NEW ORLEANS, La.—Sickle cell disease (SCD) affects some 100,000 Americans, causing chronic background pain as well as acute, crippling agony that has driven many patients to hospital emergency rooms, desperate for relief.

Yet because that pain cannot be measured objectively and varies greatly from one patient to the next—and because the disease mostly affects Black people—it has historically been neglected.

In recent years, however, efforts to track SCD while developing effective treatments, including gene therapy, have gathered steam. Both were a major focus of discussion at the 64th ASH Annual Meeting and Exposition, which drew 30,000 hematologists, oncologists, researchers and others here.

The event was hosted by the American Society of Hematology (ASH), which in October 2020 received a $2 million grant from the US Department of Health and Human Services’ Office of Minority Health to establish a nationwide learning community that aims to improve the care and quality of life of people with SCD.

“When we began this process, data was very intimidating to a lot of our providers,” said Venée Tubman, MD, codirector of the Sickle Cell Disease and Thalassemia Program at Texas Children’s Hospital. “We also know that sickle cell disease has historically been neglected, and that our patients suffer from negative stigmas, so this is the right thing to do.”

Alexis Thompson, MD, MPH, chief of hematology at Children’s Hospital of Philadelphia in Pennsylvania, said the learning community is one of 3 components to the ASH Research Collaborative, established in 2018 to accelerate change in clinical research for SCD and multiple myeloma. The others are the Data Hub and SCD Clinical Trials Network, which consists of 20 consortia and clinical sites.

“Our goal is to improve patient outcomes nationwide; to increase adoption of evidence-based practices; to establish a network of providers who share best practices; to standardize care across SCD centers, and to develop a community of SCD providers,” Dr. Thompson explained.

“We capture real-time, real-world data to generate real-world evidence. Sources can be electronic health records, though it can be onboarded from other sources as well, such as case reports.”

So far, she said, 40 sites in 17 states have enrolled, ranging from Emory University in Atlanta, Georgia, to New Jersey’s Newark Beth Israel Medical Center. The records of nearly 12,000 patients have been submitted; this comprises 2.8 million observations, 3.9 million medication prescriptions, 1.5 million procedures, and 2 million encounters.

Experts: SCD Finally Emerging as a Medical Priority

An “active participant” in the project is defined as any patient with 1 or more encounters of any type during a given year. Some 50% of those participants are younger than 20 years old and 26% had an inpatient encounter in 2022, down from 34% in 2018.

These patients go to hospitals and clinics with an array of documented conditions, including hypertension (30.79%); acute kidney injury (12.79%); chronic kidney disease (12.73%); venous thromboembolism (12.07%); priapism (8.76%); and cerebrovascular accidents (3.83%).

Dr. Thompson said the establishment of an SCD learning community—basically a network of patients, families, clinicians, and researchers working together and using data to improve health outcomes—is absolutely essential given the historic neglect that patients with SCD have faced.

Indeed, when compared to other diseases, SCD has clearly not been a priority for the medical establishment. Cystic fibrosis, which is only a third as prevalent as SCD—yet affects mainly Caucasians—received an average $2807 in annual funding per patient from the National Institutes of Health between 2008 and 2018, compared to $812 per patient for SCD.

According to Dr. Thompson, only 22%-45% of children with SCD receive an annual transcranial Doppler exam—a standard noninvasive, painless ultrasound procedure that uses high-frequency sound waves to measure the rate and direction of blood flow inside vessels.

Furthermore, only 18% of young children with SCD receive at least 300 days of antibiotics per year, and just 16% of eligible children and 10% of adults have hydroxyurea prescription coverage for at least half the year.

“ASH already has a remarkable array of tools we think can be implemented for SCD including cerebrovascular disease, cardiopulmonary and kidney disease, transfusion support, stem cell transplantation, and management of acute and chronic pain,” she said.

“Today we’re more focused on getting more sites in, so we get as clear a picture as we can,” she added. “We have the opportunity to have over half the sickle cell disease patients in the United States in the hub. I’m thrilled what I can already do with 12,000 patients.”

Study: Gene Therapy for SCD Is Cost-Effective

Meanwhile, the race to cure SCD using one-off gene therapy has already begun. Bluebird Bio, one of several pharmaceutical companies with potential treatments in the pipeline, is likely to seek US Food and Drug Administration (FDA) approval for its lovotibeglogene autotemcel (LentiGlobin) gene therapy in early 2023 after several regulatory delays.

In addition, 2021 saw a 32% jump in the number of clinical trials for SCD, despite the COVID-19 pandemic.

“With ASH now focusing on and prioritizing sickle cell disease, we are really excited by the idea that perhaps this disease that’s been historically marginalized is finally getting the attention it needs and deserves,” said hematology professor George Goshua, MD, of the Yale University School of Medicine in New Haven, Connecticut.

In an interview, Dr. Goshua estimated that a gene therapy treatment for SCD would cost $2.7 million. That compares to just over $1 million for the current standard-of-care, making it not particularly cost-effective from a purely economic point of view.

But when adjusted for historic income inequality and racism among Black and Hispanic people—which are disproportionally affected by sickle cell disease—gene therapy definitely makes more sense, according to a cost analysis presented by Dr. Goshua at the ASH meeting.

“This is the first study that has mathematically modeled health inequities, in addition to the cost-effectiveness component in sickle cell disease,” he told Rare Disease Advisor. “Our patients with SCD really suffer from a lot of health consequences as they move through their life. Every year is an added risk for heart failure, kidney disease, and high blood pressure.”

Gene therapies already rank among the world’s most expensive medications. These include etranacogene dezaparvovec (Hemgenix) for hemophilia B ($3.5 million), beti-cel (Zynteglo®) for beta thalassemia ($2.8 million); and onasemnogene abeparvovec-xioi (Zolgensma®) for spinal muscular atrophy ($2.1 million).

“We can actually put down a value on how much would be a fair price from an equity standpoint,” Dr. Goshua said. “It depends on whether you’re a man or a woman when you receive gene therapy, but it seems that prices even as high as $3.5 million still are right on the outer edge of equitable solutions. This is assuming gene therapy is 100% effective.”