"A functional (but expensive) cure".

December 8, 2023 11:58 AM

The U.S. Food and Drug Administration has approved two new gene therapies treating sickle-cell anemia, called Casgevy and Lyfgenia.

While Lyfgenia relies on a lentiviral vector for genetic modification, Casgevy is the first FDA-approved treatment to rely on CRISPR gene-editing technology, a major milestone in the field of gene therapy.

In both cases, "The patient is their own donor": "the products are made from the patients’ own blood stem cells, which are modified, and are given back as a one-time, single-dose infusion as part of a hematopoietic (blood) stem cell transplant."

"Sickle cell anemia is caused by a change in the gene that tells the body to make the iron-rich compound in red blood cells called hemoglobin. Hemoglobin enables red blood cells to carry oxygen from the lungs throughout the body. The hemoglobin associated with sickle cell anemia causes red blood cells to become rigid, sticky and misshapen." It is an inherited condition affecting approximately 4.4 million people globally, overwhelmingly of sub-Saharan African descent. A 2013 study "found that the average life expectancy for women with SCA was 42 years and 38 years for men."

"Still, the new therapy is extremely expensive - $2.2 million per patient, Vertex said. The pricing strategy, experts argue, may place it out of reach for many families. What’s more, that price doesn’t include the cost of care associated with the treatment, like a stay in the hospital or chemotherapy. We really have to make sure that it is accessible,” said Dr. Rabi Hanna, a pediatric hematologist-oncologist at the Cleveland Clinic who has previously served on the advisory board for Vertex."

posted by mhoye (13 comments total)

If I'm reading this right, this isn't a treatment, it's a cure, one that basically doubles life expectancy. A couple million dollars seems cheap in that context and should be covered for the public good, either by insurance or the government. Of course we have the shittiest healthcare arrangement possible, so...
posted by rikschell at 1:13 PM on December 8, 2023 [22 favorites]

Indeed rikshell!

According to this article, the lifetime burden of medical costs attributable to SCD over a lifetime is around $1.7 million.

Considering this is a brand new treatment, it's also likely to become significantly cheaper and I suspect that the $2.2 million is already cheaper than the full costs over someone's lifetime when you also factor in quality of life, lost wages due to illness and lost opportunities.
posted by ursus_comiter at 1:43 PM on December 8, 2023 [6 favorites]

Am I remembering right that SCD disproportionately affects people with sub-Saharan ancestry? If so, in addition to being a stunning scientific achievement generally, this would seem to be a big win for health equity, too.
posted by eirias at 1:57 PM on December 8, 2023 [5 favorites]

NPR has done a series of interviews over the past few years with Victoria Gray, the first patient to be treated with what I guess we're now calling Casgevy.

July 2019
Dec 2019
June 2020
Dec 2021
Mar 2023
Dec 2023

As a biology professor who both uses sickle cell as an example in class (the genetics and evolutionary history along with malaria are fascinating) and who has known many people with sickle cell disease and trait, I've cried along with Victoria Gray during these stories so many times!
posted by hydropsyche at 2:00 PM on December 8, 2023 [7 favorites]

Yes, sickle cell is commonly found in Sub-Saharan African populations, as well as some Southern Europeans and South Asians--places with malaria. Here is a decent article about that, but in short, having two alleles for the sickle cell gene gives you sickle cell disease which yields a short painful life. Having only one allele gives you sickle cell trait, which has very few effects on the body except for making you resistant to malaria. Thus, in places where malaria is common, sickle cell persists in the population through heterozygote advantage.
posted by hydropsyche at 2:05 PM on December 8, 2023 [8 favorites]

Completely agree this is fantastic news!

Re the cost, the patient population for sickle cell in the USA trends towards those on Medicaid and those in the lower income groups with the usual (lousy and variable) employer-provided insurance, so in some ways similar to those with other diseases treatable with gene-based therapies but also different in their historical undertreatment by the medical community. I expect coverage for this therapy will be handled similarly to other gene therapies, meaning poorly based on how insurance has handled SMA (which at one point (and may still) offer care based on a lottery in some cases to see who gets care) and CF (which a PR effort recently tried to declare cured despite a number of issues including accessiblity and mutations which are not treatable under the major therapy) and other conditions which saw huge jumps in cost as treatment went from research to clinical standard. I've seen articles in Nature stating it would be 20 billion USD to cover everyone today and of course would grow as more diseases become amenable. My hope is that the technology behind these will become so generalizable that arguments about industry needing to recoup expenses fall cannot be actually supported.
posted by beaning at 2:22 PM on December 8, 2023 [2 favorites]

I am curious what the actual cost is for this on a per treatment basis.

