The groundbreaking CRISPR gene editing technology faced a pivotal moment as it underwent rigorous evaluation by the U.S. Food and Drug Administration (FDA). After a grueling seven-hour hearing, the FDA appears closer to granting approval for a revolutionary treatment known as “exa-cel.”
The Pioneers Behind the Innovation
Vertex Pharmaceuticals, headquartered in Boston, and Swiss-based CRISPR Therapeutics jointly submitted an application for a therapy that focuses on editing the genome to combat a devastating blood disorder: sickle cell anemia. This genetic anomaly is responsible for the deformation of red blood cells, causing them to take on the shape of a crescent moon, resulting in blockages in blood vessels and excruciating pain.
It’s one of the most common genetic disorders worldwide, affecting millions, with 100,000 cases in the United States. Additionally, this therapy holds the promise of improving the prospects for patients with another congenital anemia: beta-thalassemia, which necessitates lifelong blood transfusions.
The Agony of Sickle Cell Anemia
Sickle cell anemia transforms the normal, round shape of red blood cells into a crescent shape, leading to blockages in blood vessels and intolerable pain, severely hindering the possibility of a normal life. Regrettably, most patients do not survive beyond their 40s or 50s.
FDA’s Focus: Precision in Genetic Editing
During the FDA hearing, external experts shifted their focus from the efficacy and safety of exa-cel to the potential risks associated with the methods employed by Vertex and CRISPR Therapeutics. These methods proved successful in 29 out of 30 treated patients. However, concerns revolved around the possibility of unwanted changes in DNA, a phenomenon known as “off-target editing.”
These genetic modifications can be inconsequential or harmful, particularly if they affect specific regions of the genome. Tuesday’s meeting made it clear that the top priority for the U.S. regulatory body is to ensure that the treatment does not yield any unintended consequences.
Balancing Risk and Reward
By the end of the day, experts concurred on the need for further investigations. Several expressed their enthusiasm and firm belief that the benefits of exa-cel far outweigh any doubts regarding potential risks. Vertex’s officials plan to monitor treated patients for the next 15 years to identify any possible side effects.
The Unspoken Challenge: The Cost
What remained unaddressed during the FDA meeting is one of the primary challenges concerning exa-cel: its cost. With an anticipated price tag in the millions of dollars, its administration in less-developed countries, where the disease is more prevalent, is expected to be extremely challenging. Hepatologist Karl Kassamon rightly explained, “It’s a condition that disproportionately affects individuals of African, Southeast Asian, and Mediterranean [Middle Eastern] descent.”
The Path Ahead
This Tuesday’s proceedings usually signify the final step before the FDA makes its decision. The FDA’s deadline for this decision is set for December 8th.
Stories of Unimaginable Suffering
During the presentation, a group of patients who had already benefitted from preliminary clinical trials shared their harrowing experiences, with a heartfelt plea for the FDA to give the green light to exa-cel (certainly easier to pronounce than its full name: “exagamglogene autotemcel”).
From Pain to Hope: Transformative Outcomes
Victoria Gray, an African American woman, was the first to undergo the treatment. She revealed her harrowing experience, sharing that she had resorted to using “three different opioids” to manage her pain. At the peak of her struggles, she endured “three sleepless days” when she couldn’t use her legs or arms, let alone wield a fork to feed herself or wash her face.
Now, thanks to exa-cel, which she received in an experimental trial in Nashville, she can work full-time, “contribute to her family’s financial well-being,” dedicate herself to her children, and leave behind “blood transfusions, opioids, and frequent hospitalizations.”
Another witness, Kelly Howard, also of African American descent, recalled that she had been hospitalized “more than 13 times” before her first birthday, and in 2022, her hospital visits had soared to 100. She passionately added, “The treatment I implore you to approve for all sickle cell warriors has freed me from a disease I have fought for 33 years.”
The Remarkable Science Behind the Transformation
What the doctors did for Gray and Howard was to extract blood stem cells from their bone marrow, send them to a laboratory for editing using the CRISPR-Cas9 technique. Specifically, a gene called BCL11A, which regulates the production of fetal hemoglobin responsible for congenital anemia, was removed from the DNA.
The edited cells were frozen and subsequently transfused back into the patient after undergoing chemotherapy to eliminate the patient’s diseased blood cells in the bone marrow. Within a few weeks, the blood had regenerated itself, resulting in a healthier state.
A Global Impact
Once exa-cel receives definitive approval in the United States, it is expected that Europe will follow suit.
In 2012, Jennifer Doudna and Emmanuelle Charpentier developed a highly precise genome editing method, dubbed CRISPR-Cas9. This groundbreaking discovery, often likened to sophisticated genetic scissors, earned them the Nobel Prize in Chemistry in 2020. The Swedish Academy celebrated the potential of CRISPR for developing new therapies for various conditions, including cancer and hereditary diseases like sickle cell anemia and beta-thalassemia.
A World of Possibilities
The agri-food industry eagerly anticipates the myriad possibilities that this innovative technique has opened up.
In conclusion, the FDA’s evaluation of exa-cel is a significant step towards revolutionizing the treatment of sickle cell anemia and other genetic disorders. The potential benefits are immense, but challenges, especially regarding the cost, remain. The experiences of patients like Victoria Gray and Kelly Howard emphasize the transformational power of this therapy, offering hope to those who have suffered for far too long.
Original source: This information was Initially covered by Elpais and has been translated for our readers.