By Sanius Health
It’s been an amazing but in some parts disappointing summer. Over the course of a hundred years of scientific progress in sickle cell disease and innovations in gene therapies, we have yet to see an extraordinary impact for patients.
The molecular story has been extraordinary, from the first description of sickled cells in 1910 to gene therapies now reaching patients.
But sit with the more uncomfortable version of that story and a pattern emerges: a run of promising programmes that have failed to differentiate, been discontinued, run into regulatory trouble or been withdrawn outright.
After more than a century of study, why does turning that understanding into medicines that reach and stay with patients remain so hard?
A summer of setbacks
Two recent developments make the point, and they are not the same kind of failure.
In July 2026, development of tebapivat in sickle cell disease was discontinued, but not because it failed biologically.
Haemoglobin response rates of 43.8 per cent, 47.1 per cent and 29.4 per cent across three doses, against 33.3 per cent on placebo, confirmed pyruvate kinase activation works as a therapeutic mechanism.
What the trial did not do was separate tebapivat clearly enough from a more advanced candidate in the same class, mitapivat, now under FDA Priority Review.
That is a commercial judgement as much as a scientific one: a medicine that works but fails to differentiate is a different problem to one that does not work at all.
Then there is Oxbryta (voxelotor).
Withdrawn globally in September 2024 after trial and registry data showed more vaso-occlusive crises and deaths among patients taking it than expected, two further years of reanalysis with the US regulator followed, seeking a route back to market.
In August 2026 that route was closed: the conclusion, communicated directly to the sickle cell community, was that there is no viable path back to the United States.
Crizanlizumab is a related but distinct story.
Approved on Phase 2 data in 2019, it failed to beat placebo on its primary endpoint in the confirmatory Phase 3 STAND trial, losing its EU authorisation in 2023 and UK licence in January 2024, though it remains available in the United States, where regulators reached a different judgement on the same data.
None of these is simply “another failed sickle cell drug,” and treating them as interchangeable obscures more than it reveals.
One is a strategic discontinuation of a working mechanism. One is a safety-driven withdrawal two years of analysis could not reverse. One is a confirmatory trial that overturned an earlier positive signal, with regulators still disagreeing about the result.
Each raises a related question: what does it say about how we develop medicines for this disease that promising signals so often fail to hold up?
The cost of getting it wrong
For industry, a discontinued programme or withdrawn licence means capital, years and opportunity lost. For patients, every delay is measured in pain crises, organ damage and years of life that do not come back.
Global Burden of Disease modelling puts the scale in stark terms: 7.74 million people were living with sickle cell disease worldwide in 2021, up 41 per cent since 2000.
Cause-specific deaths were recorded at 34,400, but total mortality attributable to the disease is estimated at 376,000 a year, including more than 81,000 children under five.
Roughly three-quarters of that burden falls on sub-Saharan Africa. In the UK, cohort data shows adult life expectancy still trails the general population by decades; in the US, median survival has risen from the low forties in the 1990s to around 58 by 2014. Patients in Britain and America, for all these gaps, still have access most of the world does not.
An evidence problem, not just a drug problem
Part of what these setbacks expose is how thin our understanding still is of what happens between clinical encounters. Trials measure haemoglobin and hospital-recorded crises at scheduled visits.
They rarely capture the pain and fatigue managed quietly at home, or whether a biological improvement translates into a life someone experiences as better.
Incomplete natural-history data, fragmented trial populations and episodic rather than continuous measurement all make it harder to know, early, whether a signal is real.
Perhaps the way we observe this disease has simply not kept pace with the therapies we are now trying to develop for it.
Across Sanius Health’s ecosystem, longitudinal patient-reported outcomes, wearable and physiological data, self-reported crises and healthcare utilisation build a fuller picture before, during and after trials.
Not a substitute for clinical development, but a way of closing the distance between what a trial sees and what a patient lives.
Before a study starts, that means natural-history datasets rich enough to inform patient stratification and more meaningful endpoints, rather than ones inherited from smaller, older studies.
During a trial, it means continuous monitoring of pain, fatigue, sleep and physiological signals alongside the traditional clinical endpoints, so a research team can see whether a biological improvement shows up in how a patient feels between visits, not only in their bloodwork at the next one.
After approval, it means longitudinal real-world evidence on effectiveness, safety and adherence gathered over months rather than reconstructed from hospital coding after the fact.
And across geographies, it means building more representative evidence from the populations, in Africa, India and Brazil, that trials have historically under-represented, where the burden is heaviest and the evidence thinnest.
A hospital record tells a researcher what happened when somebody reached hospital. It says little about the weeks in between, where most of a patient’s life with this disease is actually lived.
None of this predicts which programme will succeed. What better longitudinal evidence can do is narrow the uncertainty a company operates under and give researchers a fuller account of how a therapy performs in the people taking it.
We have spent a century getting better at the biology of sickle cell disease. The next task is getting equally serious about the lived biology of the patient.
The answer to repeated setbacks is not less investment; it is better evidence around the investment already being made.
Patients cannot afford another century of trial and error.
Learn more about Sanius Health at saniushealth.com
