On December 8, 2023 the U.S. Food and Drug Administration (FDA) approved Casgevy and Lyfgenia, both cell-based gene therapies for the treatment of sickle cell disease in patients 12 and older. Further, Casgevy is the first approved treatment utilizing CRISPR, an innovative gene editing technology that was the basis of the research leading to the 2020 Nobel Prize in Chemistry.

Sickle Cell Disease

Sickle Cell Disease affects about 100,000 patients in the U.S., predominantly in the African-American community. A mutation in hemoglobin, the protein which carries oxygen in red blood cells, leads to a change in the red blood cell shape so the red blood cells resemble a sickle. Unfortunately, this sickle shape restricts the flow of red blood cells, limits oxygen delivery to tissues, causes pain, and results in organ damage called vaso-oclusive events (VOEs) or vaso-oclusive crises (VOCs).

Casgevy

Casgevy is approved for the treatment of sickle cell disease in patients with recurrent VOCs, attaining status as the first approved treatment leveraging CRISPR/Cas9 to edit the patients’ cells. During this process blood stem cells are removed from the patient, modified with CRISPR/Cas9, and returned to the patient using a one-time, single dose infusion. Prior to treatment, the patient’s blood stem cells are collected and the patient undergoes chemotherapy to remove stem cells from the bone marrow. The treatment then replaces the stem cells in the bone marrow with modified stem cells, allowing the patient to produce blood cells without the sickle trait.

During clinical studies, 44 patients were treated and 31 patients had enough time to be evaluated. 29 (93.5%) achieved the primary outcome of freedom from further VOC episodes.

Lyfgenia

Lyfgenia also modifies the patients’ cells but uses a lentiviral vector instead of the CRISPR technology. The process for treating the patient is similar to Casgey, as cells are removed from the patient and modified before being re-infused to the bone marrow. The modified blood stem cells produce HbA^T87Q, a gene-therapy derived hemoglobin which acts similar to hemoglobin A, the normal adult hemoglobin produced by cells not impacted by sickle cell disease.

Casgevy and Lyfgenia both received Priority Review, Orphan Drug, Fast Track and Regenerative Medicine Advanced Therapy designations. 

Implications

Gene and cell-based therapies are an exciting area of growth in the pharmaceutical space. With these approvals, new treatments will be available for patients suffering from sickle cell disease. Of particular note is that a CRISPR therapy is now available; the CRISPR/Cas9 gene editing technology is ubiquitous in the research and development world and the technology is now making an important step into the clinical realm as well.

Further, it’s exciting that CRISPR, a gene editing technique well suited to make single base pair changes in DNA, is now being harnessed to help patients suffering from diseases with point mutations. This approval opens the possibility of similar treatments in other diseases for patients desperately seeking assistance.

For more information, click here to read the full FDA press release.