The treatment of sickle cell disease is on the cusp of a historic breakthrough, with makers of two gene-based treatments for the debilitating blood disorder hoping for regulatory approval this year.
But for those with sickle cell in sub-Saharan Africa, where more than 60% of the 120 million people worldwide live with this disease, there is little cause to celebrate. A potential cure that could save them from severe illness and early death will exist — but its expected multimillion-dollar price tag will be far out of reach.
Sickle cell disease throws the issue of access to health care into particularly stark relief because it is a major cause of early death and disability among some of the world’s most deprived populations, from Africa to Black communities in the U.S.
The vast majority of those affected by the genetic disorder — in which misshapen blood cells cause anemia, organ damage, severe pain, stroke, and early death — have African ancestry. Indeed, according to the World Health Organization, around 1,000 babies are born every day in Africa with two copies of the sickle hemoglobin gene that causes the disorder, and more than half of them will likely die before they reach the age of 5.
The good news is there has been remarkable progress in recent years in both gene therapy and the newer field of genome editing. As a result, medics are now able to deploy genetic tools to cure once incurable diseases — from some forms of blindness to rare childhood disorders — and clinical trials suggest that dozens of new treatments could reach the market in the next decade. However, the new science will only truly benefit humanity if it is widely accessible.
The companies behind the two new sickle cell treatments — Bluebird Bio, which has developed a gene therapy, and a partnership between CRISPR Therapeutics and Vertex Pharmaceuticals, which uses the genome-editing tool CRISPR — have yet to set a price for their products. But the expectation is that these therapies will cost more than $2 million per patient, in line with U.S. prices for existing gene therapies for other diseases of $1 million to $3.5 million.
Prices of this magnitude are unsustainable if gene therapy is to move beyond treating just a handful of patients.
Ensuring access for complex treatments even rich countries struggle to afford will not be easy, but this is even more reason for pharmaceutical companies, governments, and the global health care community to start working now on ways to bridge the access gap.
This is in addition to the obligation on pharmaceutical companies to do more to help patients today, even as they plan for the future. In the case of sickle cell disease, Africans are already falling far behind when it comes to accessing an important existing drug, hydroxyurea, which is not a cure but can improve survival by up to 80%. The disparity in access to this chemotherapeutic agent, whose benefits have been known for two decades, is one of the key reasons why African patients die so much earlier than those in the U.S., where 85% of patients receiving treatment survive until adulthood. (In another sign of neglect, research on average life expectancy for Africans with sickle cell disease is limited.) But it’s not the only reason: Patients in the U.S. have access to early diagnosis, including newborn screening, as well as bone marrow transplants and other treatments.
It’s been clear for some time now that these treatments are on the cusp of approval. But so far, I have seen limited signs that the companies involved are designing ways to enable access at scale for people in low- and middle-income countries, save for Novartis’ sickle cell program, which also has its challenges.
As the CEO of the Access to Medicine Foundation, I find the lack of a comprehensive approach from all companies who develop treatments that will benefit few both disappointing and predictable.
All too often, society considers access far too late in the game, instead of ensuring access plans are in place when products are still in development. The result is unacceptable gaps in care — for example, in cancer where treatment in low- and middle-income countries is only now a priority after years of neglect.
To date, gene therapy has only been approved for very rare conditions. But sickle cell disease is in a different league, since it affects at least 120 million of people around the world. The novel gene treatments developed to correct the mutation responsible for the condition are intended as one-time cures, making them potentially transformative, yet that transformation will never happen if the cost is prohibitive.
The experience with other pioneering medical technologies, like monoclonal antibodies, suggests that costs will come down as production increases. But there also needs to be appropriate planning from the earliest stages.
Importantly, we need innovation in how gene-based treatments are delivered into the body. Current treatment regimens involve manipulation of a patent’s cells outside their body, followed by intensive hospital care, which requires sophisticated medical infrastructure that is unavailable in most of sub-Saharan Africa.
To make gene-based cures affordable in low-resource settings, they will ultimately need to be delivered in a simpler, cheaper manner. Novartis has recognized the importance of this and is working with the Bill & Melinda Gates Foundation on an ambitious project to deliver gene medicines in vivo — or directly into the body — instead of via the current complex ex vivo process. So far, the in vivo work is aspirational, and it remains to be seen if it can be made to work in practice.
Such technical advances can certainly improve equitable access. But it’s also critical to foster a new mindset so that knowledge is transferred between nations. Rolling out a new generation of sickle cell cures without a strategy to get them to those populations with the greatest need is not acceptable.
The genetic revolution offers a tantalizing glimpse of a future free from sickle cell disease. It must not be exclusive preserve of a small number of patients in rich countries. Science without access is science fiction — and gene therapy should not be a fiction to millions who need it.
Jayasree K. Iyer is the CEO of the Access to Medicine Foundation.