Key Points:
- The FDA has approved two gene therapies for sickle cell disease.
- The treatments use a patient’s own stem cells to prevent red blood cells from sickling.
- The therapies have shown promising results, but come with risks and are expensive.
The U.S. Food and Drug Administration has just approved two milestone treatments that promise a cure for sickle cell disease in patients 12 years and older.
Sickle cell disease is a group of inherited blood disorders and affects about 100,000 people in the U.S., most of them African American. The disease occurs, but is less prevalent, in Hispanics.
The treatments are named Casgevy and Lyfgenia and represent the first cell-based gene therapies for sickle cell disease. Additionally, one of these therapies, Casgevy, is the first FDA-approved treatment to utilize a type of novel genome editing technology.
The primary problem in sickle cell disease is caused by a mutation in hemoglobin, the protein that delivers oxygen to the body’s tissues. It causes red blood cells to develop a crescent or sickle shape instead of the normal disc shape. The mutated cells restrict the flow of blood in vessels and limit the amount of oxygen making it to tissues, causing severe pain and organ damage. The recurrence of crises can lead to life-threatening disabilities and early death.
The gene-based therapies use a patient’s own stem cells which are genetically modified to prevent red blood cells from developing the sickle shape. The modified stem cells are given back as a one-time, single-dose infusion.
The process is extremely expensive and not without considerable risk.
Prior to the re-introduction, the patient undergoes a heavy chemotherapy to remove cells from the bone marrow so they can be replaced. The entire process takes up to 18 months and patients must be monitored for the rest of their lives for complications that may arise years after treatment.
For patients in the clinic trials ahead of the FDA approval, the success rate was impressive. Patients all had a history of at least two crisis episodes during each of the two years prior to screening. The primary outcome was freedom from crisis for at least 12 consecutive months in the 24-month follow-up period.
A total of 44 patients were treated with Casgevy. Of those 31 had sufficient follow-up time to be evaluated and 29 of those achieved the desired outcome. No patients had graft failure or rejection.
The most common side effects were low levels of platelets and white blood cells, mouth sores, nausea, musculoskeletal pain, abdominal pain, vomiting, fever and low white blood cell count, headache and itching.
The safety and effectiveness of Lyfgenia is based on a 24-month multicenter study in patients between 12 and 50 with sickle cell disease. Effectiveness was evaluated based on complete resolution of crisis episodes between 6 and 18 months after infusion with Lyfgenia. Twenty-eight (88%) of 32 patients achieved the desired results.
The most common side effects included stomatitis (mouth sores of the lips, mouth, and throat), low levels of platelets, white blood cells, and red blood cells, and febrile neutropenia (fever and low white blood cell count), consistent with chemotherapy and underlying disease.
Blood cancer has occurred in patients treated with Lyfgenia. A black box warning is included in the label for Lyfgenia with information regarding this risk. Patients receiving this product should have lifelong monitoring for these malignancies.
