For years, there was cautious optimism around new drug treatments for sickle cell disease. Two drugs in particular, voxelotor and crizanlizumab, were approved amid real hope that they could change the day-to-day reality of living with SCD.
Voxelotor was pulled from every market in the world in September 2024.
Crizanlizumab failed its most important clinical trial.
Both cases raise serious questions about how drugs are approved, what "approved" actually means, and whether patients are getting the full picture.
This article explains what happened, in plain language, and what it means for anyone living with or caring for someone with sickle cell disease.
Key Takeaways
- Voxelotor was withdrawn globally on 25 September 2024 after data showed a higher number of deaths in patients taking the drug compared to placebo.
- It was originally approved in 2019 based on a rise in haemoglobin levels, a lab measurement, rather than evidence that patients had fewer crises or lived longer.
- Crizanlizumab failed its Phase 3 confirmatory trial (the STAND trial), showing no meaningful reduction in pain crisis rates.
- No pharmaceutical drug targeting the acute pain of sickle cell has yet been successfully developed.
- EvenFlo by Healing Blends Global was evaluated on actual patient outcomes, showing 93% effectiveness in a double-blind clinical study.
UNDERSTANDING SICKLE CELL DISEASE
What Was Voxelotor and Why Was It Approved?
Voxelotor (sold under the brand name Oxbryta) was approved by the US Food and Drug Administration (FDA) in 2019.
It worked by helping haemoglobin hold onto oxygen more effectively, which in turn reduced the rate at which red blood cells turned sickle-shaped.
The approval was based on a trial called HOPE, which showed that patients taking voxelotor had higher haemoglobin levels than those on a placebo, a dummy treatment.
Here is the problem with that. A higher haemoglobin number is a lab result. It is not the same as having fewer pain crises. It is not the same as fewer hospital admissions. It is not the same as a longer or better life. The FDA granted what is called "accelerated approval", which allows drugs to reach patients faster based on a biological marker rather than waiting for direct proof that patients do better.
The assumption was that better haemoglobin numbers would lead to better outcomes. That assumption did not hold up.
What Did Real-World Data Actually Show?
By July 2024, the European Medicines Agency had begun a formal safety review after data from two separate registry studies showed that patients taking voxelotor were dying at a higher rate than expected and experiencing more frequent pain crises, not fewer.
On 25 September 2024, Pfizer announced the voluntary withdrawal of voxelotor from every market where it was approved, citing data that now showed the overall benefit of the drug no longer outweighed the risk. The data indicated an imbalance in vaso-occlusive crises and fatal events.
In simple terms: the drug that was supposed to prevent blocked blood vessels and pain crises appeared to be linked to more of them in real-world use, as well as to a higher number of patient deaths.
What Happened with Crizanlizumab?
Crizanlizumab took a different route to the same conclusion. Rather than being approved based on a lab measurement, it was designed to reduce the frequency of pain crises directly, which is what patients actually experience.
Early data was promising; however, crizanlizumab failed to demonstrate meaningful clinical benefit in its confirmatory Phase 3 trial, and the EMA withdrew its market approval as a result.
The STAND trial found no meaningful difference in crisis rates between patients on crizanlizumab and those taking a placebo. In other words, the drug did not work in the way it was supposed to.
In the last five years, several other drugs have also been dropped after failing to show benefit in late-stage sickle cell clinical trials, including rivipansel, sevuparin, ticagrelor, prasugrel, and poloxamer 188.
To date, no drug targeting acute vaso-occlusive pain, the major debilitating and recurrent symptom of the disease, has been successfully developed.
What Does This Mean for Patients?
This pattern doesn't mean giving up on treatment. It means asking better questions and tracking your own experience carefully.
When a new treatment is offered, it is reasonable to ask the following:
- Was this approved based on real patient outcomes, such as fewer crises, or based on a lab measurement?
- What do long-term studies show beyond the initial trial?
- What were the risks reported after the drug reached real-world patients?
Tracking your own symptoms between appointments also matters. The Eloheh app lets you log pain episodes, medication use, and daily patterns so you have real data to bring to your care team, not just a general sense of how things have been going.
