Recent Gene Therapies for Sickle Cell Disease

Though we’re halfway through 2024, many people don’t know about the novel gene therapies recently approved by the FDA. CASGEVY and LYFGENIA have risen as a “functional cure” for many patients suffering from sickle cell disease. But before I delve into these therapies, what is sickle cell disease?

Sickle Cell Disease

Sickle cell disease refers to a group of disorders that are inheritable. In essence, an abnormal amount of hemoglobin causes red blood cells to stray from their regular disc-shape, becoming rather “sickle” or crescent-shaped. This mutation in shape causes sickled red blood cells to struggle in moving and leads to blocked blood flow. This can lead to complications such as pain, infection, and other serious complications like strokes. 

CASGEVY

The CASGEVY treatment works by utilizing the novel technology of CRISPR and has been made through the collaboration of Vertex Pharmaceuticals and CRISPR Therapeutics. CRISPR, adapted from the immune system of bacteria, allows for the most precise gene editing to date. Before treatments, patients receive a mobilization medicine to transport blood stem cells to their bloodstream. These cells are collected and are treated using CASGEVY, which makes precise edits on the patient’s stem cells to suppress the gene that stops the production of fetal hemoglobin. Patients, then, receive conditioning chemotherapy to get rid of existing stem cells in their bone marrow to leave space for treated cells. Upon infusion of the modified cells and successful engraftment, the patient is able to produce healthy, red blood cells. While the treatment has risks like unintended gene edits, the CASGEVY treatment showed 93.5% of candidates (29/31 candidates) didn't have severe vaso-occlusive crises for at least 12 consecutive months upon treatment. Further information about the clinical trial is disclosed on CASGEVY's website which also shows an interactive view of how the treatment works. CASGEVY is the first FDA approved treatment using CRISPR.

LYFGENIA

The LYFGENIA treatment is a cell-based gene therapy made by BlueBird Bio. This treatment uses a viral envelope to transport new genetic material. In essence, upon collection of the patient’s stem cells, copies of the beta-globin genes are added by a viral vector. The modified cells are infused back in the patient's body leading to a process known as engraftment, which causes production of healthy hemoglobin without sickling properties. Clinical trials have shown 88% of candidates (28/32) have not experienced vaso-occlusive events on 6-18 months of infusion while 94% of candidates (30/32) didn’t experience severe vaso-occlusive events. Though this treatment has been deeply studied according to BlueBird Bio, the treatment has a risk of blood cancer and slower recovery time for platelets. Further information is disclosed on the LYFGENIA website with a walkthrough of how the treatment works. 

Both of these treatments serve as innovative medical breakthroughs for patients 12 years and above suffering from sickle cell disease. While they are groundbreaking in nature, they have their risks with CASGEVY having the potential risk of unintended gene edits and LYFGENIA with the risk of blood cancer. Not to mention, both of these treatments require time and money to administer. Despite the significant hurdles, with few options to treat sickle cell disease, these treatments serve as milestone breakthroughs.

Citations

“Bluebird Bio Announces FDA Approval of LYFGENIATM (Lovotibeglogene Autotemcel) for Patients Ages 12 and Older with Sickle Cell Disease and a History of Vaso-Occlusive Events | Bluebird Bio, Inc.” Bluebird Bio, Inc., 2023, investor.bluebirdbio.com/news-releases/news-release-details/bluebird-bio-announces-fda-approval-lyfgeniatm-lovotibeglogene.

“CASGEVY (Exagamglogene Autotemcel) | Boston Children’s Hospital.” Www.childrenshospital.org, www.childrenshospital.org/treatments/casgevy#:~:text=CASGEVY%E2%84%A2%20(exagamglogene%20autotemcel)%20is. Accessed 15 July 2024.

CDC. “About Sickle Cell Disease.” Sickle Cell Disease (SCD), 6 May 2024, www.cdc.gov/sickle-cell/about/index.html.

FDA. “FDA Approves First Gene Therapies to Treat Patients with Sickle Cell Disease.” FDA, 8 Dec. 2023, www.fda.gov/news-events/press-announcements/fda-approves-first-gene-therapies-treat-patients-sickle-cell-disease.

“How Does LYFGENIATM (Lovotibeglogene Autotemcel) Work?” Www.lyfgenia.com, www.lyfgenia.com/what-is-lyfgenia/how-lyfgenia-works.

News, A. B. C. “FDA Approves Gene Therapies for Sickle Cell Disease, a “Functional Cure” for Many.” ABC News, abcnews.go.com/Health/fda-approves-new-gene-therapies-sickle-cell-disease/story?id=105482870.