Rare Disease, Real Threat: Tackling Cold Agglutinin Disease

Almost everyone knows someone living with a serious chronic condition like diabetes or high blood pressure, and knows how those illnesses can have a major effect on daily life.

Few people have heard of cold agglutinin disease (CAD), a rare and severe, autoimmune condition where the body attacks and destroys its own red blood cells. Yet for the estimated 10,000 patients in the US and Europe living with the disease – and more in other parts of the world – the disease is completely life-changing.

“I’ve gone from being very active on a regular basis to some days when I can barely walk to my own car without losing my breath,” said Jodie, who has been diagnosed with CAD. “This impacts everything about my life.”

In fact, cold agglutinin disease is far more serious than previously thought. A study just released by Bioverativ, a Sanofi company, analyzed patient registry data for 72 people with CAD and found that people with CAD are more than twice as likely to die in the first five years after diagnosis when compared to the general population. It also showed that people with CAD are at an increased risk of thromboembolic events, which are blood clots that can include life-threatening events like heart attack and stroke.

“These data show that greater understanding is needed about the risks associated with cold agglutinin disease, and reinforce the pressing need for an approved and targeted treatment for this life-threatening condition,” said Jaime Morales, MD, FAAP, Executive Director, Medical, Bioverativ.

Red Blood Cells Become Targets for Destruction

Antibodies act as a signal to the immune system to attack the cells to which they are attached, a normal and necessary immune function of the body to fight infections, for example. In people with CAD, an individual’s body begins to generate antibodies against its own healthy red blood cells, continually destroying large numbers of them in a process called hemolysis.

This causes people with CAD to suffer from chronic anemia that saps their energy. It also creates circulatory problems, particularly in the extremities like hands and feet, that makes them hyper-sensitive to cold. That affects everything from their diet to how they manage what should be normal, daily activities like going into air-conditioned spaces and eating cold food.

The disease is frequently not recognized or misdiagnosed, in part because it is so rare and in part because people tend to ignore early symptoms. People with CAD are typically diagnosed rel="noopener noreferrer" in their 60s, when the incidence of anemia tends to increase, so it can be discounted as just anemia or a part of aging.

“What this new study shows is that the increased mortality associated with CAD starts as early as the first year after diagnosis,” Morales says. “This makes early diagnosis and targeted treatments even more crucial for all people with CAD.”

Seeking an Effective Treatment

Today, there are no approved treatments for CAD. Disease management may include frequent blood transfusions to replace a patient’s red blood cells, but any improvement is short-lived as the person’s antibodies soon bind to the transfused red cells. The transfusion can also accelerate the immune response, as they are “really just feeding the disease and not addressing the underlying hemolysis,” says Morales.

Late-stage studies are underway now at Bioverativ on a potential treatment for the condition. The FDA awarded it “breakthrough” status based on the results from a Phase 1b clinical trial. This treatment was developed to specifically target the immune system at C1s in the classical complement pathway, the place where the red blood cell destruction starts. It’s important to note that this is an investigational treatment, and its safety and efficacy has not been fully evaluated by any regulatory authority.

Just the potential of a therapy targeted to treat CAD and stop the red blood cell destruction where it starts is a welcome development to people like Jodie.

“If there’s a treatment out there that would help with this disease and improve the quality of life, it would be a tremendous impact,” Jodie says. “It doesn’t affect a ton of people, but for those people, you’ll just make life so much better.”