Originally published on
By Meg Tirrell, CNN
The US Food and Drug Administration on Friday approved two gene-based treatments for sickle cell disease, including the first therapy that uses the gene-editing technique CRISPR, opening a new era of treatments for genetic Whether people will be able to afford and access these treatments, though, is a key question. One-time genetic treatments typically carry price tags of upwards of $1 million each and require the infrastructure of large medical systems.
“I don’t know whether it will get covered and paid for,” Hsu said. And the types of academic medical centers that could offer the treatment are typically in larger cities, he noted.
“I’m in Illinois, and they’re basically concentrated in Chicago, which leaves the entire rest of the state kind of bare, and so people would have to travel a very long distance to be able to get to this,” he said. “And then some states, there just isn’t anything.”
And the treatment isn’t simple; it requires a lot of additional care around it that adds to the cost. Patients typically stay in the hospital for about a month to prepare for the re-infusion of gene-edited cells, first going through what’s known as “conditioning”: several days of chemotherapy to wipe out their bone marrow, which makes blood cells and platelets, so they’re ready to receive the new cells.
Then, “it takes a period of time for those cells to kind of take up residence in the bone marrow and grow,” Bhatia said.
That period around the infusion can be very difficult for patients and their families; Johnny’s mom described how Johnny’s “whole GI tract was inflamed; he couldn’t swallow. That was really painful. It was hard to watch.”
And that chemotherapy conditioning carries risks, including the possibility of infertility, Hsu noted. He pointed out there are methods of trying to preserve fertility before the treatment, but coverage for that can vary by state as well. And more than half of people with sickle cell in the US depend on Medicaid for their primary insurance, according to the advocacy organization Sick Cells.
The conditioning treatment also carries a potential risk of cancer; two patients in earlier stages of bluebird’s trial died after developing leukemia, which was found unlikely to be related to the gene therapy itself but potentially from the chemotherapy needed to prepare for it.
Vertex’s Altshuler said his company is working on improving the conditioning process to make it gentler, to “create the opportunity for the new cells to go in without any other damage to the body,” although he noted that it’s still in the research phase.
Scientists also are vigilant about potential off-target effects of the CRISPR gene-editing approach – meaning DNA could be cut in an unintended place – and the FDA convened a full-day meeting in October to assess those risks. Many experts there expressed confidence that those risks were “relatively small.”
To Altshuler, the bigger deal in an approval of Casgevy is that there’s such an advancement for sickle cell disease, not that it’s the first CRISPR therapy.
“We’re not about a tool; we’re about the disease,” Altshuler said. “Once we found the way in, and now we’ve shown you can treat this disease very effectively if you can increase fetal [hemoglobin], we’re going to drive on that.”
The company is in the very early stages of researching how to achieve an increase in fetal hemoglobin using a pill, so patients wouldn’t need to go through the conditioning and gene editing process, Altshuler said.
He noted that it’s very early days but said that kind of approach could be the answer to the “very valid” question of “how are we going to help people around the world with this therapy?”
The majority of patients with sickle cell live in Africa and India, and bluebird’s Obenshain said the company doesn’t have plans to introduce “this version” of its gene therapy there, noting that it’s too expensive to manufacture.
“Basically, for every patient, we manufacture one drug lot,” Obenshain said.
For Johnny and his family, the effects of his treatment have been so transformative they now celebrate the day he got the infusion of gene-edited cells as his second birthday. He can go swimming – previously an activity guaranteed to trigger a pain crisis – without fear and spent all of last summer in the pool, his family says.
And although he didn’t gain the superpowers he worried about, he got something potentially even better: the chance to be a normal kid.
“I’m starting to teach him how to drive,” said Johnny’s dad, JR Lubin. “So we’re stepping into the regular worry of, you know, raising a teenager.”
The medicines, called Casgevy and Lyfgenia, are potential cures for people with sickle cell, a debilitating and life-shortening inherited red blood cell disorder that disproportionately affects African Americans.
Casgevy is the CRISPR-based treatment, made by Vertex Pharmaceuticals and Crispr Therapeutics, while Lyfgenia, made by Bluebird Bio, uses an older gene therapy approach. Both were cleared for people age 12 and older with histories of vaso-occlusive crises, painful events caused by the disease.
“Sickle cell disease is a rare, debilitating and life-threatening blood disorder with significant unmet need,” said Dr. Nicole Verdun, director of the FDA’s Office of Therapeutic Products within its Center for Biologics Evaluation and Research. “We are excited to advance the field especially for individuals whose lives have been severely disrupted by the disease by approving two cell-based gene therapies today.”
Johnny Lubin is one of the youngest people to have had the CRISPR treatment, as part of a clinical trial. Before he went through it, he recalls, he had one main concern.
“I was worrying that I might get, like, superpowers,” said Johnny, now 15, who lives in Trumbull, Connecticut, about 60 miles north of New York City.
For many in the sickle cell community, the approvals have been a long time coming. The disease afflicts about 100,000 people in the US, including an estimated 1 of every 365 Black babies born, according to the US Centers for Disease Control and Prevention, and has long been considered neglected by the pharmaceutical industry. About 20,000 people in the US are thought to have a severe enough form of the disease to potentially qualify for a treatment like this.
“To have sickle cell suddenly be the focus of this dramatic new approach to therapy development is, on the one hand, great, because hopefully it will undo some of that history of neglect and really give the sickle cell community the attention that is always needed,” said Mayo Clinic bioethicist Megan Allyse. She notes, however, that access to such a cutting-edge treatment remains a major question.
https://pubads.g.doubleclick.net/gampad/ads?iu=/138871148,22542901369/stlargusnews.com.dv.preroll&description_url=https%3A%2F%2Fstlargusnews.com%2F&tfcd=0&npa=0&sz=640×480&gdfp_req=1&unviewed_position_start=1&output=vast&env=vp&impl=s&correlator=&plcmt=2&vpmute=1