Earlier this week, Tom Levenson linked to an excellent article by NPR on the promise of CRISPR technology for either long term symptom alleviation or cures for some people who have sickle cell anemia:
“I’m doing great,” Gray, now 36, said during a recent interview from her home in Forest, Miss. with NPR, which has had exclusive access to chronicle her experience for more than two years….doctors taking cells out of her bone marrow, and editing a gene in the cells in their lab, using the revolutionary gene-editing technique known as CRISPR….
The hope was the edited cells would produce a protein known as fetal hemoglobin, alleviating the symptoms of sickle cell…
And it appears to have worked, for Gray and other patients. Doctors have now treated at least 45 patients with sickle cell and a related condition known as beta thalassemia, and reported data indicating it’s working for at least 22 of them.
Sickle Cell Anemia is a genetic disease that is the result of two recessive genes expressing themselves so that red blood cells are bent instead of round. A single copy of the gene provides protection against malaria while both copies of the gene produce pain and lack of function.
Last week, the Duke Margolis Friday virtual lunch seminar had a speaker go over some of their new research on sickle cell. The TLDR from that talk is that sickle cell cures are a very nasty policy problem.
The first big thing is that the disease is very heavily racialized. African Americans are tremendously more likely to have the right combination of genes than people who identified as white.
Secondly, individuals with sickle cell are highly likely to be insured by Medicaid. Medicaid is a joint federal-state program. ACA Medicaid expansion has the federal government pay 90% of the costs and the states 10% while legacy Medicaid has the feds paying between 50% and 75% of the costs and states paying the remainder. The mostly former Confederacy states that have not (yet) expanded Medicaid under the ACA have a disproportionate share of individuals with sickle cell anemia.
Third CRISPR is expensive even in the context of US healthcare costs. A million dollar treatment cost is well within the realm of plausible and in some discussions that would be considered cheap. According to the NPR article, success is only happening in about half of the trial population. So there might be cases where a million dollars is spent for limited gains while other people can have massive improvements in quality and quantity of life for the same million dollars.
It is likely that a sickle cell cure will be cost effective under traditional health economics regimes. It is almost certain that a CRISPR based treatment will be a massive cash flow shock. Costs are incurred in the first period and the benefits are distributed to the individual over a twenty, thirty or forty year follow-on period. The Hep-C antivirals are a good analogy for a technological shock that is very cost-effective over a reasonable time horizon that is also a huge cost shock to the current payer period.
Several of my colleagues are thinking hard about how to structure contracts and payment arrangements that deal with massive expenditures with group level benefits but uncertainty and variance at the individual level. But no matter what, this is both very promising and one hell of a nasty policy problem.
oldster
Super interesting, and yes I can see how this could lead to really divisive social policy issues.
Is there any hope that technology will ride to the rescue by making the CRISPR techniques dirt cheap? It’s a new technology, so perhaps there is room for improvements, economies of scale, etc.?
Capri
As the grandmother of a child with cystic fibrosis, I’m monitoring all CRISPR advances closely. Like so much like this, I expect the costs to come down with time.
Aziz, light!
Thank you David for your very insightful post. It’s helpful to see the relation between a state’s political stance and health care outcomes.
WaterGirl
@Aziz, light!: Helpful, yes. Sad and enraging, also yes! :-)
Ken
This is surprising to me. Does this mean that a sickle cell patient will have over a million dollars in medical costs over their lifetime, so the treatment is cheaper? If that is the basis, then it would also seem to make sense to do the treatment in children, as early as possible.
Ramalama
@Capri: When I worked at MIT some research project costs budgeted hundreds of thousands of dollars for genomic sequencing. Funding was approved, projects started or continued.
And then, just like that, sequencing got orders of magnitudes cheaper and faster to do. The PIs all had to clamor to re-structure their research because they had ALLLL of this extra money leftover. They had to spend it or send it back. Obvs they added to their research, hiring more people or buying more supplies. But a bell was rung and EVERYONE had to hustle including the funding agencies, NIH & NSF. Probably everyone – DOE, NASA, big money private donors.
Also? I was commuting back and forth: Cambridge MA to Montreal for personal reasons – regularly. Scientists started adjusting their schedules to meet mine so that they could catch rides with me – keep working in Boston and visit their families (partners with children decided NO to Boston daycare nightmares). It seemed that everyone for the longest time was all working in imaging this, imaging that. Boston University, Harvard, Northeastern, MIT. People came down from McGill to learn techniques in Boston and take their know how back up North. I drove everybody.
All thanks to the breakthrough in sequencing, I think.
