CSL is investigating two potential new treatments for sickle cell disease:
- An injected monoclonal antibody designed to prevent pain crises by reducing the neutrophil levels in the blood: Researchers are studying whether the monoclonal antibody treatment can decrease the number of pain crises and reduce the chances of long-term injury to organs. Visit the TRANSCENDING trial site.
- A form of plasma-derived hemopexin, a naturally occurring protein produced in the body but found in decreased levels in patients with sickle cell disease: Researchers are studying hemopexin for the treatment of vaso-occlusive crisis, a severe and painful complication. Visit the RHEMEDY trial site.
For a condition that affects millions worldwide, treatment progress for sickle cell disease (SCD) has been slow. In the United States alone, an estimated 100,000 people are living with the disease, which can shorten life expectancy by approximately 20 years, according to the Centers for Disease Control and Prevention. The most severe form, sickle cell anemia, is also a leading cause of stroke in children.
People with sickle cell disease live with the ongoing risk of pain crises—sudden, severe episodes of pain—and long-term complications such as organ damage. These complications stem from a complex set of processes in the blood.
In SCD, normally round red blood cells take on a crescent, or “sickle,” shape. These misshapen cells can stick together and block blood flow through small blood vessels, reducing oxygen delivery to tissues and causing intense pain. But the disease is more than just a problem of misshapen cells.
“Sickle cell disease is often oversimplified as cells getting ‘stuck’ in the blood vessels,” said Dr. Greg Kato, a hematologist with more than 30 years of experience caring for people with SCD. “In reality, it involves a cascade of biological processes, including inflammation, cell damage, and the release of harmful substances into the bloodstream.”
One such substance is heme, which is released when red blood cells break down—a natural process that occurs more rapidly in people with SCD. Excess heme can contribute to inflammation and worsen disease complications. At the same time, certain immune cells, such as neutrophils, can become overactive and contribute to blood vessel blockage.
Recognizing this complexity, CSL is investigating two complementary approaches to address sickle cell disease—one aimed at preventing pain crises before they occur, and another focused on helping the body recover more quickly once a crisis begins.
Preventing pain crises before they start
One investigational approach targets neutrophils, a type of white blood cell that typically helps fight infection. In people with sickle cell disease, neutrophils can become activated even in the absence of infection, becoming “sticky” and adhering to blood vessel walls and other blood cells. This contributes to blockages that trigger pain crises and can lead to long-term organ damage.
CSL is studying an investigational monoclonal antibody, anumigilimab, designed to prevent neutrophil activation. By reducing this cellular “stickiness,” researchers hope to stop pain crises before they begin.
This approach is being evaluated in the TRANSCENDING clinical trial, which is examining whether treatment with anumigilimab can reduce the number of pain crises experienced by people living with SCD.
“Pain crises are the number one cause of emergency room visits for people with sickle cell disease,” said Dr. Paul Shore, a pediatric emergency and critical care physician and CSL clinical program director. “Preventing these crises could help reduce not only pain, but also long-term complications caused by reduced oxygen flow to vital organs.”
Helping resolve pain crises more quickly
A second investigational approach focuses on helping the body manage the aftermath of red blood cell breakdown during a pain crisis.
When red blood cells break apart, they release heme into the bloodstream. In healthy individuals, a naturally occurring protein called hemopexin binds to excess heme and helps clear it from the body. However, people with sickle cell disease often have lower levels of hemopexin, limiting this protective mechanism.
CSL is studying a plasma-derived form of hemopexin, known as CSL889, to help restore this function. By clearing excess heme, researchers hope to reduce inflammation and support faster recovery from pain crises.
This approach is being evaluated in the RHEMEDY clinical trial, which is assessing whether CSL889, given alongside standard treatment, can help resolve pain crises more quickly and improve overall health outcomes.
“Developing treatments for sickle cell pain crises is critical for delivering relief to patients suffering from debilitating pain,” Dr. Shore said.
Addressing the full burden of disease
Pain crises – also known as vaso-occlusive crises – can be unpredictable and profoundly disruptive. They may last from hours to several days and can occur without warning. Many patients describe the pain as severe and difficult to communicate, and it is sometimes not fully recognized in healthcare settings.
“A pain crisis feels like having a broken bone that’s not treated,” one patient shared with us. “It can start suddenly, even waking you from sleep, or build gradually over time.”
By targeting both the causes and consequences of these crises, CSL’s dual research strategy aims to address the full burden of sickle cell disease—from preventing episodes to helping patients recover more quickly when they occur.
Together, these efforts reflect a broader commitment to advancing care for people living with SCD and improving both immediate relief and long-term outcomes.
Learn more about the TRANSCENDING and RHEMEDY clinical trials
Kato and team will attend the Sickle Cell Disease Scientific Meeting and present on June 7 from 4-5:30 p.m. EST and June 8 from 9-9:15 a.m. EST.
