Chinese And Foreign Pharmaceutical Companies Compete To Enter The AD Treatment Field, Is It Expected To Give Birth To A New "Drug King"?

On the eve of "world atopic dermatitis day" on September 14, good news came from the field of atopic dermatitis treatment. First, Sanofi "dabituo" (dupulizumab) was approved as a new indication in China, and soon afterwards, cibinqo (abrocitinib), a Pfizer Jak1 inhibitor, was launched in the UK. So it is not difficult to find that the market competition of atopic dermatitis is increasingly fierce.

At present, type 2 inflammatory disease with atopic dermatitis as the first symptom has become a new health challenge for Chinese people. Especially at the beginning of school season, some teenagers are facing skin health problems such as pruritus and skin lesions.

Guo Yifeng, deputy director of the Department of Dermatology, Xinhua Hospital Affiliated to Shanghai Jiaotong University Medical College, told reporters in an interview with 21st century economic news that atopic dermatitis is a chronic recurrent and inflammatory skin disease, and its most prominent clinical manifestations are pruritus and recurrent eczema like lesions. The World Health Organization has done a study on the burden of disease. The results show that atopic dermatitis ranks 15th among all chronic diseases and the first among all skin diseases.

"The proportion of adolescents in outpatient service is about 40%, but in fact, the prevalence of atopic dermatitis is the highest in infancy, and it gradually decreases with the increase of age. In this group of adolescents, this kind of patients account for about 15% - 20% of all patients who come to see a doctor. This requires clinicians and patients to start standardized treatment from childhood, which also needs to be effective for atopic dermatitis There are more and more safe drugs, "Guo said.

In fact, the chief analyst of the pharmaceutical industry of a securities company also said in an interview with the reporter of the 21st century economic report that with the increase of the diagnosis and treatment rate of atopic dermatitis, the utilization rate of related drugs will continue to increase, and the market share of efficient and safe therapeutic drugs will be significantly increased, It is expected to further promote the standardized treatment and clinical rational drug use standard of atopic dermatitis.

Adolescents become a high incidence group of AD

Atopic dermatitis (AD) is a refractory systemic immune disease. In recent years, the prevalence of AD has been increasing, especially in adolescents. It is estimated that the prevalence of atopic dermatitis in adolescents is 0.2% - 24.6% worldwide.

In addition, according to the relevant data, atopic dermatitis accounts for about 10% of the outpatients in the dermatology department of the hospital, while the prevalence rate of ad in children is about 15% - 20% and that in adults is 1% - 3%. Based on this, the incidence of ad in China is estimated as 17% in children and 2% in adults, although the number of potential patients is about 66.6 million, However, the correct diagnosis rate and standardized treatment rate are still the main market resistance. According to 90% treatment rate, the domestic ad market has about 5.99 million people.

Guo Yifeng told the 21st century economic reporter: "compared with adults, teenagers are more concerned about skin diseases, and they are more difficult to bear the huge pain caused by itching and pain caused by long-term illness. As a result, their quality of life is often unsatisfactory compared with their peers."

According to the Research Report on the living conditions of atopic dermatitis patients in China released by the China Association for health promotion and education, 46% of adolescent patients with atopic dermatitis are affected by acute attack, and more than 50% of them have low self-confidence, fear of social intercourse and even have depression symptoms. It should be noted that patients often have allergic rhinitis, asthma and other type 2 inflammatory diseases, and patients with moderate to severe atopic dermatitis have a higher risk of atopic comorbidity, and the burden of the disease is also heavier.

From the onset characteristics of adolescent patients, the most obvious symptoms are dry skin, chronic eczema like lesions and obvious pruritus. Compared with childhood patients, the onset site of adolescent patients is more diffuse, skin lesions mainly occur in the elbow fossa, popliteal fossa, anterior neck and other parts, but also in the trunk, limbs, face and hands exposed parts.

"Among the patients who come to the dermatology clinic, there are not a few teenagers. One of the most important problems that atopic dermatitis brings to them is the influence on their external image. Children who are in adolescence also pay more attention to the opinions of people around them, so it is easy to create psychological burden," Guo Yifeng pointed out.

Chinese and foreign pharmaceutical enterprises compete to enter the Bureau

In addition to paying attention to clothing, food, housing and transportation, under the background of the increasingly heavy burden of atopic dermatitis, the treatment of atopic dermatitis has become a hot topic in the industry, which also drives the market development of atopic dermatitis disease treatment.

Recently, the National Drug Administration (nmpa) official website showed that Sanofi "dabituo" second indication was approved for the treatment of moderate and severe atopic dermatitis in adolescents and adults aged 12 and above who are poorly controlled or do not recommend the use of topical prescription drugs. Prior to this, the listing application of the indication was included in the priority review.

Up to now, "dabitor" has been applied to moderate and severe atopic dermatitis in China, covering children and adults aged 6 and above.

