Casgevy

Summary

Second half of the CRISPR page: what happens after approval. Casgevy costs £1,651,000 at list price in the United Kingdom, with a discount to the public health service whose size is declared commercially confidential, and US$ 2.2 million in the United States — above the ceiling of US$ 1.35 to 2.05 million that the independent assessor had calculated before approval. But what limits access is something else: NICE counts 1,794 eligible people in England and projects 23 completed treatments in the first year, and the reason it records is the long hospital stay. A 2026 cost-effectiveness analysis showed that haploidentical transplant beats gene therapy in 10,000 of 10,000 simulations. 515,000 babies are born per year with sickle cell disease, mostly in sub-Saharan Africa and the Caribbean, and the estimated cost-effective ceiling in Nigeria is US$ 4,200 — 520 times less than the price. In Brazil there is no registration, no petition and no clinical trial.

What this page answers

The CRISPR page shows that the technology worked: the edit took in 100% of patients in the two phase 3 trials, and 97% became free of vaso-occlusive crises. This page begins where that one stops. Working and arriving are different things, and the distance between the two is the subject here.

The short result, and it is not what one expects: the declared bottleneck is not the price. When the British assessor explains why it projects low uptake, it does not cite cost. It cites the hospital stay.

The price, in the two currencies in which it is public

The British price is stated in identical text in NICE's two guidances — the beta-thalassemia one, published on September 11, 2024, and the sickle cell disease one, published on February 26, 2025.

The price was set above the ceiling the independent assessor calculated

Before FDA approval and before any announced price, the American health technology assessment institute published a reference range for exa-cel and for its competitor: US$ 1.35 to 2.05 million. It is the range the institute describes as the highest price a manufacturer should charge before the cost starts to cause disproportionate health loss in other patients of the same system.

The price came out at US$ 2.2 million — above the top of that range.

The caveat matters: the range was calculated before the price existed. It is a comparison of a prior estimate with a later number, not a judgment by the institute on the final price.

The eligibility funnel, with every percentage exposed

NICE publishes the whole calculation. It is worth following step by step, because this is where “approved for sickle cell disease” becomes 78 people per year.

And from eligible to treated

The following table is from the same report. The last line is the one that matters.

The reason NICE gives, and that nobody repeats

• It does not cite price. The recorded justification for the low uptake is that “a long hospital stay is required for the process involved”. The product is paid for, approved and available — and still it is 23 people in the first year, out of 1,794 eligible.
• In beta-thalassemia the picture is the same, on a smaller scale. There are 475 eligible in current practice, reaching 498 in 2028-29, with projected market share of 3% in the first year rising to 11% in five years: 14 people treated in the first year, 10 per year afterwards.
• Note the donor filter. The authorization requires that transplant be appropriate and that there be no matched related donor. Casgevy is not an alternative to transplant: it is what is offered to those who were already candidates and found no donor. The indication was designed inside the niche that transplant left empty — and that matters again two sections ahead.

United Kingdom: “managed access” is a polite way of saying it is not yet known

In both indications, NICE did not recommend routine use in the NHS. It recommended with managed access — a provisional data collection regime while the uncertainty remains unresolved. The expression it uses for the cost-effectiveness estimates is “highly uncertain”.

In beta-thalassemia the wording is direct: some of the most likely estimates are above what NICE normally considers an acceptable use of NHS resources, even taking into account the impact on health inequalities. Hence, not recommended for routine use.

In sickle cell disease, NICE explicitly accepted more uncertainty and a higher cost-effectiveness estimate than it would normally accept, and names the three reasons: the health inequalities faced by people with the disease, the innovative nature of the technology, and benefits not captured in carers' quality of life.

In cold terms: the NHS paid an equity premium and wrote it down. It acknowledged that the population with sickle cell disease is systematically underserved and adjusted the threshold because of it. It is a defensible and explicit decision — and it is also the formal acknowledgment that, on the purely economic criterion, the product did not pass.