I can’t quite grok the idea that because it doubles lifespan it should cost millions of dollars. The five dollars of penicillin I took for a bad abscess when I was 14 also probably saved my life, or at least my jaw. Should they have charged a million dollars for that too?
posted by rockindata at 3:25 PM on December 8, 2023 [2 favorites]

This is good and exciting, and anyone who has ever cared for a patient with sickle cell disease and its complications is generally cheering right now. It's a miserable disease, with high morbidity and mortality, and there is so much stigma for people who have it.

An ASH publication estimated lifetime cost of care for SCD at $1.2M on average. But people with SCD have shortened lifespans, and if this is a treatment that helps these patients live normal, non-hospitalized lives, if it lowers the need for opioid pain control (and hence the risk of accidental overdose) ... worth it to me. The drug companies will eventually realize that if they want these therapies to be used, the costs will have to catch up to what payors will pay.
posted by honeybee413 at 3:39 PM on December 8, 2023 [1 favorite]

Rockindata, pricing models vary but most are some combination of "cost = recoup of research + medical costs that are included as a "benefit" since the pt will now not have to pay someone else (reduced lifetime costs of other drugs, hospitalizations, etc) + general admin/overhead + an increased quality of life benefit ". So your abscess treatment likely is not "research-based" nor does it avoid other treatments and treatment per se does not substantially change your quality of life.
posted by beaning at 3:40 PM on December 8, 2023

So your abscess treatment likely is not "research-based" nor does it avoid other treatments and treatment per se does not substantially change your quality of life.

I would have thought the big difference would be that there's no patent-enforced monopoly on penicillin. Those calculations really just set a ceiling, if there's loads of companies competing on price, the price will be a lot lower.

If there's not much in the way of competition then the price will bump up to against these sorts of calculations. The "competition" for cures are (expensive) lifetime treatments; the cures can be competitive just by being a bit less expensive than a lifetime of treatment.

I did read that when the new Hepatitis C cure came out it was threatening to blow a huge hole in budgets because, even though it's competitive when measured against a lifetime of treatment, moving all those costs from "across several decades in the future" to "right now" is, uh, tricky.
posted by BungaDunga at 5:03 PM on December 8, 2023 [2 favorites]

Good news, but man, the treatment plan sounds rough:

While technically a one-time treatment, a number of steps that span months are required before the patient actually gets the modified stem cells. It begins with a series of blood transfusions over three to four months, after which the stem cells are extracted from the patient’s bone marrow and sent off to a lab where they are edited, Hanna said.

Before they can be reinfused into the patient, however, doctors need to make sure no flawed stem cells remain in the body. To do so, chemotherapy is used to destroy the patient’s bone marrow.

(emphasis mine)
posted by pwnguin at 9:36 PM on December 8, 2023 [4 favorites]

As hydropsyche notes sickle cell is the classic case of a disease which appears to be maintained in some populations because 'carriers' have significant immunity to malaria (which is no fun) because the different β-globin makes the red blood cells uncomfortable for the malaria parasites so they do not propagate there. See also Thalasaemia where a change in an α-globin gene provides similar protection in 'Mediterranean' populations. That condition is presumably in the sights of MegaPharm.

My quick read says that, in this new treatment, both copies of the β-globin are flipped to normal, so the r.b.cs. maintain normal shape and no disease. Do I take it that these folks are now fully susceptible to malaria? We have treatments for malaria, so that seems like A Good Thing on balance. When CRISPR therapy is rolled out to cure other conditions there may be careful what you wish for consequences.

For example the Δ32 mutation in the CCR5 gene provides natural immunity to HIV-1 but increased susceptibility to West Nile Virus.
posted by BobTheScientist at 12:43 AM on December 9, 2023 [2 favorites]

pwnguin, yes, this is essentially a bone marrow transplant, a type of therapy used for certain kinds of cancers for many years. That first phase, where the patient's existing marrow is destroyed, is indeed brutal.

Traditionally, cancer patients have had their own marrow replaced with someone else's, ideally a close relative, so that their body's immune system won't react too harshly against it. But people still often have to take immunosuppressant drugs to be able to tolerate the new marrow. My dad was lined up for this therapy when he had multiple myeloma, but unfortunately was judged too sick to undergo the first phase of it, and ultimately succumbed to the cancer.

In recent years, there's been encouraging progress in immunotherapies like this sickle cell treatment that involve self-transplantation, where some of the patient's own marrow cells are extracted, genetically altered, cultivated, then reintroduced after the rest of the marrow is killed off.
posted by Artifice_Eternity at 10:57 AM on December 9, 2023 [1 favorite]