Hengrui and Kangzhe entered the game! With 360 million patients, a glittering gold mine!

China is not only a big cancer country, but also a big country

Eye diseases are a common disease throughout the life cycle, from the infancy of 0-1 years old to the middle-aged and elderly people over 40 years old, from congenital cataracts to glaucoma, not only covering different age groups, the number of patients is huge, and the types of diseases are also quite extensive

Not only does it cover different age groups, the number of patients is huge, and the variety of diseases is quite extensive

Together, the two account for nearly 80% of the incidence of dry eye disease is 20-30%

Different from the treatment of myopia, which accounts for a relatively small proportion of drugs, drugs are currently the most mainstream treatment for

The huge patient population makes the dry eye drug market show good growth prospects

There is no doubt that the market pattern of dry eye drugs in China is undergoing major changes

360 million patients with dry eye, cyclosporine clinical recognition is high

360 million patients with dry eye, cyclosporine clinical recognition is high

Affected by various factors such as changes in the way of life of our people, the growth of the use time of electronic products, the increase in allergens, and the improper use of eyes, the current field of ophthalmology in China not only has a huge patient population, but also a wide range

At present, the field of ophthalmology in China not only has a huge patient population, but also a wide range

▲Ophthalmic disease patient flow Data source: public information, eggshell research institute collation

As far as dry eye is concerned

Among the 360 million patients with dry eye, water deficiency dry eye and lipid abnormality dry eye are the most common, and the patient population of the two reaches 180 million and 130 million, accounting for 50% and 36.

In a population of 360 million people with dry eye

By definition, dry eye syndrome (DED), also known as dry corneal serositis, refers to the instability of the tear membrane and ocular surface damage caused by abnormal tear fluid quality and quantity, or abnormal tear fluid dynamics, moderate to severe dry eye disease will be accompanied by obvious pain, resulting in a decline in the quality of life of patients, and even blindness

Moderate to severe dry eye can be accompanied by significant pain, leading to a decrease in the quality of life and even blindness

The prevalence is around 20%, but the treatment rate is only 10%, and there is a great unmet clinical need

The first stage of dry eye treatment is mainly physical therapy such as hot compresses and meibomian gland massage, and repair treatments such as artificial tear fluid (sodium hyaluronate eye drops), but it is mostly used to treat patients with mild symptoms, and it is impossible to fundamentally treat moderate to severe dry eye; The second stage is anti-inflammatory treatment mainly for patients with medium and high symptoms, and representative drugs include glucocorticoids, cyclosporine, and nonsteroidal anti-inflammatory drugs

The second stage is anti-inflammatory therapy, which is mainly aimed at patients with medium to high symptoms

At present, there are fewer choices for dry eye in China, mainly based on traditional artificial tears, which have limitations, and in the field of moderate and severe dry eye disease, which accounts for about 50% of patients and has a large market potential, China's treatment is still relatively single

At present, there are fewer choices for dry eye in China, mainly based on traditional artificial tears, which have limitations

In terms of anti-inflammatory treatment, China mainly uses glucocorticoid eye drops, but its side effects are large and cannot be used for a long time, and the most used abroad is a new generation of cyclosporine eye drops with better efficacy and less side effects, which is also the best-selling drug

The most used in foreign countries is the new generation of cyclosporine eye drops with better efficacy and fewer side effects

According to the 2018 American Academy of Ophthalmology Dry Eye Guideline Experiment, 0.
05% cyclosporine eye drops are effective for patients with mild, moderate and severe dry eye disease, with an effective rate of 74%, 72% and 67% respectively, which is the recommended treatment plan for mild, moderate and severe dry eye, and the only drug recommended in the guidelines except artificial tears; Artificial tear fluid is only recommended for mild dry eye.

It is also the only medication recommended in the guidelines except artificial tear fluid; Artificial tear fluid is only recommended for mild dry eye.

