A pain crisis feels like having a broken bone that's not treated
For the roughly 100,000 Americans whose lives are shaped by the unpredictable violence of sickle cell disease, the promise of medicine has long lagged behind the reality of suffering. CSL, a global biotechnology company, is now pursuing two simultaneous clinical strategies — one to prevent the pain crises that drive patients to emergency rooms, and one to accelerate recovery when those crises cannot be stopped. In doing so, the company is acknowledging what patients have long known: that sickle cell disease is not a single problem, but a cascade of biological failures demanding more than a single answer.
- Sickle cell disease shortens life by roughly two decades and sends patients to emergency rooms more than almost any other blood disorder — the urgency for better treatment is not abstract, it is measured in years and crises.
- The disease operates on multiple fronts at once: misshapen cells block vessels, immune cells turn hyperactive, and the toxic byproduct heme floods the bloodstream when red blood cells break down faster than the body can clear them.
- CSL is testing anumigilimab in the TRANSCENDING trial to calm overactive neutrophils and prevent the cellular adhesion that triggers pain crises before they begin.
- A second trial, RHEMEDY, is evaluating CSL889 — a plasma-derived hemopexin — to restore the body's natural ability to clear heme and reduce the inflammation and organ damage that follow a crisis.
- Together, the two trials represent a strategic shift from managing symptoms toward interrupting the disease's full biological chain — prevention on one end, accelerated recovery on the other.
Sickle cell disease does not announce itself gently. Red blood cells warp into crescents, jam against vessel walls, and starve tissues of oxygen. Pain arrives without warning — sometimes in the middle of sleep — and can persist for days. For the 100,000 Americans living with the condition, these crises are not rare events but a defining rhythm of life, and they are the leading reason sickle cell patients seek emergency care.
Hematologist Dr. Greg Kato, with more than three decades of experience treating the disease, describes a biological failure far more complex than misshapen cells alone. Inflammation cascades through the bloodstream, immune cells become hyperactive, and the breakdown of red blood cells releases heme — a toxic byproduct that drives further damage. The disease shortens life expectancy by roughly twenty years and remains a leading cause of stroke in children.
CSL is now pursuing two distinct but complementary strategies to interrupt this chain of harm. The first, tested in the TRANSCENDING trial, investigates anumigilimab — a monoclonal antibody designed to reduce the abnormal stickiness of neutrophils, the white blood cells that adhere to vessel walls and trigger blockages. The goal is to prevent crises before they begin.
The second strategy addresses what unfolds once a crisis is already underway. Sickle cell patients typically have depleted levels of hemopexin, the protein that binds and clears excess heme from circulation. Without it, inflammation lingers and recovery slows. The RHEMEDY trial is evaluating CSL889, a plasma-derived hemopexin, to restore this protective mechanism and reduce the long-term organ damage that accumulates over years of repeated crises.
One patient described the pain as feeling like an untreated broken bone — sudden, severe, and often invisible to those around them. Dr. Paul Shore, a pediatric emergency physician and CSL clinical program director, frames the stakes directly: preventing crises would not only ease immediate suffering but slow the organ damage that quietly shortens lives. For millions of people worldwide, these two trials represent something the disease has rarely received — a strategy aimed at its full weight, not merely its surface.
Sickle cell disease moves through the body like a cascade of failures. The red blood cells warp into crescents and jam against vessel walls. Oxygen starves the tissues. Pain arrives suddenly, sometimes in the middle of sleep, and it can last for days. For the roughly 100,000 Americans living with the condition, these crises are not rare interruptions—they are the rhythm of survival. They are also the reason more sickle cell patients end up in emergency rooms than patients with almost any other blood disorder.
What makes the disease so difficult to treat is that it is not, as Dr. Greg Kato explains, simply a problem of misshapen cells. Kato, a hematologist with more than three decades of experience treating sickle cell patients, describes a far more intricate biological failure: inflammation cascades through the bloodstream, immune cells become hyperactive, and when red blood cells break down—which happens faster in sickle cell patients than in healthy people—they release heme, a toxic byproduct that fuels further damage. The disease shortens life expectancy by roughly two decades. In children, it is a leading cause of stroke.
