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◎Boyagein CEO Wei Dong said, “This is an exciting data that reflects the effectiveness of the therapy.” This is mainly due to the fact that Intellia is still using relatively low doses, which has been achieved. Efficacy. Intellia also stated that it will try higher doses in the future to make the data (average decrease in TTR) reach more than 90%. If this level can be sustained for long-term observation, it also indicates that in vivo gene editing therapy may also achieve a one-time cure.
Every time reporter Jin Zhe Every time editor Tang Hui
On June 27th, Intellia Therapeutics and Regeneron jointly announced that the in-development CRISPR in vivo genome editing therapy NTLA-2001 has achieved positive results in a phase 1 clinical trial: a single dose of NTLA-2001 leads to serum transthyretin The protein level (TTR) decreased by 87% on average, and the maximum decrease in TTR was 96% on the 28th day.
In this regard, Boya Jiyin CEO Wei Dong said in an interview with the reporter of “Daily Business News” that the release of Intellia Therapeutics’s clinical trial data means the success of the first clinical trial of in vivo gene editing therapy. The clinical trial data shows The high gene editing efficiency, safety and potential one-time cure possibility of gene editing therapies using the CRISPR/Cas system in the body are very good results in the industry.
The world’s first in vivo gene editing clinical trial results announced
It is understood that NTLA-2001 is an innovative therapy for gene editing in vivo. It uses lipid nanoparticles (LNP) to package a CRISPR gene editing system that targets the TTR gene.
The results of the study showed that the clinical trial data included 6 ATTR patients who were treated in the phase 1 clinical trial, of which 3 received NTLA-2001 at a dose of 0.1 mg/kg, and the other 3 received a dose of 0.3 mg /kg of NTLA-2001 treatment.
The test on the 28th day of treatment showed that NTLA-2001 can dose-dependently reduce the TTR level in the patient’s serum. The 0.1 mg/kg dose group TTR decreased by an average of 52%, and the 0.3 mg/kg dose group TTR decreased by an average of 87%. One patient’s TTR level decreased by 96%.
“This is an exciting data that reflects the effectiveness of the therapy.” Wei Dong pointed out in the interview that this is mainly due to the fact that Intellia is still using relatively low doses and has achieved such a curative effect. Intellia also said that it will try a higher dose in the future, making the figure more than 90%. If this level can be sustained for long-term observation, it also indicates that in vivo gene editing therapy may also achieve a one-time cure.
The results of the study also showed that in terms of safety, as of the 28th day after receiving treatment, NTLA-2001 showed good safety, and no serious adverse events and liver problems were found. All adverse events were mild adverse events (Grade 1).
“Although the current observation period is relatively short, the two potential risks of off-target effects and safety issues that have been worried in the industry have not appeared.” Wei Dong explained that one potential risk is because Cas 9 itself is a protein. Will cause an immune response, no related problems were observed in this test. The other is about whether gene editing will produce off-target effects and cause significant side effects.
He emphasized that the clinical trial did not observe obvious off-target effects or any clinically significant side effects related to gene editing.
Breakthrough: Gene editing technology can be transformed into safe therapy after rigorous development
The “Daily Business News” reporter noted that the above-mentioned research results were also published in the “New England Journal of Medicine”, and the global medical community is excited about it.
Dr. John Leonard, President and CEO of Intellia, said that this is the first clinical data in history to show that it is possible to precisely edit target cells in patients through a single intravenous infusion of the CRISPR system to treat genetic diseases. The potential to suspend and reverse ATTR in the case of a single dose. Solving the challenge of targeted delivery of the CRISPR/Cas9 system to the liver also opens the door to the use of our technology platform to treat a wide range of other genetic diseases.
“From a professional point of view, this is the data that the gene editing industry has been expecting for a long time, giving the entire field a lot of hope.” Wei Dong told reporters that he had previously used CRISPR Therapeutics to target blood transfusion-dependent thalassemia and sickle. Clinical trials of type anemia have proven that gene editing technology can bring one-time cures in in vitro gene editing. These data show the great potential of gene editing technology in one-time cure of diseases. “This is a subversion of existing treatments. Methods and standards”.