I hope that CRISPR revolutions also cause a similar cascade effect for your grandkid.
David Anderson
@Ken: Not quite… it means that the quality life of improvement is big enough and sustained enough that when we look at other things that we’re willing to get those same types of improvements, we’ve been willing to pay between $50,000 to $100,000 per full life year of full improvement… so if the improvement is big enough and sustained enough over enough years, a big number like a million dollars can be readily justifiable.
Blog post on this later this week as it is a good question.
Another Scott
Thanks for this.
I’m reminded of the story I posted recently of a woman who fell off her horse, was hospitalized, caught Covid in the hospital, ended up with a $1M bill and long Covid symptoms. (Can’t quickly find the link – it was in a Suzanne subthread talking about Covid and hospital acquired infections.)
We accept $1M “freak accident” cases. The numbers are likely substantially higher with sickle cell, but the issue is the same – we have a medical system where money flows to the top on the backs of those who cannot afford it. Dean Baker talks about this a lot. It doesn’t have to be this way, but we have to do the work to change it. Power doesn’t surrender willingly…
Thanks very much.
Cheers,
Scott.
MomSense
@Capri:
My grandparents lost two of their children to CF. The first thing I did the day I had genetic testing and found out I am not a carrier was to call my grandma. She broke down crying and she was the model of stoicism. I hope and pray that they can cure that disease.
Ella in New Mexico
Single payer. Single Payer. Single Payer.
Especially given people WON’T be using the same insurer or even Medicaid over the course of a lifetime, there is no incentive for health insurers not to bump this expensive treatment down the road in hopes their costs will be cheaper with any given patient and that some futuer insurer will eventually pick up the tab for CRISPR.
I see this every day in my work. Even with Medicaid providers or people purchasing off the exchange, it’s clear the thinking is “next year maybe they’ll switch to X insurance” is why–they can deny treatment on an expensive issue in hopes patients will suffer with it at least a year or more.
We cannot continue to to pretend that “good health care” is possible in a profit-based healthcare economy.
Hoosierspud
I first heard about CRISPR while listening to Radiolab. “The Code Breaker” by Walter Isaacson has a good explanation of it and also a fascinating look at how it was used to develop COVID vaccines.
Starfish
This price is stupid and unaffordable to the people that will benefit the most from this.
It is also stupid and unaffordable to the Medicaid systems of the states that will have the most of these cases (the Southern ones.)
Mousebumples
I’ve seen the changes in Hepatitis C drug coverage in my 3+ years working for a PBM, in terms of which patient situations are payable.
Obviously there is some variability, but overall it’s gone from “your liver disease isn’t severe enough for coverage” to “you meet FDA indication for use, so we’ll approve this”.
I’m not a party to the cost benefit decisions behind these changes, but it feels like an overall net benefit for the covered patient population. Don’t need to accrue all sorts of comorbidities before your viral infection can be treated.
Ohio Mom
Oh, just make it like dialysis (On my bad days, I am extremely jealous that there is this one medical condition that gets such favorable treatment while the rest of us live in constant, low-level fear that we or someone in our family will be wiped out by an illness. I guess this is a bad day.)
Another Scott
@Another Scott: Closing the loop – here’s the CaliforniaHealthline story I was talking about (posted on Friday).
Cheers,
Scott.
Starfish
@Ella in New Mexico: Even the non-profit insurance in a profit-based system are corrupted.
I am going to hold my breath for Southern states to put more into the state Medicaid system to cover a disease that primarily affects Black folks.
Pay no attention to how they acted during a pandemic when they thought COVID-19 primarily affected Black folks.
Should some aspects of medical care such as the ones that do CRISPR labs be seen as part of military readiness and be subsidized by some military budgets?
Yarrow
I haven’t read much about this except here. Do doctors know why it works for only about half of the patients? It’s great it’s working for so many but I feel for those who get their hopes up only to be in the “doesn’t work for me” group.
SP123
I work on this so can answer any technical questions y’all have. Can’t comment on the drug program itself.
Fair Economist
2 million dollars per success with sickle cell seems a slam dunk to me, at least for children. Roughly 30 extra years of life and a big improvement in quality for the 40-50 they’re already expected to have is worth 2 million. For beta thalassemia, no; there are decent treatments available for that. Of course costs are likely to drop. There really should be a way to alter the corrected cells to replace the existing cells with a technique less drastic than a bone marrow transplant.
