The FDA has just approved two drugs that could change for the better millions of lives.
Both address sickle cell anemia. Casgevy is the first CRISPR-Cas based drug to get the nod for its gene editing approach to enabling a sickle cell patient’s body to produce the type of hemoglobin needed to carry oxygen through the bloodstream, while the other therapy, Lyfgenia uses a different approach.
Casgevy, which was called exa-cel in clinical trials, works by editing a patient’s bone marrow stem cells to make high levels of fetal hemoglobin — the healthy, oxygen-carrying form of hemoglobin produced during fetal development that is replaced by adult hemoglobin soon after birth.
Unlike adult hemoglobin, fetal hemoglobin resists forming a crescent shape in sickle cell patients, and scientists have long searched for a way to restart it. The researchers behind Casgevy solved the problem by editing a gene called BCL11A, which regulates fetal hemoglobin.
Crucially, these offer something approaching a cure for the disease. A clinical trial of Casgevy saw 29 out of 30 patients eliminated sickle cell flares for at least a year after treatment. Lyfgenia has seen similarly promising results.
The catch: both treatments are difficult and not tolerated by everyone who might benefit:
Casgevy and Lyfgenia requires several months of preparation, including a grueling regimen of chemotherapy to make room in patients’ blood marrow for genetically edited or modified stem cells.
The treatment involves multiple steps over several months. Patients must donate stem cells to be modified at a laboratory. Then the patients undergo chemotherapy. Finally, they get the cells back through a single infusion.
One consequence of the complexity involved is that, at least for now, not that many people will get the treatment. There are only a handful of medical centers able to deliver Casgevy right now, and they can handle roughly ten patients per year each–not a huge bite out of the ~800,000 or so sickle cell patients in the US, much less the roughly eight million world wide. And, of course, both drugs, though still unpriced, are going to be costly as hell:
Although both treatments are expected to cost at least $1 million per patient, advocates for makers of gene-based drugs said people need to compare such transformative medicines to major medical procedures — not to ordinary drugs.
That is, a one time treatment for a chronic and/or ultimately fatal condition can have a huge upfront cost and still be worth it–the example given in the Globe article is the cost of a heart transplant, also well over million bucks. There’s a lot more to be said about this, and David Anderson is the one to say it.
There is of course one elephant in the room. This first gene-editing therapy targets a debilitating and sometimes killing disease that hits mostly Black Americans. The argument over whether private insurance and/or Federal health care coverage should be required to pay for these therapies will be…interesting.
But all those caveats–complexity, cost, equity–aside, this is still an amazing result. It’s not quite like the inflection point when the prospect of vaccinating against infectious disease utterly altered the balance between humans and microbes/viruses. But it’s the same kind of conceptual change. We live in way-too-interesting times, but not all the news is bad.
To put it differently: Science, peeps!
Open thread.