The uncertainties it lists in the two guidances are fundamental, not detail: model structure, survival and quality-of-life outcomes, how long the treatment effect lasts, how often people drop out before infusion, and the frequency of complications.

United States: a federal model designed for this problem

Sickle cell disease, in the United States, is disproportionately a disease of the population covered by Medicaid — public insurance, state budget. A price of US$ 2.2 million lands on budgets that have no way to absorb it.

The answer was to create a model in which the federal government itself negotiates outcome-based agreements with manufacturers, on behalf of the states: participating states receive guaranteed discounts and rebates if the therapy does not deliver the promised benefit.

In an announcement of July 15, 2025: 33 states, plus the District of Columbia and Puerto Rico, joined. The federal agency states that 84% of Medicaid beneficiaries with sickle cell disease live in participating states.

But there is the arithmetic, and it is hard. Analysis from the perspective of Colorado Medicaid, with real data from 2018 to 2023:

What this arithmetic means

• Within the horizon of a payer contract, the therapy does not pay for itself. The standard of care costs about US$ 46 thousand per year; the therapy costs the equivalent of 48 years of that standard, paid up front all at once.
• And whoever pays up front is not necessarily who reaps the benefit. Any “saves money in the long run” argument has to cross that cash gap — and, in the United States, patients switch plans. The payer that funds the cure may not be the one that stops paying for the avoided hospitalizations.

The comparator the discussion avoided

This is the hardest piece of the survey, and it is from 2026. A cost-effectiveness analysis published in Blood compared three strategies in adults and children with sickle cell disease: standard of care, haploidentical allogeneic transplant with non-myeloablative conditioning — the one in which the donor is half-matched, a father, a mother, a sibling — and gene therapy.

Three readings, with the care the data demands

• Gene therapy wins on quality-adjusted life years — 22.1 against 20.1. Haploidentical transplant is not clinically better. It is cheap enough to win the economic comparison by an overwhelming margin.
• And it attacks precisely the niche of the indication. Casgevy is approved for those who have no HLA-matched related donor — and the haploidentical transplant is exactly the technique that dispenses with full matching. If it matures as a routine option, Casgevy's indication shrinks from within.
• US$ 4,200 in Nigeria. The American list price is 520 times that ceiling. It is not a matter of negotiating a discount: it is a difference of orders of magnitude that no commercial agreement closes.

Where the patients are, and where the therapy is

Global Burden of Disease Study, 204 countries and territories, 2000 to 2021 series.

The two halves, side by side

• 515,000 births per year, mostly in sub-Saharan Africa and the Caribbean.
• 78 people per year treated in England, in the peak scenario projected by NICE.
• Estimated cost-effective ceiling in Nigeria: US$ 4,200. List price: US$ 2.2 million.
• Sickle cell disease is, by evolutionary origin, a disease of populations from regions with endemic malaria. The world's first CRISPR therapy was approved for it — and the price was set at a level that excludes, by construction, the countries where the overwhelming majority of patients are born. It is not a market accident: it is the predictable result of the development model.

There is a technical proposal to change this

A multidisciplinary task force published in Nature, in 2024, a roadmap for affordable genetic medicines. The central proposal is a pricing structure that, according to the authors, could cut the cost per patient tenfold, combined with a business model that distributes responsibilities among diverse funding sources, academic licensing provisions, manufacturing innovation and supportive regulation.

The underlying argument is factual and verifiable: every approved cell and gene therapy was born in academic or government institutions. The dependence on for-profit companies for later development is what produces prices calibrated to recover investment, pay for the candidates that failed and meet shareholder expectations — and it is this, not manufacturing cost, that the authors identify as the origin of the category's price level.

The price that is not charged in money

It is detailed on the CRISPR page, but it needs to be recalled here, because it is part of the cost of access and appears in no price table.

Busulfan conditioning is gonadotoxic. In a single-center experience with 40 patients undergoing gene therapy, the 17 women with more than a year of follow-up all presented ovarian failure, with undetectable anti-Müllerian hormone.