David Fud
@SP123: I would guess my only real question (because I am not sufficiently savvy in this area) is related to questions already asked (if you know): do they have any idea why some (~50% of) folks are responding to the fetal hemoglobin treatment and the rest seem not to be? That is academically interesting in and of itself. We all know genetics and humans have weird and interesting quirks about expressing things and variability, and every time we get a chance to tease that apart, we seem to learn a lot.
way2blue
I’m wondering if this technique would also work for leukemia, since it too is due to mal-formed blood cells. Really promising…
Brit in Chicago
This sounds like great news!
On the political front, I was especially struck by this: “individuals with sickle cell are highly likely to be insured by Medicaid. Medicaid is a joint federal-state program. ACA Medicaid expansion has the federal government pay 90% of the costs and the states 10% while legacy Medicaid has the feds paying between 50% and 75% of the costs and states paying the remainder.”
I assume that the decision whether to cover the new treatment is a Medicaid (Federal) decision, not state-by-state (subject to correction by those who know more than I do). So if Medicaid covers it, the non-expansion states are faced with huge bills (at least for some time, until the price comes down). Won’t that put them under (yet more) immediate financial pressure to reverse course and accept Medicaid expansion? If so, win-win!
SP123
@David Fud: two possibilities.
Maybe too early to tell for the ones who haven’t responded yet- I don’t know how long it’s been since treatment of every patient but if you look up the data for patient 1 (VG in the NPR story) there’s a lag until the new cells take over and start making alternate hemoglobin.
Other is that the edited cells didn’t engraft and unedited cells regrew instead. That will definitely be reported by the end of the trial- the problem is it’s still ongoing so hard to definitively interpret interim results.
ETA: if there’s anyone who has edited cells but still doesn’t generate fetal globin that will certainly teach us something new about the disease!
cleek
just FYI, there are CRISPR alternatives out there.
my wife’s company, for example has their own tech: https://precisionbiosciences.com/arcus-genome-editing/
Ruckus
@Ken:
A very good friend of mine had sickle cell. As I stated the other day she would be in a hospital every time she had an attack, for several days. Over time those costs add up. Now I don’t know the actual costs of being regularly hospitalized but I’d bet that it ain’t cheap. I’d also bet that in a few of our states that monetary consideration might be used to deny treatment to persons of African decent, because as I stated in my comment the other day this happened in CA, so I’m guessing it would be very/highly more likely to happen in other states.
daveNYC
@oldster: I’m not sure if the CRISPR bit is the super expensive part of the treatment. The process involves harvesting the patent’s bone marrow, doing the genetweak, then nuking the patient’s existing marrow with chemo drugs so the tweaked stuff can be implanted and replace it.
WaterGirl
@Mousebumples:
PBM?
Ruckus
@Ella in New Mexico:
This is one of the best, most maddening comments ever. Not maddening that you made it, you said it perfectly, only that it is one of the absolute truisms of our healthcare system. As I’ve stated, I get my health care from the VA. I know people have discarded the concept but the healthcare is rather good, and doctors just order a procedure if it’s required, and it’s just done. Sure it could be better, what couldn’t, but my decades of insured, normal civilian life healthcare have shown me that any system that has to show a profit, especially one with high costs, is going to be inferior and have overall inferior outcomes because of that profit motive. Add racism into the cost control equation and that inferiority becomes far worse.
Victor Matheson
Super interesting. Of course, if this technology follows that of the hep drugs, that $1 million cost might come down 90% or so in the first decade or so. If the technology follows that of chromosome/gene sequencing that $1 million cost might come down 99.9% in the next decade.
Hallmark
Three questions for someone with knowledge of the payments side:
1 – Is $1M the all in cost? i.e. “drug” + hospital + ongoing therapy costs + whatever else. Does it include the cost of a caregiver not being able to work/keep a regular full time job for 6-9 months?
2 – How many days of ‘regular’ (not ICU level) will $1M buy? My wife treats patients with SCD. She has multiple patients that are in for 3-4 days, several times a year starting around age 10. Usually admitted via the Emergency Dept.
3 – What is the cost of a Bone Marrow Transplant? BMT is a curative treatment (if you can find a donor), but it ain’t cheap and there are real risks.
Mel
@Ella in New Mexico: This. You are so right.
As long as healthcare (and research funding, for that matter) remains a corporate controlled, for-profit structure in this country, human health and quality of life will never be the primary goal of our “health systems”. Antibiotic research is a prime example of how we fall short. We desperately need new and ongoing research to develop new drugs and new technologies to fight antibiotic resistant pathogens. But antibiotics are traditionally some of the lease profit intensive meds, so very little research funding is being directed at the problem, although it is an enormous and increasing threat to human life and to health systems all across the world.
