Pharmaceutical companies around the world have high hopes for atropine. After all, the demand for myopia prevention is very clear and huge. The most critical thing is the extremely large demand group. According to Eyenovia's estimates, myopia is estimated to affect about 25 million children in the United States, of which up to 5 million are considered to be at high risk of progressive myopia.

The same is true in China. According to Guosheng Securities' estimate, the size of the myopia group of children and young people aged 6-16 is about 78 million. For this group of people, there are currently two major problems: some groups have no effective means of delay, and those with means of delay need solutions with better compliance and lower costs. At present, among the main measures to control and delay myopia, wearing frame glasses is convenient but has poor effects; optical correction (wearing orthokeratology lenses) is limited to people over 8 years old, and there are certain requirements for myopia and astigmatism.

Surgical treatment is limited to people over 18 years old and is expensive. Therefore, the market needs a new product to make up for the pain points of the above solutions. Atropine has become a popular candidate. Since the 21st century, the research results of the Singapore Eye Research Institute's "preliminary effectiveness" have gradually attracted attention for the research on atropine in myopia control. Eyenovia has also joined the atropine research and development camp and has high hopes for its products. Eyenovia is exploring the mainstream 0.1% or 0.01% atropine dosage form, and the uniqueness lies in that it is paired with the company's Optejet based on its ocular medication technology platform. The advantage of Optejet is that it can bring better potential effects by improving the way of drug administration.

Eyenovia believes that if the product is successfully developed, the peak sales can reach more than US$1 billion. Unfortunately, in the study of the atropine series MicroPine, good luck did not favor Eyenovia. The results showed that there was no significant difference in the myopia progression rate between the two concentration groups of MicroPine and the placebo group. Eyenovia CEO Michael Rowe said that he was very sorry about this, but there was no way, the research and development of innovative drugs was so cruel.

Of course, it's not just Eyenovia. Atropine research in the United States has not been going well. In the middle of last year, an article published in the Journal of the American Medical Association Ophthalmology, "Low-Dose 0.01% Atropine Eye Drops vs Placebo for Myopia Control A Randomized Clinical Trial", made atropine a hot topic.

The study explored the effects of 0.01% atropine eye drops on school-age children with low and moderate myopia in the United States. The results of the study were not ideal. At baseline, the average spherical refraction (SER) changes in the atropine group and the placebo group were -2.83D and -2.83D, respectively, and -3.64D and -3.54D at 24 months. In other words, the vision of the atropine group declined faster. At the 30-month follow-up, the results were still the same. The mean spherical refraction (SER) changes from baseline were -0.94D and -0.88D in the atropine and placebo groups, respectively; the mean (standard deviation) changes in axial length from baseline were 0.51 mm in the atropine group and 0.49 mm in the placebo group. In other words, atropine 0.01% had no benefit at 24 and 30 months, and the results were consistent in different subgroups based on age, gender, race, and eye color.

In this regard, the researchers believe that there is no possibility that there is a problem with the trial. The core reason is that the trial is double-blind and placebo-controlled, the reported treatment compliance is very good, the loss rate at 24 months is the lowest (5%), and it has sufficient statistical power, so there is no reason to doubt that this result is due to bias or chance. This also forces researchers to think more, because according to their observations, the studies conducted in the East with atropine all look good. Indeed, in March this year, Xingqi Eye Drops' atropine sulfate SQ-729 was approved for marketing to delay the progression of myopia in children aged 6 to 12 with a spherical power of -1.00D to -4.00D (astigmatism ≤1.50D, anisometropia ≤1.50D).

According to the data presented by Xingqi Eye Drops, the registration study conducted with atropine sulfate SQ-729 injections, the primary efficacy indicator, the change in the equivalent spherical power of computer optometry after ciliary muscle paralysis at 48 weeks, and the secondary efficacy indicator, the change in the axial length at 48 weeks compared with the baseline, both reached the endpoint. In other words, atropine has the situation of "the east is bright when the west is not bright".

Why does this happen? The authors of the above study put forward several conjectures.

First, it is caused by different races. The researchers believe that a very likely reason is that there may be racial differences in the response to atropine eye drops. Myopia progresses faster in Asian groups, while myopia progresses slower in black children. Their study included black children, but fewer Asian children, which may lead to biased results. It seems that this situation may exist. After all, all the current studies pointing to the clinical benefits of atropine eye drops are from Asia.

Second, the product formula is different. In addition to the racial conjecture, the researchers also proposed another possibility, that is, the formula of atropine is different. Indeed, low-concentration atropine is not stable when the pH value is neutral. The current mainstream practice in the industry is to lower the pH value to maintain the stability of low-concentration atropine.

However, the result of too low pH value is that the patient's eyes will have an uncomfortable reaction, and tears will wash away the drug, which will eventually make it difficult for the drug to work. Therefore, it is necessary to adjust the pH value of atropine to neutral through patented technology, improve the absorption and efficacy of the drug, and reduce the patient's discomfort. From this perspective, the poor formulation of atropine will indeed lead to different clinical results. Of course, the above are just the researchers' conjectures, and the final result remains to be explored by the medical community. Perhaps American researchers also need to come to China to see.

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