The revolutionary CRISPR gene editing was presented this Tuesday to the demanding examination of the US Drug Agency (FDA). After a seven-hour hearing, the health regulator seemed closer to approving a treatment based on this technique and named exa-cel.
The permission was requested by the laboratories Vertex Pharmaceuticals, based in Boston, and the Swiss CRISPR Therapeutics, whose stock trading was suspended for the duration of the session. Together they have designed a therapy based on genome editing against a painful blood disease: sickle cell anemia, a genetic malformation responsible for the deformation of red blood cells. It is one of the most frequent in the world, and affects millions of people, 100,000 in the United States alone. It also promises to improve the outlook for patients with another congenital anemia: beta-thalassemia, which requires lifelong transfusions.
Sickle cell anemia causes red blood cells, instead of the usual round shape, to acquire the silhouette of a half-moon, which causes them to get stuck in the blood vessels and cause pain incompatible with the development of a normal life. Most patients do not live beyond 40 or 50 years.
The outside experts convened by the FDA devoted the hearing not so much to the effectiveness or safety of exa-cel, but to whether the methods used by Vertex and CRISPR Therapeutics, which were shown to be successful in 29 of the 30 patients treated, have the potential risk of making unwanted changes to DNA. This is what is known as “off-target editing”: genetic modifications that can be inconsequential or be harmful if they affect certain regions of the genome. As became clear this Tuesday, it is a priority for the US health regulator to guarantee that the treatment will not have these unintended effects.
At the end of the day, the experts agreed on the usefulness of further testing, but several of them expressed enthusiasm, as well as the belief that the benefits of exa-cel far outweigh any doubts about its risks. Those responsible for Vertex plan to follow up the treated patients over the next 15 years to identify possible side effects.
What was not discussed at the FDA meeting is one of the main obstacles to exa-cel: its price. It is expected to cost millions of dollars, making it almost impossible to administer in less developed countries, where the incidence of the disease is highest. “It is an ailment that affects people of African, Southeast Asian and Mediterranean descent. [por Oriente Próximo]”explained hepatologist Karl Kassamon.
This Tuesday’s process usually represents the final step before the agency makes a decision. The FDA has a deadline of December 8.
stories of pain
During the presentation, a dozen patients who have already benefited from preliminary clinical trials shared their cases, with the request that the fda gives light green to exa-cel (certainly easier to say than its full name: “exagamglogene autotemcel”).
They described unimaginable sufferings. Perhaps the most famous case is that of Victoria Gray, a black woman who was the first to undergo the treatment and opened the public hearing this Tuesday to say that she consumed “three different opiates” to treat her pain and that During the worst crisis of her life, she stayed awake for “three days.” She “couldn’t use her legs or arms; she couldn’t even hold a fork to feed me, nor wash my face.” Now, thanks to the exa-cel, which he received in an experimental trial in Nashville, he can work full time, “contribute to the family economy” and dedicate himself “to his children,” and he has left behind “blood transfusions, opiates and the constant hospitalizations.”
Another witness, Kelly Howard – also African American – recalled that before she was one year old she was hospitalized “more than 13 times” and that in 2022 the visits rose to 100. “The treatment that I ask you to approve for all anemia warriors sickle cell has freed me from a disease that I have fought against for 33 years of my life,” he added.
What the doctors did with Gray and Howard was extract blood stem cells from their bone marrow, and send them to a laboratory where they were edited using the CRISPR-Cas9 technique. From the DNA, they cut a gene called BCL11A which controls the production of a protein, fetal hemoglobin, responsible for congenital anemia. The edited cells were frozen and sent back to the hospital, where, after a chemotherapy treatment to kill diseased blood cells in the marrow, they were transfused back into the patient. In a few weeks, the blood, regenerated by itself, was thus clean.
Once the exa-cel is definitively approved in the United States, Europe is expected to follow the same path.
In 2012, Jennifer Doudna and Emmanuelle Charpentier developed a method for high-precision genome editing that they named CRISPR-Cas9. That discovery, something like a very sophisticated pair of genetic scissors, earned them the Nobel Prize in Chemistry in 2020. The Swedish Academy then highlighted the possibilities of CRISPR to develop new therapies against cancer or many other hereditary diseases, such as sickle cell anemia. or beta-thalassemia.
The agri-food industry is also rubbing its hands at the world of possibilities that this new technique has opened up.
You can follow SUBJECT in Facebook, x and instagramor sign up here to receive our weekly newsletter.
#drug #agency #opens #door #treatment #CRISPR #gene #editing