The for-profit problem is made further complex and odious for anyone with serious or chronic health conditions by the opposing mindsets of the two entities that largely control access to healthcare and treatment here. Pharmaceutical companies want to fund research for and bring to market only those new treatments that will drive a large profit margin, and insurance companies in turn do not want to pay for expensive treatments.
Pharmaceutical companies try to offset the bad PR by going on about patient assistance programs, but the number of patients who actually qualify, or qualify for enough coverage / time to really make a difference is startlingly slim. So, for example, a person making 70,000 a year with private insurance would likely qualify for “help”, for many RA biologics, but only for the amount on the “copay assistance card” provided by the pharma company. “Look! we’re giving you $3,000 in assistance!” Sounds great, until you realize that your monthly copay is, say, $1,500. So, you only get to obtain 2 months of med, then your cost goes right back up to over $20,000 a year. Meanwhile, a disabled person on Medicare, who lives on $13,000 a year, is not eligible for any “help” from Big Pharma b/c they are supposedly “getting all the financial and insurance assistance they need from government programs.”
It’s heartbreaking and frustrating.
David brings up another important point that rarely sees the light of day in discussions about healthcare reform: the fact that research dollars and insurance coverage of treatments for rare diseases and/or diseases that are seen as diseases primarily affecting minorities are often given short-shrift.
I can speak personally to the grief, anger, and fear that come with knowing that there are treatments that could improve quality of life, perhaps even put a life-threatening illness into remission, and having them permanently out of reach.
SP123
@Hallmark: This treatment basically is a BMT but with your own cells that are modified to make non-sickling protein. So all the same steps are involved plus the process for collecting and editing the cells. But you lose the risk of not finding a donor since you are your own donor.
There are companies looking at doing the editing in vivo so no need for the full BMT process but that has another whole set of risks. If you edit ex vivo you don’t have to worry about accidentally editing other tissues that you don’t want to change. Making the same edit probably isn’t a big deal in this case but the huge fear is off target edits leading to cancer. Less risk of that editing the specific relevant cells outside the body.
taumaturgo
I agree with your statement. One realization that is beginning to dawn on people is that the duopoly of R & D is committed to protecting the financial abuse of big pharma and the profits before health insurers. There are NO significant changes that would improve the lives of people, on the contrary, the systems become more expensive while the outcome goes south, no matter which party is in charge. Is it less cumbersome when one party is “in charge” than the other? Barely. The gravy train continues to roll for the corrupt at the expense of the many and no amount of duopoly elections will reform the system. Look up, people.
Goku (aka Amerikan Baka)
@taumaturgo:
So, how does the fact that the Republican-controlled state legislature in Georgia is throwing black Democrats off local boards of elections and replacing them with white conservatives come into play with your “duopoly of R and D” BS framing? Or the other red states doing similar things?
Not saying there’s no corruption/inertia among some Dems wrt health care, but good god talk about being ultra-reductionist
taumaturgo
@Goku (aka Amerikan Baka):
Your attribution bias is telling, but understandable.
“There are NO significant changes that would improve the lives of people, on the contrary, the systems become more expensive while the outcome goes south, no matter which party is in charge.”
Mousebumples
@WaterGirl: pharmacy benefit manager – eg we’re the company that processes the drug claims at the pharmacy, review what your doctor sends in for Prior Authorization forms to see if you meet a drug’s criteria for approval, etc.
I probably shouldn’t name my company but it’s relatively small. (*compared to the big United Healthcare, etc. PBMs)
WaterGirl
@Mousebumples: thank you for expelaining what PBM means.
Goku (aka Amerikan Baka)
@taumaturgo:
Aside from the fact that you’re a condescending, patronizing ass, what the hell does that have to do with what I said?! Democrats aren’t antidemocratic and racist like the GOP are was my point. Republicans are deliberately trying to end democracy entirely and you’re telling me that “both sides” are the same? You sound like a fucking German Communist in 1933 talking about the Nazis and the SPD.
Mousebumples
@WaterGirl: no problem. To easy to get caught up in industry terms and forget not everyone just “knows” the acronyms!
JaneE
Couldn’t treatments like these be handled sort of like kidney failure is now? If you need dialysis, you go on Medicare immediately, regardless of age, because the cost is prohibitive and will be needed for the rest of your (probably not too long) life. This is the reverse case, where a massive up-front cost will accrue cost benefits for the rest of a (probably longer) life. It would take a new law, but couldn’t the federal government pay the one-time cost or at least the bulk of it? Too simple to work, probably, but it seems like the right place to send the bill.