This means that real access to Casgevy presupposes prior access to a fertility preservation service — one more procedure, more cost, more time, and one more specialized service that needs to exist in the patient's city. That is access too.

In Brazil: not a slow queue, a queue not started

Query on September 4, 2026 of the public petition database — the “Situação de Documentos” system, which allows filtering by CNPJ and by subject code.

Gene and cell therapy does not enter the drug register: it is an Advanced Therapy Product, with separate registration under RDC 505 of 2021. Searching for “exagamglogene” in the open drug database returns zero, and that means nothing — it is the wrong database.

The complete universe of advanced therapy registration applications ever filed at the Agency, adding up the four subject codes that exist for that, is 12 petitions, from 9 companies. These are the 11 of Class II:

The sweep that closes the question

None of the 12 is from Vertex, holder of Casgevy. To rule out the hypothesis of the petition sitting under another subject code, the sweep was redone by CNPJ.

Vertex Farmacêutica do Brasil — identified by the CNPJ listed as holder of the registrations for Trikafta, Symdeko, Orkambi and Kalydeco, all cystic fibrosis drugs — has 541 petitions in the system. All were downloaded and classified by subject.

What this means for the SUS

• There is no registration application for Casgevy in Brazil, and there is not even a clinical trial application. It is not a case of “it is in the queue and takes time”: it never entered the queue.
• The Portuguese-language sources claiming approval “in early 2024” are wrong. This can now be stated on positive evidence, not on absence of proof.
• Without registration, the incorporation committee cannot even evaluate it. Decree 7,646/2011, in article 15, requires that the application for incorporation into the SUS support the process with the number and validity of the registration, in addition to scientific evidence, comparative economic evaluation and the price set by the regulation chamber. The Brazilian debate on Casgevy's price is not stuck on price — it is stuck three steps earlier.
• What was not verified: whether any petition was filed by another legal entity on behalf of the product. The query is by CNPJ and by subject code, and the public interface does not return trade names. A text search for “exagamglogene” would require the SEI Public Search, which asks for a CAPTCHA and was not used.

And, if it ever unlocks, we will assess in the dark

CONITEC's Recommendation Report No. 924, from 2024, which establishes the clinical protocol for sickle cell disease in the SUS, carries the official Brazilian epidemiology — and the hole inside it.

The denominator that does not exist

• In 2024, the best official estimate available is from 2007, and it varies by a factor of two. The country has had universal newborn screening with 84% coverage for more than a decade and cannot say the size of its own patient population.
• Practical consequence: if and when Casgevy reaches the incorporation committee's table, the budget impact assessment will be done on a denominator from 17 years ago, with 100% uncertainty.
• Compare with the United Kingdom. There it was possible to publish 1,794 eligible people with the whole funnel exposed — genotype, number of crises, fitness for the procedure, absence of a donor — because it is known who they are. The access gap, here, begins as a data gap.

Real adoption — the weakest section of this page

⚠️ I found no independent public record of how many patients have received Casgevy worldwide. What exists is the manufacturer's statement and the trade press that reproduces it. The company's investor page returned an access error in the attempts made for this survey. Nothing in this section was checked against a primary source.

According to trade press citing the manufacturer, by June 30, 2025: 115 patients had their first cell collection and 29 were infused, 16 of those infusions in the second quarter. Reported Casgevy revenue in 2025 was US$ 115.8 million.

If the revenue and the list price are both correct, the division gives about 53 treatments — the same order of magnitude as the 29 infused by mid-year, and consistent with what NICE independently projected for England. It is a consistency check, not confirmation.

What can be said without depending on those numbers: the distance between 115 collections and 29 infusions, if real, is of the same nature as the 81% completion NICE projects. Entering the process and finishing it are different things, and the difference is measured in months of hospital.