CSL, a global biotechnology company, is now pursuing two distinct but complementary approaches to interrupt this chain of harm. The first targets the crisis itself. The company is investigating anumigilimab, a monoclonal antibody designed to calm neutrophils—a type of white blood cell that, in sickle cell patients, becomes abnormally "sticky" and adheres to blood vessel walls, triggering blockages and pain. By reducing this cellular adhesion, researchers hope to prevent crises from starting in the first place. This work is being tested in the TRANSCENDING clinical trial.
The second approach addresses what happens after a crisis begins. When red blood cells break apart during a pain episode, they flood the bloodstream with heme. Healthy people produce hemopexin, a naturally occurring protein that binds to excess heme and clears it from circulation. But sickle cell patients typically have lower hemopexin levels, leaving them vulnerable to prolonged inflammation and slower recovery. CSL is studying CSL889, a plasma-derived form of hemopexin, to restore this protective mechanism. The RHEMEDY trial is evaluating whether this treatment, given alongside standard care, can help patients recover more quickly from pain crises and reduce long-term organ damage.
Dr. Paul Shore, a pediatric emergency physician and CSL clinical program director, frames the stakes plainly: pain crises are the number one reason sickle cell patients seek emergency care. Preventing them would not only ease immediate suffering but also reduce the organ damage that accumulates over years of reduced oxygen flow. One patient described a pain crisis as feeling like "a broken bone that's not treated"—sudden, severe, and sometimes impossible to communicate to healthcare providers who may not fully recognize its severity.
The dual strategy reflects a recognition that sickle cell disease cannot be solved by addressing a single mechanism. The disease is a knot of biological failures: cell shape, immune activation, inflammation, heme toxicity, organ damage. CSL's approach is to pull at two different threads simultaneously—preventing the crisis and accelerating recovery when prevention fails. For millions of people worldwide living with a condition that has historically received slow treatment progress, these two trials represent a shift toward addressing the full weight of the disease rather than its symptoms alone.
Notable Quotes
Sickle cell disease is often oversimplified as cells getting stuck in blood vessels. In reality, it involves a cascade of biological processes, including inflammation, cell damage, and the release of harmful substances into the bloodstream.— Dr. Greg Kato, hematologist
Pain crises are the number one cause of emergency room visits for people with sickle cell disease. Preventing these crises could help reduce not only pain, but also long-term complications caused by reduced oxygen flow to vital organs.— Dr. Paul Shore, pediatric emergency physician and CSL clinical program director
The Hearth Conversation Another angle on the story
Why does sickle cell disease cause pain crises specifically? What's happening in the body at that moment?
The misshapen cells get stuck in small blood vessels and block blood flow. But it's not just the shape—neutrophils, which are immune cells, become overactive and "sticky." They adhere to the vessel walls and to each other, making the blockage worse. When oxygen can't reach the tissues, you get severe pain.
And the heme that gets released—why is that such a problem?
When red blood cells break down faster than normal, heme spills into the bloodstream. In a healthy person, hemopexin catches it and clears it out. But sickle cell patients don't have enough hemopexin. The heme stays in circulation and triggers inflammation, which makes everything worse and prolongs the crisis.
So CSL's two treatments are attacking the problem from opposite directions.
Exactly. One stops the crisis before it starts by calming the neutrophils. The other helps the body clean up the damage once a crisis is underway. Together, they address both prevention and recovery.
Why hasn't this been solved before? The disease has been known for a long time.
Treatment progress has been slow. The disease is genuinely complex—it's not just one broken thing. It took time to understand all the biological processes involved. Now that researchers like Dr. Kato have mapped out the cascade, companies like CSL can target specific points in that cascade.
What does a pain crisis actually feel like for patients?
Unpredictable. Severe. One patient said it feels like having a broken bone that's not treated. It can wake you from sleep or build gradually. It can last hours or days. And sometimes healthcare providers don't fully recognize how serious it is because it's hard to communicate the pain.
If these trials work, what changes?
Fewer emergency room visits. Less organ damage over time. Longer, less disrupted lives. For people living with a disease that shortens life expectancy by twenty years, that's everything.