The U.S. Food and Drug Administration (FDA) has granted approval for two revolutionary gene therapies for the treatment of sickle cell disease. Notably, one of these therapies is the first-ever treatment in the United States to utilize the Nobel Prize-winning CRISPR gene editing technology. The approved therapies, Casgevy jointly developed by Vertex Pharmaceuticals and CRISPR Therapeutics, and Lyfgenia by bluebird bio, are intended for individuals aged 12 years and older.
CRISPR, uncovered by Jennifer Doudna and CRISPR Therapeutics co-founder Emmanuelle Charpentier, employs molecular "scissors" to precisely trim defective sections of genes. These sections can then be disabled or substituted with healthy strands of DNA. On the other hand, bluebird bio's gene therapy operates by introducing modified genes into the patient's body via disabled viruses.
Sickle cell disease is an inherited blood disorder that causes painful symptoms. It is characterized by the production of abnormal, sickle-shaped hemoglobin, which impairs the ability of red blood cells to adequately carry oxygen to the body's tissues. The disease can severely impact the lives of individuals and even lead to premature death. It predominantly affects Black individuals, with an estimated 100,000 people currently affected in the United States.
Peter Marks, director of the FDA's Center for Biologics Evaluation and Research, emphasized that the approval follows extensive evaluations of scientific and clinical data, as the FDA is committed to promoting the development of safe, effective treatments for conditions with significant health consequences.
Sickle cells have a tendency to adhere together, leading to blockages in small blood vessels and causing intense pain. They can also result in organ failure and strokes. In separate clinical trials, both approved treatments demonstrated positive outcomes, with 29 out of 31 Casgevy patients and 28 out of 32 Lyfgenia patients experiencing improvements and fewer painful episodes.
Shares of CRISPR Therapeutics rose by 1.6% in response to the approval announcement, while Vertex Pharmaceuticals' stock declined by 1.4%. Conversely, bluebird bio's shares experienced a significant drop of 20%. Vertex's stock has seen a steady increase of over 20% this year, while CRISPR's stock has surged by more than 70%.
Although the drugmakers have positioned these therapies as one-time treatments, limited data is available regarding the long-term effectiveness. Currently, a bone marrow transplant is the only longer-term treatment option for sickle cell disease. Standard care includes the use of hydroxyurea, a chemotherapy drug, and once-daily medications such as Pfizer's Oxbryta, which aims to slow down the breakdown of red blood cells.
In the case of Vertex's therapy, patients are required to undergo bone marrow stem cell collection. These cells are then sent to manufacturing facilities, where they are edited using CRISPR/Cas9 technology. Following incubation, the modified cells are infused back into the patient during a month-long hospital stay.
Treatment with these gene therapies can be a lengthy process, taking several months and involving high-dose chemotherapy, which may carry a risk of infertility. The FDA has issued a black box warning for Lyfgenia, cautioning patients about the potential risk of blood cancer. Hence, patients treated with this therapy should undergo lifelong monitoring for such cancers, as advised by regulatory authorities.
In previous documents, FDA staff had expressed concerns about unintended genomic alterations arising from Vertex's treatment. To address these concerns, the company plans to conduct a comprehensive 15-year follow-up study to assess potential long-term safety risks following approval.
Furthermore, Vertex's CRISPR therapy is also currently under FDA review for another blood disease called transfusion-dependent beta thalassemia. A decision on its approval for this condition is expected by March 30.