The golden track of 10 billion ophthalmic drugs, a new generation of dry eye drugs "jianghu"

The golden track of 10 billion ophthalmic drugs, a new generation of dry eye drugs "jianghu"

From the perspective of market prospects, because China's ophthalmology field has a huge patient population, and the prevalence rate is gradually increasing, the demand is rigid and strong, so it has a broad space
for development.

According to research data from Guosheng Securities, the size of the U.
S.
ophthalmic drug market in 2019 was 15 billion US dollars, while China's ophthalmic drug market was only 2.
8 billion US dollars (about 19.
3 billion yuan), which is a large gap
compared with the United States.
In addition, the number of eye disease patients in China far exceeds that of the United States, and the market potential is even greater
.
From 2015 to 2019, the compound growth rate of China's ophthalmic drug market size is 8%, and it is expected that the CAGR is expected to reach 17.
8% from 2019 to 2030, maintaining a rapid growth rate
.

China's ophthalmic drug market is only 2.
8 billion US dollars (about 19.
3 billion yuan)

Due to the limited limitations of highly dry eye disease in the treatment of artificial tear fluid, the new generation of dry eye drugs represented by cyclosporine occupy the mainstream of
the market.

The new generation of dry eye drugs represented by cyclosporine occupies the mainstream of
the market.

The first drug approved for the treatment of moderately severe dry eye disease was Cyclosporine Eye Drops Restasis, developed by Allergan in the United States, which was approved by the FDA in December 2002 for the treatment
of ocular inflammation associated with dry corneal conjunctivitis.

Cyclosporine eye drops Restasis developed by Allergan in the United States

Since its listing, Restasis has maintained a solid growth trend and has long dominated the market, reaching a peak sales of about US$1.
4 billion in 2016 and accounting for 47.
2% of
the global market share of dry eye drugs.

However, due to the use of castor oil as oil phase to dissolve cyclosporine in Restasis, there are defects such as slow onset of action (up to 6 months to start working), high frequency of medication and high burning sensation (stronger irritation to the patient's eye), resulting in poor
patient compliance.

This results in poor
patient compliance.

In addition, since 2017, restasis's sales have declined as Novartis' blockbuster ophthalmic drug, Lifitegrast eye drops Xiidra (originally developed by Shire and later acquired by Novartis for $5.
3 billion), and the listing of Sun Pharmaceutical's Cequa (0.
9% cyclosporine), have seen a decline
in sales.

Restasis' sales declined
.

Compared to Restasis's emulsion formulations, Cequa uses a nano-micelle formulation process, which has significant
advantages.

Due to the small particle size and large specific surface area of the micellar eye drops, it is easier to enter the eye through cell bypass, which is conducive to penetrating the physiological barrier system of the eye, and also increases the concentration of cyclosporine, and the onset rate is accelerated, thereby improving the bioavailability
of cyclosporine.
In August 2018, Cequa was approved for marketing by the FDA, becoming the first MICEL eye drop approved by the
FDA.

In August 2018, Cequa was approved for marketing by the FDA, becoming the first MICEL eye drop approved by the
FDA.

In May 2020, multinational pharmaceutical giant AbbVie completed its acquisition of Allergan for $63 billion and included Restasis
.
But at the same time, as Restasis's patents expire, generic drugs begin to go on the market, facing the threat
of a patent cliff.

But at the same time, as Restasis's patents expire, generic drugs begin to go on the market, facing the threat
of a patent cliff.

In February 2022, the FDA approved the listing of 0.
05%
of the cyclosporine ophthalmic emulsion of Mylan, The first generic drug of Restasis.
In addition, there are 9 pharmaceutical companies, including Teva Pharmaceutical, Pfizer and Akron, all of which are promoting the listing of Generic Drugs of Restasis, and the competition is quite fierce
.

 

The market pattern of dry eye drugs is about to usher in a huge change

The market pattern of dry eye drugs is about to usher in a huge change

In addition to overseas markets, the domestic market pattern of dry eye drugs is also about to undergo great changes
.

