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Text |Amino observations.December 8 is destined to be a day that will be recorded in the history of genes.
On the same day, the FDA officially approved the marketing of Casgevy, a gene-editing drug jointly developed by Futai Pharmaceutical and CRISPR Therapeutics.
This means that CRISPR gene editing** has been recognized by global pharmaceutical regulatory benchmarks, laying a solid foundation for its subsequent global promotion.
The launch of CASGEVY once again reflects the FDA's principle of leading the trend of innovative drugs and solving unmet clinical needs.
Clinically, although there is still controversy about the safety of CRISPR gene editing**, even so, the FDA still resisted the pressure to approve the market, once again sending a signal to encourage innovation.
On the same day, the FDA also sent another signal to the market. On the day of Casgevy's launch, Bluebird Bio's gene editing **Lyfgenia was also approved, and the indications overlapped with Casgevy.
The starting gun was fired for the race between two different genes, and the FDA's "conspiracy" is obvious: to encourage innovation, but also to encourage competition.
This is not a good thing for pharmaceutical companies. The FDA's encouragement of competition may mean that the first war is inevitable, and one side may "go public" or "lose momentum" due to performance gaps.
Casgevy and Lyfgenia were listed at the same time, and the brutal game had begun. Because of this, whether it is Bluebird Bio or CRISPR Therapeutics, they have staged a "batch = collapsed"**:
The former's share price is **40%, and the latter's share price is also down nearly 10%.
Compared with the historic moment of gene editing, the FDA's "conspiracy" may be what more pharmaceutical companies need to pay attention to.
The reason why Casgevy attracts the attention of the market is that it is a new era of gene editing.
Ten years ago, the birth of the CRISPR-Cas system allowed gene editing to enter the era of intelligent machines from straight board machines. Compared with the previous ZFN and Talens gene editing technologies, the CRISPR-Cas system has three significant advantages: simple operation, high accuracy, and low cost.
Since its launch, this technology has been implemented in countless biological laboratories around the world, and has great potential in the medical field.
There are more than 7,000 rare diseases worldwide, affecting more than 300 million people, 80% of which are caused by single gene mutations. At present, 95% of rare diseases still do not have effective ** drugs.
Using gene editing technology to modify mutated individual bases, such as cutting, adding or substituting, it is highly likely to save the lives of rare patients and restore their health.
Theoretically, any mutated gene can be corrected by the CRISPR-Cas system. And Casgevy is the first landing of this technology.
The core mechanism of Casgevy is to use CRISPR gene editing to engineer the patient's own hematopoietic stem cells, so that the cells can produce high levels of fetal hemoglobin.
Normally, fetal hemoglobin is only produced during fetal development, and its expression pathway is turned off after birth. However, some special cases have shown that some adults can also produce fetal hemoglobin when the BCL11A gene is mutated.
What Casgevy does is mimic this mutation, cleaving the Bcl11A of the patient's hematopoietic stem cells and loosening the brakes on fetal hemoglobin. This also makes casgevy have the potential for sickle cell disease.
Sickle cell disease is an inherited blood disorder in which a genetic mutation causes red blood cells to form a "sickle" shape. These cells can restrict the delivery of oxygen to the body and block blood flow, leading to severe pain or a crisis of vascular occlusion.
Currently, a total of 45 patients have received casgevy** in clinical trials for sickle cell disease. Data from 29 of these patients showed that 28 patients showed no signs of severe pain for at least 12 months after **.
Based on the dazzling clinical data, on November 16, 2023, the UK officially approved the marketing application of Casgevy, a gene-editing drug jointly developed by Futai Pharmaceutical and CRISPR Therapeutics. As a result, Casgevy became the world's first marketed CRISPR gene editing**.
Now, CASGEVY has been recognized by the FDA, which means that a new era of gene magic scissors has officially begun.
Compared to Casgevy, Lyfgenia is a completely different way of solving the problem.
Fundamentally, sickle cell disease is caused by a mutation in the globin gene. Human hemoglobin is composed of two strands and two strands, and the four strands are wound to form the spatial conformation of hemoglobin.
