Changing Therapies for Sickle Cell Disease

Sickle cell disease (SCD) has been studied for more than a century. In 1949, scientist Linus Pauling showed that it was a molecular disease. Yet for decades, treatment options barely moved forward. Until recently, the main option beyond supportive care was a bone marrow transplant. That has now changed. In the last six years, we’ve seen more progress than ever before.

Who is affected

SCD is the most common inherited blood disorder, affecting more than 30 million people worldwide. It is most common in areas such as sub-Saharan Africa, the Mediterranean, India, and the Caribbean. In the United States, about 100,000 people live with SCD. More than 95% are of African ancestry. The numbers are striking:

• 1 in 365 African Americans are born with SCD.

• 1 in 16,300 Latinx babies are born with SCD.

• About 1 in 13 African Americans carry the sickle cell trait.

SCD likely evolved in areas with high rates of malaria because carrying the sickle cell trait offers some protection against malaria.

Living with the disease

As a physician who also lives with SCD, I wrote a book to explain the condition to the medical community. It’s titled ALL RISE: The Sickle Cell Community vs. the Medical Establishment. In it, I cover the science, the patient experience, and the treatments now available.

There are several different genetic types (genotypes) of SCD, including SS, SC, S-Thal zero, and S-Thal plus. Each presents differently, which is why a variety of treatments are needed.

Early treatments

Bone marrow transplant was long seen as the only potential cure. But it requires a perfectly matched sibling donor, which most patients don’t have.

In 1998, Hydroxyurea (Hydrea) was introduced. Originally used to treat certain cancers, it was found to boost fetal hemoglobin levels. This matters because fetal hemoglobin doesn’t carry the sickle mutation. Higher levels of fetal hemoglobin can mean fewer complications. Some patients saw real benefits, but others didn’t respond well or couldn’t tolerate the side effects.

Newer therapies

After decades of waiting, the first drug designed specifically for SCD was approved in 2017: Endari. Made from L-glutamine, it helps red blood cells handle oxidative stress, making them less likely to sickle.

In 2019, two more treatments arrived within the same week:

• Oxbryta (pills) helped keep red blood cells oxygenated, reducing anemia and the need for blood transfusions.

• Adakveo (monthly infusion) blocked proteins that make cells stick together, lowering the number of painful crises and hospital visits.

Together with Endari, this gave patients three new options. Although Oxbryta was recalled in 2024, the progress was still groundbreaking.

The promise of gene therapy

The most exciting development has been gene therapy. In December 2023, the FDA approved Casgevy, developed by Vertex Pharmaceuticals. It uses CRISPR gene-editing technology to switch fetal hemoglobin production back on. This allows red blood cells to stay round and flexible instead of sickling.

Another company, Bluebird Bio, created Lyfgenia, which uses a viral vector to insert new genetic instructions into a patient’s stem cells. Both treatments aim for the same result: healthier blood cells and fewer complications.

Gene therapy is promising because it uses a patient’s own cells, eliminating the need for a sibling donor. It is currently extremely expensive and not widely available, but it is the first real alternative cure since bone marrow transplant.

Looking ahead

After decades of slow progress, the last six years have brought remarkable change. From Hydroxyurea to Endari, Adakveo, and now gene therapy, patients have more options than ever.

As both a doctor and a patient, I celebrate these steps forward. I remain hopeful that every person with SCD will soon have access to treatments that work for them. That would truly be a beautiful day.