At present, in addition to Xingqi Eye Medicine, which has taken the lead in seizing the first-mover advantage in the market, there are many listed pharmaceutical companies such as Hengrui Pharmaceutical, Kangzhe Pharmaceutical, Kanghong Pharmaceutical, Hebo Pharmaceutical, Zhaoke Ophthalmology/Li's Pharmaceutical Factory
, etc.

According to the research report of Soochow Securities, although there is currently only one domestic Cyclosporine Eye Drops (Zirun ®) of Xingqi Eye Drug has been approved for listing, the overall research and development progress of the industry is relatively fast, and there are currently 6 drugs under study in the clinical phase III stage, of which 3 are cyclosporine for the treatment of dry eye, and 3 are other types of drugs, namely perfluorohexyl octane, ritast, and tenacept
.
In addition, there is a VVN001 eye drop in the clinical phase II
.

Although there is currently only one Xingqi eye drug in China, cyclosporine eye drops (Zirun ®) has been approved for marketing, and 6 drugs under research are in the clinical phase III stage

In June 2020, the 0.
05% cyclosporine eye drops (II) (Zirun ®), a dry eye treatment drug developed by Xingqi Eye Medicine, was approved for marketing by the State Food and Drug Administration for the reduction of tear production caused by ocular inflammation related to keratoconjunctival serosella, becoming the first and only approved eye preparation
for dry eye disease in China.

® It became the first and only approved eye preparation
for dry eye disease in China.

Although Zirun ® is a generic drug of Allergan's original research Restasis, the registration type is 3 categories (that is, drugs that imitate overseas marketed but not listed in China), but the product advantages and efficacy are more significant
.

® Allergan's original research on Restasis is a generic drug but the product advantages and efficacy are more significant
.

Zirun ® adopts a series of innovative processes such as Alic-Tech innovative technology and nano-scale microemulsion preparations, which not only realizes the leapfrog upgrading from ordinary emulsions to colorless transparent eye drops, but also has higher medication compliance and bioavailability, and reduces
adverse reactions.
According to phase III clinical studies, Zirun ® showed excellent efficacy and safety for moderate to severe dry eye and Sjögren syndrome-related dry eyes, with a total clinical effective rate of 70.
6%
at 3 months.

® Moreover, it has higher medication compliance and bioavailability, and there are fewer
adverse reactions.
®

In addition, due to the obvious first-mover advantage of Zirun ®, which can monopolize the market dividend, and successfully entered the national medical insurance directory through national negotiations at the end of 2021, the market penetration rate is expected to increase significantly, and the market prospects are promising
.

Due to the obvious first-mover advantage of Zirun ®, it can monopolize the market dividend ®

In addition to the research and development of generic drugs or improved new drugs, domestic pharmaceutical companies have also entered the market through License in or independent research and development strategies
.

In addition to the research and development of generic drugs or improved new drugs, domestic pharmaceutical companies have also entered the market through License in or independent research and development strategies
.

For example, Hebo Pharma's Tenacipra is a globally innovative drug imported from HanAll Biopharma and has the right
to develop, manufacture and commercialize in the Greater China region, including Hong Kong, Macau and Taiwan.
The drug, whose mechanism of action is to inhibit the tumor necrosis factor TNF-α, which causes inflammation of the eye, is currently in the clinical phase III stage and is expected to submit a BLA application
in 2022.

Hebopharm's Tenacipra is currently in phase III clinical phase III and is expected to submit a BLA application
in 2022.

In addition, Kangzhe Pharmaceutical's 0.
09% cyclosporine eye drops were introduced from Sun Pharma (Sun Pharmaceuticals), with the right to develop and commercialize in China, and the indication is to increase tear secretion
in patients with dry corneal conjunctivitis (dry eyes).

