Sickle cell disease (SCD) is the most common inherited blood disorder in the United States. It affects about 100,000 children and adults in the United States and millions of people worldwide.
New treatments are needed to prevent and treat its serious complications. That’s why the U.S. Food and Drug Administration is working with patients and stakeholders, including academics and those from the pharmaceutical industry, to help.
What Is Sickle Cell Disease?
Sickle cell disease affects millions of people worldwide and is particularly common among people with ancestors from sub-Saharan Africa; Spanish-speaking regions in the Western Hemisphere (South America, the Caribbean, and Central America); Saudi Arabia; India; and Mediterranean countries such as Turkey, Greece, and Italy, according to the Centers for Disease Control and Prevention.
More than 3 million Americans, including one in 13 African Americans, carry the sickle cell trait, the gene that can potentially allow the disease to be passed on to their children. A baby born with sickle cell disease must inherit a SCD gene from each parent. Babies born in the United States are typically screened at birth for SCD.
People with the disease have “sickled” or abnormally shaped red blood cells that get stuck in small blood vessels and block the flow of blood and oxygen to major organs in the body. These blockages can cause severe pain, organ damage, or even stroke. Other complications include vulnerability to infection, fatigue, and delayed growth.
SCD is chronic and its severity varies. Most people with the disease will have shortened lifespans.
How Is Sickle Cell Disease Treated?
Until recently, patients with SCD only had one drug treatment option: hydroxyurea, which the FDA originally approved in 1998 for adults only. This medication helps red blood cells to stay round and flexible, which can help reduce complications. Common side effects of hydroxyurea include low blood counts, gastrointestinal symptoms, and loss of appetite.
In July 2017, the FDA approved Endari (L-glutamine oral powder) to reduce acute complications of sickle cell disease, including the frequency of sudden, severe attacks of pain (called sickle cell crises). This product is for patients age 5 and older and was the first new treatment in nearly 20 years. Common side effects of Endari include constipation, nausea, headache, abdominal pain, cough, pain in the extremities, back pain, and chest pain.
And in December 2017, the FDA approved hydroxyurea to reduce the frequency of painful crises and the need for blood transfusions in patients age 2 and older who have sickle cell anemia with recurring moderate to severe painful crises. This was the first FDA approval of hydroxyurea for use in children with the disease.
But treatments are still limited.
Bone marrow or stem cell transplants may be an option for younger patients with severe SCD. But serious and potentially life-threatening side effects can accompany these expensive procedures. These transplants also require finding a matching bone marrow or stem cell donor, which can be difficult. So most people cannot receive these transplants.
Blood transfusions can treat anemia, a common complication of SCD. Patients often receive transfusions regularly and over the long-term to prevent complications.
“The majority of patients with SCD are treated with hydroxyurea, pain medication, and chronic blood transfusions and are hospitalized when crises occur,” explains Ann T. Farrell, M.D., director of the FDA’s Division of Hematology Products within the Center for Drug Evaluation and Research.
“Unfortunately, some treated patients will have no reduction of their symptoms and the disease will continue to progress,” Farrell adds. “Better therapies are desperately needed.”
How Is the FDA Encouraging New Treatments?
Working with stakeholders
The FDA continues to work with stakeholders—including patients, academics and companies developing treatments—to improve therapeutic options for people living with SCD.
A growing number of new products are in the pipeline, and researchers are exploring new treatment approaches. “These potential treatments are in different stages of development, including early and late clinical trials,” Farrell says. (Clinical trials are voluntary human research studies designed to answer specific questions about the safety and effectiveness of potential new treatments—or to study new ways of using existing treatments.)
Companies developing sickle cell products can ask the FDA to grant a “fast track” designation, a type of regulatory status that seeks to bring new products to market faster. “This allows for early and more frequent interactions with the FDA to discuss any issues that come up during development, such as manufacturing and trial design,” Farrell explains.
If preliminary data show potential promise over existing therapies, companies also can request “breakthrough therapy designation” to speed the development and review of products.
The FDA also can encourage the development of new SCD treatments by giving certain drugs and biological products “orphan status.” (This designation is possible for products intended to treat rare diseases affecting fewer than 200,000 people in the United States per year. These sponsors can qualify for incentives like tax credits and marketing exclusivity.)
Because SCD is a global issue, the FDA encourages the pharmaceutical industry to develop treatments internationally. Now, companies are conducting clinical trials not only in the United States, but also in Europe and Africa.
Meeting with patients
“Learning the patient perspective—what symptoms bother them the most and where they would like to see treatments to focus—is important in the development of new therapies,” Farrell explains. “In the past, patients said the symptoms that matter most to them in terms of their disease are acute and chronic pain, stroke, fatigue, and sleep disturbances. Patients also said they are willing to participate in clinical trials to identify new treatments.”
The FDA’s Division of Hematology Products considers the development of new sickle cell disease treatments a priority.
“We will continue to work with sponsors as much as possible to help remove roadblocks to new product development,” Farrell says. “We feel for these patients because they have to live with the devastating consequences of this chronic condition. It’s important for the FDA to help as much as we can.”