When the patient's amino acid in the sixth position of the peptide chain is released, the phenomenon of glutamic acid being replaced by valine will occur, and the sickle-shaped hemoglobin HBS will be formed, while the normal hemoglobin HBA will be replaced, which will eventually cause serious problems.
The idea of lyfgenia is to add a copy of the function of a modified form of the -globin gene (A-T87Q globin gene) to the patient's own hematopoietic stem cells.
Once a patient has the gene for A-T87Q globin, their red blood cells can produce hemoglobin that resists the sickling of red blood cells, thus reducing the proportion of sickle hemoglobin.
Judging from the clinical data, Lyfgenia has also shown great combat effectiveness.
In a single-arm study, Lyfgenia helped 28 of 32 patients (88%) to experience no signs of severe pain at all for 6 to 18 months after **.
At the upcoming American Society of Hematology Annual Meeting, researchers will present new data showing that 30 of the 33 patients who received lyfgenia** (90.)9%) had complete resolution of severe pain signs during this period, and 32 (97%) had no severe pain signs.
It was on the basis of outstanding performance that Lyfgenia received FDA approval. For Bluebird Bio, Lyfgenia is also the third time that its ex vivo gene** has been approved by the FDA, which is a glorious continuation.
It's just that, whether it's lyfgenia or casgevy, it is inevitable that there will be a sigh of "both Yu and Liang".
Although the clinical data of the above two genes** are excellent enough, they are only single-arm studies, so they are not enough to prove to the market who is better.
Prior to FDA approval, a new survey of 33 U.S. physicians conducted by Leerink Partners showed that more than 60% of hematologists in SCD believe there are no major differences in safety and efficacy between the two genes.
When asked which listing gene they would use**, 40% could not decide, while 1 in 3 chose lyfgenia.
This also means that on the first day of listing, the game of the two ** has begun.
For Casgevy, the disadvantages cannot be ignored.
First, there is the potential for security. If CRISPR gene editing technology cleaves a DN** segment other than the intended target, it may disrupt the function or regulation of the non-targeted gene, leading to serious consequences.
To determine whether Casgevy's off-target analysis is reliable, the FDA recently convened a think tank to vote. Although at the meeting, the expert panel affirmed the safety of the drug, it still needs to be proved by clinical data from pharmaceutical companies in a longer period of time.
Secondly, it is not advantageous at the commercial level. Gene editing is extremely cumbersome. For example, Casgevy first needs to remove stem cells from a patient's bone marrow and edit the cells in the lab and then infuse them back. Prior to reinfusion, the original natural hematopoietic stem cells in the bone marrow are eliminated to reduce the expression of subsequent abnormal hemoglobin and to allow room for the growth of new hematopoietic stem cells. After the infusion, the patient may need to be observed in the hospital for at least a month to avoid problems such as potential infection.
Therefore, for Casgevy, there is a need to accelerate the education of the physician community in the subsequent commercialization process. Although Lyfgenia's ** is also cumbersome, because Bluebird Bio has similar drugs on the market before, it has mature sales channels, and the volume may be more advantageous.
Because of this, Casgevy finally hit a low-price strategy: $2.2 million a shot, while Lyfgenia's ** reached $3.1 million.
Of course, for Lyfgenia, there are also security bugs that are visible to the naked eye. Clinical trials in Lyfgenia previously reported cases of acute myeloid leukemia that emerged after **.
In contrast to Casgevy's potential concerns, the issue of Lyfgenia's potential carcinogenesis was clear, so the FDA gave it a black box warning. In the absence of a black box warning from Casgevy, the promotion of Lyfgenia will be extremely passive.
So, even with the final pricing, Bluebird Bio's share price fell by more than 40%.
The purpose of pharmaceuticals is to serve patients. As a result, the FDA tends to be extremely inclusive when it comes to encouraging innovation. But at the same time of inclusiveness, the FDA also reflects its wise side: the introduction of "catfish" allows pharmaceutical companies to take the initiative to roll in.
This is not good news for pharmaceutical companies. From the competition of gene **, we can also further feel that technological innovation is only a means, and the highest mission of innovative pharmaceutical companies is to select suitable patients and suitable indications to ensure the effectiveness and safety of drugs. This is also the real foundation of pharmaceutical companies.