What this survey shows

• The declared bottleneck is not the price — it is the hospital bed. When NICE explains why it projects low uptake, it cites the long hospital stay, not the cost. A rich country, with the product paid for and available, treats 23 people in the first year out of 1,794 eligible.
• The price was set above the ceiling the independent assessor calculated. US$ 1.35 to 2.05 million was the range; US$ 2.2 million was the price.
• Within the horizon of a payer contract, the therapy does not pay for itself. Standard of care at US$ 45,941 per year; cumulative balance of −US$ 2.11 million per patient over 6 years.
• There is a cheaper comparator that wins in 10,000 of 10,000 simulations — and that attacks precisely the niche of the indication, because it dispenses with the full HLA matching that defines that niche.
• The NHS paid an equity premium and said so in writing. It accepted greater uncertainty and worse cost-effectiveness than it normally accepts, because of the health inequalities affecting people with sickle cell disease. That is honest — and it is the acknowledgment that, on the purely economic criterion, the product did not pass.
• The distance between where the patients are and where the therapy is spans orders of magnitude. 515,000 births per year against 78 projected annual treatments in England; a cost-effective ceiling of US$ 4,200 in Nigeria against a price of US$ 2.2 million.
• And there is a human cost that no price table shows: 17 of 17 women with more than a year of follow-up had ovarian failure.
• In Brazil, the queue has not even started — 541 petitions from Vertex, zero for advanced therapy — and the denominator does not exist: the best official estimate of how many patients there are in the country is from 2007 and ranges between 25 thousand and 50 thousand.

References

1. NICE — guidance TA1044, exagamglogene autotemcel for severe sickle cell disease in people 12 years and over, published on February 26, 2025. Section 2 carries the list price and the confidentiality of the discount; section 1 carries the recommendation with managed access and the reasons for the equity premium.
2. NICE — resource impact report for TA1044. Source of the eligibility funnel, of the 1,794 eligible, of the year-by-year projection and of the justification of low uptake by the long hospital stay.
3. NICE — guidance TA1003, exagamglogene autotemcel for transfusion-dependent beta-thalassemia, published on September 11, 2024.
4. NICE — resource impact report for TA1003. Source of the 475 eligible and of the projection of 14 treatments in the first year.
5. ICER — assessment of gene therapies for sickle cell disease, 2023. Source of the price reference range of US$ 1.35 to 2.05 million, calculated before approval and before any announced price.
6. Zemplenyi A et al., 2025 — payment models for sickle cell disease gene therapies in Medicaid. Source of the standard-of-care cost in Colorado, of the cumulative balance over 6 years and of the American list prices. Pharmacoeconomics.
7. CMS — cell and gene therapy access model: 33 states, the District of Columbia and Puerto Rico, announced on July 15, 2025, covering 84% of Medicaid beneficiaries with sickle cell disease.
8. Chetlapalli K et al., 2026 — haploidentical transplant, gene therapy and standard of care in sickle cell disease: cost-effectiveness analysis. Source of the quality-adjusted life years, of the costs of the three strategies, of the 10,000 iterations and of the price ceiling per country. Blood.
9. GBD 2021 Sickle Cell Disease Collaborators, 2023 — global, regional and national prevalence and mortality burden of sickle cell disease, 2000-2021. Lancet Haematol 10(8):e585-e599.
10. Kliegman M et al., 2024 — a roadmap for affordable genetic medicines. Source of the proposal to cut the cost per patient tenfold. Nature.
11. Hmaidan S et al., 2025 — safety, feasibility and fertility preservation outcomes in patients with sickle cell disease and beta-thalassemia undergoing gene therapy. Source of the 17 of 17 with ovarian failure. Transplant Cell Ther.
12. Decree No. 7,646, of December 21, 2011 — article 15: the application for incorporation into the SUS requires the number and validity of the registration, scientific evidence, comparative economic evaluation and the price set by CMED.
13. CONITEC — Recommendation Report No. 924, Clinical Protocol and Therapeutic Guidelines for Sickle Cell Disease, 2024. Source of the 4% with sickle cell trait, of the 5,428 newborns diagnosed from 2014 to 2018, of the 84% newborn screening coverage and of the quotation on the absence of recent data.

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