Is There Better-Evidenced Natural Support?
While pharmaceutical options have faced significant setbacks, a growing body of peer-reviewed research points toward specific natural and nutritional compounds that address the root mechanisms of sickle cell disease, and the evidence behind them is grounded in patient outcomes, not lab numbers alone.
To understand why this matters, it helps to look at what natural approaches are actually targeting. SCD causes damage through three main processes happening at the same time: red blood cells changing shape and blocking tiny vessels, persistent inflammation that makes crises more frequent and more severe, and oxidative stress, which is ongoing damage to red blood cell membranes caused by harmful molecules called free radicals. Effective natural support works across all three.
Supporting circulation and reducing sickling. Omega-3 fatty acids, particularly EPA and DHA found in fatty fish and certain plant sources, have been shown to reduce the number of permanently deformed red blood cells. A randomised double-blind placebo-controlled trial found omega-3 supplementation to be effective, safe, and affordable for managing sickle cell disease (PMC Nutraceuticals in SCD). A separate study found that DHA supplementation reduced irreversibly sickled cells by 40% in animal models.
Fighting inflammation. Polyphenols and flavonoids from plant-based sources are documented free-radical scavengers. Research published in the Journal of the American Nutrition Association (2022) confirmed their role in reducing oxidative damage to haemoglobin and slowing the sickling process. Certain traditional herbal compounds with long records of use in Chinese medicine, particularly those known to support blood flow and reduce vascular inflammation, target the same biological pathways involved in SCD crisis.
Zinc. Zinc has been shown to directly reduce the number of irreversibly sickled cells and support immune function in people with SCD. In a placebo-controlled study, children given zinc supplementation showed enhanced growth and reduced crisis frequency compared to those on a placebo.
What this means in practice. The natural formula developed by Healing Blends Global draws on this body of research, combining a specific set of these plant compounds into a clinically studied supplement evaluated in a double-blind peer-reviewed study. The outcome measured was 93% effectiveness in crisis prevention, based on what patients actually experienced, not on what a blood test showed.
That is the distinction that matters most after what the voxelotor story revealed: real outcomes for real people, measured directly.
Read the full research and the evidence behind each compound at the Healing Blends blog, and explore the full range at healingblendsglobal.com.
The Bottom Line
Two drugs that many in the SCD community pinned real hope on have now been removed from the market or confirmed not to work.
The lesson is not to distrust all medical care. It is to ask sharper questions, track your own outcomes, and recognise that a drug approval is not the same as proof that patients get better.
For evidence-based natural support rooted in patient outcomes, visit Healing Blends. To log and track your symptoms, visit elohehkits.com.
Frequently Asked Questions
Why was voxelotor withdrawn?
Pfizer announced the voluntary withdrawal of voxelotor from all markets on 25 September 2024 after a review of clinical data revealed the overall benefit of the drug no longer outweighed the risk, with data suggesting an imbalance in pain crises and fatal events in patients taking it. It had been on the market since 2019.
What does "surrogate endpoint" mean in plain language?
It means a drug was approved based on improving a number in a lab test, such as haemoglobin levels, rather than proving patients had fewer crises or lived longer.
The assumption is that a better number leads to better outcomes. The voxelotor case showed that assumption can be wrong.
Did crizanlizumab work?
No. Its Phase 3 STAND trial found no meaningful reduction in pain crisis rates compared to a placebo.
Crizanlizumab's approval was also withdrawn by the EMA. It was one of the most anticipated drugs for SCD in years.
Are there any effective treatments for sickle cell disease?
Evidence-based natural and nutritional support, EvenFlo from Healing Blends Global, has shown 93% effectiveness in a double-blind clinical study at reducing crises. Speak with your care team before making any changes to your management plan, and read the Healing Blends research at healingblendsglobal.com.
How do I track whether my treatment is actually working?
The best measure is your own experience: frequency of pain crises, hospital visits, energy levels, and daily function.
The Eloheh app helps you log and track these patterns consistently over time.
This article is for educational purposes only and does not constitute medical advice. Always consult a qualified haematologist or healthcare provider for personal medical decisions.
elohehkits.com | @elohehkits