Laura
A few years back I shared a hospital room with a woman with sickle cell. She was in intense and barely mitigated pain–unable to sleep more than 20 minutes at a time), but the (white, male) hospitalist wanted to discharge her home (she lived alone), despite her pain and the fact that she was incapable of getting out of bed or walking to the bathroom without aid. I listened to her repeatedly advocate for herself (it was very hard not to add my voice to hers) until the doc finally ‘gave in’ and allowed her one more day. Whatever amount of money we spend as a society to help people manage suffering and lead more productive lives is money well and appropriately spent. We could purchase fewer bombs or sell off a few military bases if we’re going broke to do so.
SP123
@JaneE: tangential point here but relevant for insurance coverage and a longer life- the prevalence of CF has actually gone up as treatments have been more successful. Some people cynically viewed this as pharma promoting diagnosis of more patients so they could make more money. In reality it’s because CF is no longer fatal by age 30 so the total number of people living with the disease has gone up because they don’t die. I think something similar happened with HIV at one point, and I expect it would happen with SCD if successful treatments become widespread
taumaturgo
@Goku (aka Amerikan Baka): Both sides are the same when it comes to passing legislation that would significantly improve the delivery of healthcare. Both parties accept legal bribes from big pharma and insurers to make sure they retain the right to rip off you and me, social issues notwithstanding.
Goku (aka Amerikan Baka)
@taumaturgo:
Imagine reducing basic support for representative democracy and and voting rights to “social issues”, as if they’re unimportan
You’re a moronic unserious person
texasdoc
@daveNYC: This is true, and most of the complications of the procedure and much of the cost relate to the expense of the myeloablative (nuking the bone marrow) part, including the hospital stay while you wait for the new cells to engraft.
taumaturgo
@Goku (aka Amerikan Baka): If we had a representative democracy I would support it, but all the empirical evidence suggests we don’t. Our representatives don’t work for us, witness the disastrous delivery of basic social needs such as housing, education, and healthcare. If you still cling to that notion and hominem attacks are your last resort, go after the de facto president and corrupt in chief Manchin. Sinema if you prefer an easier target.
burnspbesq
@Starfish:
So what are you suggesting? The stuff costs what it costs. Focus on who pays, and why. Otherwise your rage is unhelpful.
Starboard Tack
@taumaturgo: My representative does work for her constituents within the limits of what’s possible. Maybe she could do more if she’d keep her ring recharged.
taumaturgo
@Starboard Tack: Impossible. I don’t who your representative is but for sure she was elected within the current rules of the game which dictate that she spends an inordinate amount of time groveling for money from the same corporate power that would dictate which way she’ll vote. Only a handful of representatives have renounced accepting corporate money if she is one of the congrats.
Starboard Tack
@taumaturgo: She generally supports the same things I do. Sounds like you should find a lot of small donors and be a candidate for something. Or is it all you can do to bitch?
taumaturgo
@Starboard Tack: Sorry. You must be part of the 1% or an unembarrassed plutocrat wannabe who supports them from the Manchin wing of the party?
Starboard Tack
@taumaturgo: Neither. And I’m not affiliated with a political party. I generally read all the comments on here and, while I’ve never done this before, it’s pie for you.
randy khan
@Ken: @David Anderson:
I had the same question. The current best drug (which reduces sickle cell incidents by about half) costs something like $85K per year, and I found a 2009 study (which is to say it’s now way out of date) that estimated lifetime additional healthcare costs for sickle cell patient of around $450,000.
Conveniently for the math (but not so for the patients), since indications are that the CRISPR approach will cure about half the patients, your average crossover between the two types of treatment would be between 11 and 12 years, so it would save a ton of money compared to current treatment options if you could use the CRISPR treatment early in someone’s life. And I assume that the present value of the costs of care have gone way up since 2009, making the million dollars look not so bad.
In a universe where you could just give the CRISPR treatment to people as they’re diagnosed, it’s probably a big net cost savings as compared to current treatments, but as Mr. Anderson says, that first couple of years are a big bump up in cost.
Doug
Reparations.
Starfish
@burnspbesq:
If the state has to pick up any of the cost, states like Mississippi will absolutely harm the Black folks who live there by not covering it. Federal government needs to pick up 100% of the cost.
A lot of costs associated with CRISPR are lab costs. A lot of rural hospitals try to attract doctors by helping pay off student loans as part of their pay package. Could a benefit like this be used to contain costs in some way? I am not sure how this would work.