New Medications at Last for Sickle Cell Disease
It all starts with a mutated gene. If you inherit two copies – one from each parent – the red blood cells that carry oxygen throughout your body may turn into crescent shapes instead of smooth ovals.
These misshapen cells – the hallmark of sickle cell disease – can get stuck in blood vessels, causing episodes of intense pain.
Most sickle-cell pain is known as a vaso-occlusive crisis or acute pain crisis. It can affect any part of the body. Pain that occurs in the chest, along with shortness of breath, is called acute chest syndrome.
For people with sickle cell disease, most of whom are African American, incidents like these may come a few times a year or much more often. While these crises last, people may need hospital care as well as opioid medications to cope with the severe pain.
New Drugs Developed
But treatments can help reduce these threats, and in the last few years three effective new drugs have become available, say two Einstein Healthcare Network doctors who treat sickle cell disease.
“Compared to five, 10 years ago, when we only had one drug, I think it is encouraging,” says Mitchell Goldstein, MD, an Einstein hematologist (blood disease specialist) who treats many sickle cell patients.
“There is a lot of research going on right now,” he adds, “for other potential drugs to stop the sickling” – the distortion of red blood cells into a crescent or sickle shape.
“Hopefully in the long term a person will be able to get gene therapy, when you change the genes, but this is in a very pioneering state,” says Gabor Varadi, MD, another Einstein hematologist who treats sickle cell disease.
The crescent- or sickle-shaped red blood cells tend to break down quickly in the body, causing a shortage (anemia), so sickle cell disease is sometimes called sickle cell anemia.
Sickle cell also may lead to potentially deadly lung problems, blood clots, strokes, kidney failure, blindness and other serious health problems. The average life expectancy is about 50, decades below the U.S. average.
For decades, the standard treatment for sickle cell disease has been hydroxyurea. This drug increases hemoglobin (the substance in red blood cells that carries oxygen) and decreases the formation of sickle-shaped cells (sickling). As a result, hydroxyurea can reduce pain crises by about 50%.
When the number of sickle-shaped cells gets too high, people also may receive blood transfusions to increase the number of normal blood cells in the body.
The following new drugs offer further relief:
- L-glutamine (Endari), approved in 2017, is a powder that’s stirred into a drink and taken twice a day. It reduces acute pain crises by about 25%, Dr. Goldstein says.
- Voxelotor (Oxbryta), approved in 2019, is a once-daily pill that increases normal hemoglobin levels and decreases sickling. More studies are needed to show whether this reduces the number of pain crises, Dr. Goldstein notes.
- Crizanlizumab (Adakveo), approved in 2019, is a monthly injection given in a doctor’s office. In clinical trials that led to approval by the Food and Drug Administration, it reduced acute pain crises by almost 50%.
None of these medications has replaced hydroxyurea, but the doctors say they offer further relief for patients who need more.
“With hydroxyurea, you don’t want to stop at too low a dose,” Dr. Goldstein notes. “But if you’re giving the maximal dose and they still have these painful crises, now you have a choice of these three new treatments out there.“
“Sometimes I try to combine the L-glutamine with the hydroxyurea, when the hydroxyruea doesn’t reduce the number of painful crises enough, or if the patient does not want to take the hydroxyurea.” Dr. Varadi says. “For those patients who have low hemoglobin, I try to give voxelotor.”
Dr. Goldstein says he has most often prescribed L-glutamine as a second drug.
Although crizanlizumab is more effective in preventing pain crises, both doctors are more likely to prescribe one of the two oral drugs first because they are more convenient. Because crizanlizumab is given by infusion, it requires a monthly office visit.
Some people taking either of the two oral drugs have side effects, primarily those affecting the digestive tract such as nausea, abdominal pain, diarrhea or constipation. Voxelotor may cause a rash for some people. Crizanlizumab sometimes will cause a reaction at the injection site.
As for the future, multiple new drugs and gene therapies are in the development stages.
Advances in drug treatment are helping to improve results for patients, but taking care of sickle cell patients remains a team effort, Dr. Varadi notes.
“You need a primary care doctor, you need the hematologist and the pain management doctor who follow you, and sometimes you need blood transfusions. So it’s a very complicated effort, but together we can do it.”