In China, "dabitol" was approved for the first time in June 2020 for the treatment of moderate to severe atopic dermatitis in adults with poor control of topical prescription drugs or not recommended to use topical prescription drugs; In October 2020, the marketing application of "dabitor" for the treatment of moderate to severe atopic dermatitis in patients aged 12 years and above was included in the priority review by CDE; In June 2021, the marketing application of "dabitor" for the treatment of moderate and severe atopic dermatitis in children and adults aged ≥ 6 to < 12 years was included in the priority review by CDE.

The launch of the drug also contributed a good report card to Sanofi. According to Sanofi's financial report for the second quarter of 2021, during the reporting period, the global sales of Sanofi's atopic dermatitis drug doprizumab increased by 56.6% to 1.24 billion euros (US $1.47 billion). In addition, to date, Frost & Sullivan predicted that with the continuous expansion of indications and IL-4R α The penetration rate of targeted drugs is increasing, and it is estimated that by 2030, IL-4R α The global market is 28.7 billion US dollars.

It is reported that domestic pharmaceutical enterprises, including Cornell, kangyanuo, AstraZeneca, kangfang biology, Shengxin biology and Maiji biology, are also focusing on this market potential α Drug market, and are in clinical and above stage. For example, Conoco's cm310 is the first domestic and approved clinical IL-4R α The indications for the treatment of atopic dermatitis have entered clinical stage II in China. It is expected that NDA application will be submitted to nmpa in 2023; The indications for the treatment of chronic sinusitis are expected to start phase III clinical practice in 2022.

In addition to the targeted biological agents represented by "dabituo", immunosuppressants and hormone drugs are also used to treat atopic dermatitis. Recently, Pfizer announced that the United Kingdom drug and Health Products Administration (MHRA) has approved cibinqo (abrocitinib), an oral Jak1 inhibitor, for the treatment of moderate to severe atopic dermatitis in adults and adolescents over 12 years old who are suitable for systemic treatment. In addition, in the JAK inhibitor market, there are also enterprises such as Abbott, Eli Lilly, Amgen, Hengrui pharmaceutical, etc., which have been stepping up the layout.

"Under the extensive market demand, pharmaceutical companies are also increasingly interested in R & D. with the approval of innovative drugs, there are also potential to appear in the field of atopic dermatitis treatment, such as Abbott maintenance Merlot The above chief analyst pointed out that with the continuous increase of clinical indications and market expansion of various pharmaceutical companies, the market scale of atopic dermatitis will be further expanded, especially with the support of targeted biological agents such as duprilimab, the market of therapeutic drugs for atopic dermatitis will become a big red sea.

JAK inhibitors are warned by FDA

However, with the rapid development of drug research and development, how to standardize drug use has become a major problem for patients. This has also become one of the most concerned topics of clinical and patients.

According to the report on the survival of patients with atopic dermatitis in China, more than 50% of doctors have used systemic treatment such as glucocorticoids and immunosuppressants. However, 75.7% of the doctors were not satisfied with the existing treatment plan, which was mainly reflected in the poor treatment effect and more adverse reactions.

This can also explain why the U.S. Food and Drug Administration (FDA) recently required that JAK inhibitors, including Pfizer xeljanz, Alberto rinvoq and Lilly Olympian, be clearly labeled so that patients have heart safety and cancer risk after treatment.

According to public information, these drugs have previously had a black box warning of thrombosis and lymphoma. Affected by the new safety warnings, FDA has delayed the sequential placement of these drugs in the treatment of indications, and restricted the use of these drugs in all approved indications to patients who have failed or are not suitable for TNF blockers. The news also prompted analysts to sharply lower their long-term sales expectations of irbvir star immunology drug rinvoq.

In response, Guo Yifeng told reporters in the 21st century economic report that the current main treatment methods include: first, basic treatment, for all patients with atopic dermatitis, mainly skin care; The second is topical therapy. According to the type, location and severity of the rash, different dosage forms or intensity of topical drugs should be selected; In addition, if the external use of drugs can not completely control the symptoms, we will consider the use of systematic treatment such as phototherapy, three times a week is recommended; In addition, if phototherapy is ineffective, immunosuppressive therapy is often considered.

"The main advantage of immunosuppressants is that they work faster, but their biggest problem is also their safety. Relatively speaking, they have a significant impact on liver and kidney function, bone marrow and blood picture. Once immunosuppressants are used, we need to closely monitor whether there will be adverse reactions," Guo said, For some particularly refractory severe atopic dermatitis, short-term systemic glucocorticoid therapy may also be considered. But in clinical practice, it will not be used in this way, which is also due to the frequent use of hormones will lead to abnormal growth and development.

"Immunosuppressive agents such as JAK can not only play a role in atopic dermatitis, but also affect red blood cells, white blood cells, B lymphocytes and other cells. Therefore, the role of immunosuppressants is very wide. At the same time, immunosuppressive agents can also produce adverse reactions in various systems after using immunosuppressive agents For example, dupulizumab is mainly targeted at two types of inflammation, interleukin-4 and interleukin-13, but its safety is better than that of immunosuppressants, "Guo Yifeng added.

In the market of atopic dermatitis drug treatment, both immunosuppressive agents and hormones have great potential safety risks, which also provides a competitive opportunity for targeted biological agents and even more new drugs in the future.