0.
09% cyclosporine eye drops from Kangzhe Pharmaceuticals

However, during the China Phase III bridging trial of the drug in May 2021, Kangzhe Pharmaceutical received a notice from Sun Pharma that "in view of the abnormal particle and content values that occurred, a batch of 0.
09% cyclosporine eye drops
will be voluntarily recalled in the United States.
" "Since the batch is the same batch of products used in China's bridging test, the company decided to take the initiative to suspend the China Phase III bridging test and start the bridging test
after receiving a new batch of test products that meet the company's quality requirements.
"

Therefore, the company decided to voluntarily suspend the China Phase III bridging test

Hengrui Pharmaceutical's SHR8028 (CyclASol, 0.
1% cyclosporine A preparation) and SHR8058 (NOV03, perfluorohexyl octane) are authorized from Novaliq in Germany, with indications for dry eye disease (dry corneal heliosis) and dry eye disease related to meibomian gland dysfunction, both of which are currently in the clinical phase III stage, and are expected to submit a listing application
as soon as the end of 2022.

Hengrui Pharmaceutical's SHR8028 (CyclASol, 0.
1% cyclosporine A preparation) and SHR8058 (NOV03, perfluorohexyl octane) are authorized from Novaliq in Germany to introduce these two drugs are currently in the clinical phase III stage, and are expected to submit marketing applications
as soon as the end of 2022.

Among them, SHR8028 is a transparent cyclosporine A ophthalmic solution, which is one of the drugs developed based on TheeSol®, the world's first anhydrous drug delivery technology platform, and its potential advantages include significant advantages such as high local bioavailability, fast onset of action, good local tolerance, etc.
, and reducing visual interference related to oily eye drops, emulsions or ointments; SHR8058 is a single-component perfluorohexyl octane (F6H8) sterile eye drops, one of the drugs developed based on the world's first anhydrous drug delivery technology platform EyeSol®, with a dual-action mechanism, which can stabilize the tear film, prevent excessive evaporation of tear fluid, and promote the recovery
of blepharmate secretion function of the meibomian gland.

®®

Different from the BD strategies of Hebo Pharmaceutical, Kangzhe Pharmaceutical and Hengrui Pharmaceutical, Zhaoke Ophthalmology's cyclosporine A ophthalmic gel is a class 2.
2 improved new drug developed by the company, and the new drug application has been accepted by the State Food and Drug Administration CDE on June 8, 2022, and will be approved for listing
soon.

Different from the BD strategy of Hebo Pharmaceutical, Kangzhe Pharmaceutical and Hengrui Pharmaceutical, the new drug application has been accepted by the CDE of the State Food and Drug Administration on June 8, 2022, and will be approved for listing
soon.

According to the announcement, unlike the Restasis emulsion formula, cyclosporine A ophthalmic gel uses hydrogel, which has multiple advantages
such as improved bioavailability and convenient administration.
Because the unique formulation of cyclosporine A ophthalmic gel can stay on the ocular surface for a longer period of time and only need to be administered once a day, unlike the previous therapy that generally requires 2 doses per day, the treatment time is greatly shortened
.

Only one dose per day is required

epilogue

epilogue

In summary, affected by the increasing number of patients and unmet clinical needs, the current domestic dry eye drug market shows good growth prospects
.

At the same time, with the continuous acceleration of the research and development of dry eye disease drugs in domestic pharmaceutical companies, a huge market change is beginning
.
It depends on who successfully card slots in this great change and grabs a place
.

【References】

【References】【References】

1.
"2022 Ophthalmology Industry Research Report: 100 Billion Market, Golden Track, Innovation Wins", Eggshell Research Institute

1.
"2022 Ophthalmology Industry Research Report: 100 Billion Market, Golden Track, Innovation Wins", Eggshell Research Institute

2.
"Xingqi Eye Drugs - 300573 - Ophthalmic Drug Leader, First Mover Advantage", Soochow Securities

2.
"Xingqi Eye Drugs - 300573 - Ophthalmic Drug Leader, First Mover Advantage", Soochow Securities

3.
"Self-research or introduction, the domestic dry eye drug market war has been ignited!" Sina Pharma

3.
"Self-research or introduction, the domestic dry eye drug market war has been ignited!" Sina Pharma

4.
Financial reports and announcements of each company

4.
Financial reports and announcements of each company