He cited, for example, for the disease studied by Intellia, there are currently approved RNAi therapies, but patients need to be treated every three weeks, and there are many potential side effects, and if the gene editing therapy turns out to be a one-time cure If so, it is a subversion for the existing treatment plan.
At the same time, Verve Therapeutics, which was listed on the US NASDAQ in the first two weeks, plans to base edit the PCSK9 gene to lower cholesterol levels. Wei Dong pointed out that if their therapy is finally proven to achieve a one-time cure, then the treatment of related fields will also be a subversion.
“Of course, this is a good starting point. After all, gene editing therapy is still in its infancy, and there is more work to be done to achieve more breakthroughs.” Wei Dong emphasized that first of all, whether it is gene editing in vivo or in vitro For therapies, what scientists currently do more is to interfere with or destroy a gene, and the real replacement or modification of genes still requires the application of more complicated technologies that seem to be more complicated at present. “We also expect to see more changes in this regard in the future.”
He also mentioned that the second point is that the liver is an organ that is relatively easy to edit through LNP (Liposome) or AAV delivery. For more complex organs such as the brain or heart, there is still a lot of work to be done on how to edit to achieve treatment while avoiding safety issues.
The third point is long-term safety and effectiveness. At present, both the clinical aspects of in vitro and in vivo gene editing therapy are recent successes. The effect of a one-time cure requires sufficient time of observation to be verified, and if there are some other off-target effects or potentially causing cancer problems, long-term observation is also required. This also shows that based on the current achievements of the gene editing system, long-term observations are needed to truly establish long-term safety data.
China’s basic research on gene editing technology is not inferior to developed countries
In recent years, the idea of treating diseases through gene editing technology has received widespread attention. Especially since 2020, CRISPR gene editing technology has shined, won the Nobel Prize in Chemistry, and made great progress in clinical aspects. However, for this unknown frontier technology field, no real therapy has been born in the world, and the process from technology to clinical transformation is still full of various challenges.
In China, there are not many drug development companies that dare to challenge this frontier field, and Boya Jiyin is one of them. Wei Dong once said publicly that entering the scientific field of gene editing therapy, which is full of innovation and unknown, is like jumping into the deep sea. But this time, we don’t want to wait to be pushed by the wave, but to really get ahead of the wave.
“China is not inferior to developed countries in terms of basic research on gene editing technology, and ranks second in the world in terms of related papers and patents.” Wei Dong mentioned that in terms of transformation, China has benefited from the dual-track clinical research system, that is, research. The clinical trials initiated by the author and the registered clinical trials approved by the National Food and Drug Administration are in parallel, and the advanced therapies brought by gene editing technology can accumulate data through medical technology clinical trials initiated by research institutions, and provide assistance to some patients.
However, in terms of clinical transformation, China still has some distance from the level of developed countries. Wei Dong mentioned that to truly transform the high-quality gene editing technology into therapies and finally to market to benefit the majority of patients, it is necessary to obtain clinical trial application approval from regulatory agencies and carry out registered clinical trials. With a number of formal clinical trials of phase I and phase II gene editing products in the United States and Europe, my country’s clinical transformation has been in an earlier stage of clinical trials initiated by researchers.
Public information shows that in 2018, the biopharmaceutical company CRISPR Therapeutics and the pharmaceutical company Vertex Pharmaceuticals obtained new drug research application approvals from the US and European regulatory agencies. This is also the world’s first new drug for in vitro CRISPR therapy initiated by a pharmaceutical company Clinical trials; In the same year, the US Food and Drug Administration (FDA) accepted the world’s first in-person CRISPR therapy New Drug Research Application (IND).
However, in my country, it was not until January 2021 that Boyar Group was approved by the State Food and Drug Administration for its clinical trial application (IND) for the gene editing therapy product ET-01 for transfusion-dependent β-thalassemia. The status of clinical trial application (IND) approval. In June of this year, ET-01’s phase I multi-center clinical trial information was publicized on the drug clinical trial registration and information disclosure platform (chinadrugtrials.org.cn), indicating that the trial is being launched.
Cover image source: Photograph.com