Casgevy and the Sickle Cell Crisis in America
Millions were spent developing a cure that costs $2 million, but most sickle cell patients don't even get routine care. What are we even doing here?
I hope you like the double entendre in the title.
The FDA approval of Casgevy and Lyfgenia made headlines last fall - these treatments brilliantly utilize CRISPR-Cas9 gene editing technology to “cure” sickle cell disease. Essentially, stem cells are taken from the patient and are modified using CRISPR, and these same host cells are given back to the patient as a single-dose IV infusion, almost like a hematopoietic stem cell transplant. These are the first-in-class gene therapies that have been approved by the FDA, and are by all means, a major scientific breakthrough in the treatment of genetic disease.
The data has been very promising as well. Per the press release, the two small-scale single-arm approval trials showed a 94% and 88% remission rate of vaso-occlusive crises within the follow-up period for Casgevy and Lyfgenia respectively.
In the US, these treatments would be indicated in sickle cell patients 12 years or older with recurrent vaso-occlusive crises and for patients with transfusion-dependent beta-thalassemia. However, the reason I say would be is because nobody on Earth is affording this medication. Casgevy has a staggering US list price of $2.2 million. That’s the cheaper option - Lyfgenia is $3.1 million.
This breakthrough did not come without some major investment either - the primary manufacturer Vertex made a $200 million milestone payment to CRISPR Therapeutics for the sale and distribution of Casgevy. While it is not listed online, I can only imagine the cost it took CRISPR Therapeutics to develop it in the first place.
Despite the fact that we now essentially have a cure for sickle cell, it remains severely undertreated among our nation’s youth, who are particularly at high risk of complication. I recently came across this article that details the horrendous state of long-term sickle cell management in the pediatric population. This was actually what inspired me to write this as I had heard news stories of Casgevy’s approval last year.
The study looked at Medicaid claims between 2010 and 2019 from California and Georgia and found that only one in five children under age 5 with sickle cell received daily antibiotic prophylaxis. Only half of 2-15 year olds studied received their annual transcranial ultrasound with Doppler.
This particularly astonished me given the extensive research and guidelines that are well-known surrounding the complex care that these patients need. Any third-year medical student can tell you that in addition to guideline-directed therapy, children under age 5 should receive penicillin prophylaxis to protect against infection from encapsulated organisms due to their functional asplenia. Children 2-16 years should be also screened annually with transcranial Doppler for stroke.
What was also saddening is that sickle cell is most prevalent in the African-American population (1 in 365), a community that has already been underserved by medicine. Lack of access to insurance and consistent medical follow up combined with exorbitant medical costs were likely driving factors in the disappointing findings. A recent study also found that the lifetime healthcare costs of having sickle cell disease top $1.5 million per person. All in all, the landscape for the mostly-minority sickle cell population seem nightmarish, and contribute further to worse health outcomes and mortality among America’s least fortunate.
So despite the fact that we now have a cure for sickle cell, an extremely well-understood disease with guidelines on mortality-improving care, few people actually obtain routine care and essentially nobody can obtain the cure. What sticks out to me most in this situation is the overtly asinine priorities of the pharmaceutical industry and FDA, which speaks broadly about a disturbing trend in medicine. Why is the private sector investing millions (that are partly subsidized by taxpayers through research and university endowments) to develop and approve groundbreaking drugs that nobody can get? Isn’t the goal of medicine and medical research to discover therapies that can be readily obtained and have the best net overall affect on people’s health outcomes? There is no point in inventing a shiny new Mercedes-Benz if nobody is allowed to drive it.
Could the millions spent on this unobtainable sickle cell therapy have been better utilized to improve social determinants of health of the sickle cell population? I argue yes. Think about a quality-control project such as reconciling a pediatric clinic’s records of patients with sickle cell, confirming that they are all on guideline-directed therapy and obtaining their indicated screens, and documented the patients’ next visits and setting aside time for patient education and addressing any barriers to care. If even a quarter of the clinics in the country did that, I am sure we would see a much greater net health and mortality benefit in the US sickle cell population than the approval of this $2 million dollar drug.
In my opinion, we also need to completely redefine what a “breakthrough” means in medical research. This responsibility falls under the purview of the FDA, as the treatments they approve define what constitutes enough of a “breakthrough” to merit acceptance into the market. Prior approvals signal to researchers and companies alike on the FDA’s priorities and how to guide further study. Now I do not want to undermine the remarkable achievement of developing CRISPR-Cas9 technology - which will shape treatments of genetic disease in the decades that come. This work fully deserved the Nobel Prize in 2020. It is also common knowledge that cutting edge treatments are very expensive and it takes further research and development to bring the cost lower and provide ubiquitous access.
However, I simply argue that treatments of this nature should not be approved by the FDA and brought to market until it can be proven that it can be offered at a more reasonable price and can be fairly accessible. FDA should turn their eye from drugs like Casgevy towards other drugs that may not be as biologically-groundbreaking, but improve outcomes and can be used by many afflicted patients upon its release. When CRISPR technology develops to the point that Casgevy can be used more broadly in routine care, I will be the first one to welcome it with open arms.