All About the 2 Gene Therapies For Sickle Cell Disease

Advanced Science News

Sickle cell disease arises from a mutation in hemoglobin, a vital protein within red blood cells responsible for transporting oxygen throughout the body. Recently, two groundbreaking gene therapies, Casgevy and Lyfgenia, have received approval from the U.S. Food and Drug Administration (FDA) on December 8. This development presents a significant stride in addressing the painful inherited blood disorder, particularly prevalent among Black individuals.

These FDA-approved gene therapies hold the promise of not only alleviating symptoms but also potentially offering a cure for sickle cell disease. Casgevy and Lyfgenia operate by genetically modifying the stem cells of patients, ushering in a new era of treatment for individuals aged 12 and older. However, the advent of this medical breakthrough comes with a notable caveat—a considerable price tag accompanies these treatments. Additionally, the true extent of their long-term efficacy and potential side effects will only become evident after years of extensive usage and observation.

In essence, the approval of Casgevy and Lyfgenia marks a pivotal moment in the pursuit of a solution for sickle cell disease, opening avenues for improved quality of life and the possibility of a cure. Nonetheless, the financial implications and the need for comprehensive understanding of the therapies’ prolonged effects underscore the complexity and ongoing nature of medical advancements in this field.

“This is a monumental moment,” Markus Mapara, MD, PhD, said. He is a professor and the director of the blood and marrow transplantation program at Columbia University Irving Medical Center in New York City.

“It is too early to determine whether the new gene therapies will lead to sustained and long-term reversal of the symptoms of sickle cell disease,” Dr. Mapara said. He has worked as a consultant for companies that involved the two types of treatments. “But the current results look very promising.”

Sickle cell disease comprises a collection of uncommon disorders affecting approximately 100,000 individuals in the United States, with a majority belonging to the Black population, as per information from the FDA. The condition arises from a mutation in hemoglobin, a protein found in red blood cells responsible for transporting oxygen throughout the body. Due to this mutation, red blood cells assume a sickle shape, leading to the obstruction of blood vessels and restricting the oxygen supply to tissues and organs. This can result in severe pain, frequent hospitalizations, and premature mortality.


New Infusions for Sickle Cell Disease Came From Patients’ Own Cells

Various medications can address health issues linked to sickle cell disease, such as anemia, infections, stroke, and kidney damage, as highlighted by Mapara. While conventional treatment methods exist, including bone marrow transplants, which have been the sole curative option, recent advancements have introduced innovative approaches.

The traditional bone marrow transplant involves a complex process requiring chemotherapy to eliminate abnormal bone marrow responsible for producing defective, sickle-cell-shaped hemoglobin. Subsequently, healthy cells from a sibling are transplanted to replace the removed marrow. However, a new wave of treatments diverges from this model by harnessing a person’s existing stem cells.

Instead of relying on external donors, emerging treatments craft a unique infusion utilizing the patient’s own stem cells. Nonetheless, recipients still undergo high-dose chemotherapy before receiving these infusions.

Notably, Casgevy stands out as the inaugural drug approved in the United States utilizing the gene-editing tool CRISPR, according to the FDA. This groundbreaking medication functions by editing the DNA within a patient’s stem cells, removing the gene responsible for sickle-shaped red blood cells.

Contrastingly, Lyfgenia takes a distinct approach. It leverages a deactivated virus to transport a copy of a gene into the patient’s cells, enabling the production of healthy hemoglobin. This method provides an alternative avenue for addressing the genetic root of sickle cell disease, showcasing the diverse strategies emerging in the pursuit of effective treatments.

Clinical Trials for Casgevy and Lyfgenia Showed Promising Results

In a clinical trial assessing Casgevy’s efficacy, the FDA reported that 29 out of 31 patients with sickle cell disease remained free from vascular occlusive events—a condition linked to blocked blood vessels—for a minimum of one year following the infusion. Notably, the predominant adverse effects observed included diminished blood platelet and white blood cell levels, mouth sores, nausea, musculoskeletal pain, abdominal pain, vomiting, low white blood cell count-induced fever, headache, and itching.

Similarly, in the case of Lyfgenia, a clinical trial revealed that 28 patients with sickle cell disease achieved complete resolution of vascular occlusive events within a timeframe ranging from 6 to 18 months post-infusion, as per FDA findings. The primary side effects encompassed mouth sores, reduced platelets, white blood cells, and red blood cells, along with fevers associated with low white blood cell counts.

However, Lyfgenia comes with a black box warning, signifying the most severe side effects acknowledged by the FDA, particularly its potential to instigate blood cancers. Consequently, individuals undergoing this gene therapy necessitate lifelong monitoring for blood malignancies.

It is important to note that both gene therapies mandate a chemotherapy regimen beforehand, which may also lead to infertility as a potential side effect.

Cost and Access

The cost of treatment is substantial. Casgevy, developed collaboratively by Vertex Pharmaceuticals and CRISPR Therapeutics, is priced at $2.2 million, as reported by Reuters. Additionally, Bluebird Bio has set a $3.1 million price for its drug Lyfgenia, according to Reuters.

“We don’t know how much the out-of-pocket expenses will be,” Mapara said. “But the costs may be a barrier to access.”

Casgevy is currently authorized for administration in only nine treatment centers nationwide, according to Vertex’s statement. Lyfgenia, as mentioned by Bluebird Bio, can be administered in 27 treatment centers. Both companies express the expectation that more locations will be added over time.

Among the authorized treatment centers for both Casgevy and Lyfgenia, Boston Medical Center stands out as the sole location in New England. Despite potential initial limitations in accessibility due to factors such as costs, Jean-Antoine Ribeil, MD, PhD, the clinical director of the Center of Excellence in Sickle Cell Disease at Boston Medical Center, emphasizes the “monumental” significance of FDA approval for these new gene therapies.

“The new therapies leverage the latest advances in medical science to alleviate the devastating pain and long-term health impacts of sickle cell disease, bringing a long-awaited step toward equity in treatment to a disproportionally impacted Black patient population,” Dr. Ribeil said.