This is a milestone event in the history of gene editing treatments, approximately ten years after the birth of CRISPR gene editing technology, and represents a major scientific advancement that can benefit tens of thousands of patients. On December 8, local time, the U.S. Food and Drug Administration (FDA) approved the country’s first gene-editing treatment drug, Casgevy. This is also a milestone in the history of gene-editing treatment. It is about ten years after the birth of CRISPR gene-editing technology. It represents a major scientific progress that can benefit tens of thousands of patients.
Casgevy is being developed by pharmaceutical company Vertex Pharmaceuticals and biotech company CRISPR Therapeutics to treat sickle cell disease in adults 12 years and older. CRISPR Therapeutics, founded by Nobel laureate Emmanuelle Charpentier, won approval from UK regulators last month.
Sickle cell disease is an inherited blood disease in which a genetic mutation causes normally full-moon-shaped red blood cells to become half-moons that become lodged in blood vessels, restricting blood flow and causing bouts of severe pain.
"Sickle cell disease is a rare, debilitating and life-threatening blood disorder with an unmet need, and we are excited to advance the field, especially for individuals whose lives have been significantly disrupted by the disease," the FDA's Office of Therapeutic Products in the Center for Biologics Evaluation and Research said in a statement.
But the drug is also very expensive, with treatment costs as high as $2.2 million per patient. Based on Vertex's current drug manufacturing capabilities, approximately 16,000 patients with severe sickle cell disease will be eligible to receive the drug.
Although this gene-editing treatment only needs to be administered once, the entire preparation process takes several months. Specifically, the patient's blood stem cells first need to be extracted and isolated, and sent to the Vertex laboratory for genetic modification. But after the gene is edited, the patient needs several days of chemotherapy to remove old cells and make room for new ones. After the new cells are injected, the recipient spends several weeks recovering in the hospital.
Vertex CEO Reshma Kewalramani said: "We believe that the price of a drug can reflect the value it brings, and this value brings a one-time treatment that may cure a disease for a lifetime."
At the same time, a gene therapy Lyfgenia from Bluebird Bio was also approved by the US FDA on the same day for the treatment of sickle cell disease in people aged 12 and above. The cost of treatment per patient is as high as US$3.1 million.
In 2012, two female scientists, Jennifer Doudna and Emmanuelle Charpentier, published a groundbreaking paper on a gene editing system called CRISPR-Cas9, for which they subsequently won the Nobel Prize.
This discovery has led to numerous companies seeking to use CRISPR gene editing technology to treat various diseases, with sickle cell disease becoming a major target. Editing a patient's gene through CRISPR technology can activate so-called "fetal hemoglobin" to help red blood cells maintain a healthy shape.
In China, researchers are also aiming to use CRISPR technology to develop drugs to treat genetic diseases including thalassemia and sickle cell disease. A reporter from China Business News combed through public information and found that there are currently many domestic biotechnology companies such as Boya Jiyin, Biyao Biotech, Bendao Gene, Ruifeng Biotech, and Zhongyin Technology, which are engaged in the development of gene editing therapy products, and many products have entered the clinical trial stage. Among them, transfusion-dependent β-thalassemia is a popular target; in addition, retinitis pigmentosa caused by genetic mutations is also a direction. Taking transfusion-dependent beta-thalassemia as an example, the number of moderate to severe patients in China reaches 300,000.
However, the development of gene-editing drugs also faces ethical risks. In fact, as early as April 2015, Professor Huang Jun of Sun Yat-sen University published the world's first research results using CRISPR/cas9 gene editing technology to modify the thalassemia-causing gene in human embryos. However, he was accused of challenging ethical boundaries.
In this regard, Professor Ge Junbo, an academician of the Chinese Academy of Sciences and director of the Department of Cardiology at Zhongshan Hospital Affiliated to Fudan University, said: "I think medicine can have crazy ideas, but crazy behaviors should be rejected."
In addition, domestic companies still have room for improvement in gene editing therapy technology. Gene editing technology is difficult. The previous methods of imitating molecular structural formulas and bypassing compound patents have failed, and more original thinking is required.
In terms of safety, compared with in vitro gene editing, which can control the edited products entering the human body through quality control, in vivo gene editing cannot carry out similar quality control. If an off-target event occurs, incorrectly edited cells will still remain in the body.
In terms of payment, gene editing therapies are expensive and face certain challenges in China. Ding Sheng, founding dean of the School of Pharmacy at Tsinghua University, pointed out in a previous interview that compared with ordinary drugs, the early research and development of gene therapy methods has a high threshold. The design, optimization and even carrier selection of therapeutic genes are not easy, and the chain of gene therapy is very long. Which carrier to choose, which fragment of therapeutic gene, and which technology to use in the gene therapy process. Each link needs to be designed and quality-checked according to the patient's situation to ensure safety. This makes it difficult to mass-produce some types of drugs and the production cost remains high.