-term side effects, chemotherapy can result in infertility. For those who want to have children later on, it means freezing their eggs or sperm. But patients who haven’t yet reached puberty don’t have that option. (Casgevy is approved for ages 12 and older.) Vertex has said it will help patients with commercial insurance access fertility preservation services, but federal law bars it from doing the same for individuals on Medicaid because it’s seen as a financial incentive to use Casgevy.

Chow took the chance with his fertility. Now, he’ll remain in the hospital until early to mid-January while the stem cells migrate to his bone marrow and start making new, healthy red blood cells. Until then, patients’ immune systems are weakened, so they’re at particularly high risk of infection and other complications.

The amount of time spent going to doctors appointments and being hospitalized is a major consideration for patients who are in school or working. Doctors say many patients are interested in the therapy, but it’s a matter of timing it to when they don’t have other big life events going on. “Essentially, it’s a year of your life on hold,” Talano says.

For Chow, the end is in sight. “It’s been a long journey,” he says. He plans to spend the next several weeks composing rap music from his hospital bed to pass the time.

Jacobsohn is optimistic that demand for Casgevy will pick up over time, especially as patients hear about more success stories. “I think more patients will come, but until we figure out a way to do this with lower intensity chemotherapy, I don’t think it will be an option for every patient,” he says, “Right now it’s not at the stage where you can imagine every two- or three-year-old with sickle cell getting this. That would be an amazing place to get to in five or 10 years—a cure for everyone.”

Delivering a $2.2 Million Drug

Behind the scenes, hospitals have been navigating their own issues in order to begin offering Casgevy.

“Only now do centers have all the infrastructure to provide this in a slicker way,” says James LaBelle, associate professor of pediatrics at the University of Chicago, who specializes in cancer and blood diseases. The University of Chicago Medicine Comer Children’s Hospital was among the original nine locations in the US to offer Casgevy.

A hospital first needs to first complete an assessment to make sure it can perform the cell collections. It then signs an agreement with Vertex that covers the collection and shipping of patient cells for manufacturing, as well as receiving and storing Casgevy before it can be infused. This generally takes a number of months.

Hospitals are also dealing with insurance hiccups. Casgevy is a $2.2 million drug, which is just the cost of the medicine. That doesn’t include a patient’s many medical appointments leading up to receiving it, or their hospital stay afterward. Hospitals often purchase drugs first, then get reimbursed by a patient’s insurance after giving the drug. With Casgevy and other pricey drugs, this means hospitals take on a significant up-front cost. “There’s a big question of, how does the health care system absorb these very high-cost drugs?” LaBelle says.

Stephan Grupp, section chief of cellular therapy and transplant at the Children’s Hospital of Philadelphia, says doctors will likely need to secure a single case agreement from insurers on behalf of their patients. This is a contract to make sure that the insurer will not only cover the cost of the drug itself but also the medical services the patient needs during the whole process.

Insurers have started covering Casgevy, although Grupp says extensive paperwork and documentation is needed to show that a patient is eligible, and insurance authorization can take months.

Navigating state Medicaid programs is another challenge. Not all states have an authorized treatment center yet. Some Medicaid programs allow patients to go out-of-state for care, but there can be authorization delays. A new payment program led by the Centers for Medicare & Medicaid Services is aimed at improving access. The voluntary program means Vertex will be paid by states depending on whether the drugs improve outcomes for people who get Casgevy.

Despite Casgevy’s slow start, Stuart Arbuckle, executive vice president and chief operating officer at Vertex, told WIRED in an emailed statement, “We are delighted with the strong first year of commercialization.” (The company declined an interview for this story.)

Chow doesn’t know if Casgevy will eliminate his pain completely, but he hopes it will at least keep him out of the hospital. He now sees a future in which he could try out snowboarding—something he could never do before because cold temperatures can bring on pain crises. For now, he wants to continue making music and see his friends more. As for what’s next, “It’s all in God’s hands.”

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