"Butterfly spots" caused by systemic lupus erythematosus,* uptodate
After the sudden death of 57-year-old Hong Kong star Zhou Haimei, systemic lupus erythematosus (SLE) has recently rushed to the hot search on social platforms many times, causing high attention in the market.
The focus of the hot discussion is the "difficulty" of systemic lupus erythematosus, which is difficult to diagnose clinically and is also difficult. Due to the complexity and diversity of symptoms, the symptoms of 100 patients with SLE may be different, and the onset of SLE is insidious and complex, which makes it difficult to make a clinical diagnosisBecause it is "systemic", it is difficult to involve multiple systems and organs. Because it can't, systemic lupus erythematosus is also known as the "immortal cancer".
As a result, most patients "talk about wolf discoloration". However, experts also called for no panic, and Huang Cibo, vice chairman of the Chinese Society of Rheumatology, emphasized: "As long as early screening, early investigation, early diagnosis, and early treatment are achieved, systemic lupus erythematosus can be prevented and treated." ”
In addition, CAR-T** is expected to bring the first light at the end of the tunnel for SLE. CAR-T** starts from SLE pathogenic B cells, bringing a new "solution" to the disease. There are academic studies that have proven that CAR-T** is expected to be safe and efficient for single-use**SLE.
Different from the superficial meaning of its name, systemic lupus erythematosus is not a ** disease, but an autoimmune disease involving multiple systems and organs, and patients have symptoms such as fever, fatigue, joint swelling and pain, kidney disease, and lupus pneumonia, which can lead to serious organ damage, complications and even death**Complex, related to genetics, environment, sex hormones and other factors.
According to public data, there are more than 1 million SLE patients in China, ranking second in the world, and about 7.8 million patients in the world. Most of the patients are women of childbearing age aged 20-40, and the changes in appearance and impaired reproductive function seriously affect the quality of life of patients, so there is a very urgent will.
For systemic lupus erythematosus, commonly used methods include hormones, antimalarials, immunosuppressants, and biologics.
Among them, glucocorticoids, immunosuppressants and other traditional ** accompanied by serious *** glucocorticoids are common***, including hypertension, hyperglycemia, peptic ulcers, etc., and immunosuppressants have toxic effects on liver and kidney functionHydrochloroquine, which is commonly used in clinical practice, also has adverse reactions.
According to data from the China Systemic Lupus Erythematosus Research Collaboration Group (CSTAR), 84Thirteen percent of patients with SLE are taking corticosteroids**, and some of them are taking high doses of hormones for maintenance**, and adverse effects increase with increasing doses.
With the approval of biologics, it can further reduce the dependence of SLE patients on corticosteroids.
In July 2019, the world's first biologic, "Belimumab for Injection" (commercial name: Beliteng), was approved by the State Food and Drug Administration for marketing in ChinaUS) for adult patients with active, autoantibody-positive systemic lupus erythematosus who still have high disease activity on a routine basis.
Tetatercept for injection, ** in Rongchang Biologics.
In March 2021, the world's first "dual-target" biologics for the treatment of ** systemic lupus erythematosus, "Tatanercept for Injection" (trade name: Taiai), was conditionally approved for marketing by the State Food and Drug Administration, and in late November this year, Taiai was fully approved by the State Food and Drug Administration 688331 for marketingSH) R&D and production.
It is understood that Tatanercept inhibits the overexpression of two cytokines, BLYs and April, inhibits the maturation and differentiation of abnormal B cells, thereby reducing the body's autoimmune response and achieving the purpose of delaying disease progression and reducing **.
Production and sales of tetanercept for injection in 2022, ** in the annual report of Remegen.
From the increase in sales of "tetanercept for injection", it can also be seen to a certain extent that the shortage of drugs for systemic lupus erythematosus and the urgency of the willingness. According to the annual report of Remegen, the production volume and sales volume of "Tatanercept for Injection" in 2022 will be 54150,000, 49080,000, a year-on-year increase. 51%。
It is worth mentioning that in December 2021, Tatanercept was officially included in the medical insurance catalog, and in December this year, Tatanercept renewed the new version of the medical insurance catalog.
However, there are less than 5 drugs approved for the use of ** systemic lupus erythematosus in the world, and only the above two biologics have been approved in China. The main reason for the small number of approved SLE drugs is the diversity of clinical symptoms and the complexity of SLE, which make it difficult to enroll, design and verify the effectiveness of drugs.
According to publicly available information, one of the core hallmarks of SLE is the breakdown of B cells' own tolerance, which leads to abnormal activation and the production of a large number of autoantibodies.
According to the analysis of Huachuang** analysts, CAR-T** has been widely used in B-cell tumors** before, and is expected to achieve the effect of deep clearance of SLE pathogenic B cells, triggering immune "reset", so as to achieve complete remission of the disease (i.e., no drug remission).
Two academic studies in China and overseas included 13 and 7 patients with severe refractory SLE, respectively, and the results showed that CAR-T***SLE is expected to be safe and efficient to achieve one-time **: after 80% of patients, the SLEDAI-2K score was reduced to 0 points (3 patients with 4 points had proteinuria and hematuria due to permanent kidney injury, and other SLE symptoms had been eliminated), and autoantibodies achieved seronegative and achieved durable remission for up to 44 months (nearly 4 years). All patients did not require hydroxychloroquine, hormones, or immunosuppressants**, achieving a near-one-off** effect.
This is undoubtedly exciting news. However, industry insiders also said that further research is needed on the long-term efficacy and safety of CAR-T cells** for SLE patients, and the feasibility of the ** also needs to be further verified.
At present, many companies have "sniffed" this emerging technology and have launched a layout, and China's pharmaceutical companies are expected to take the lead. According to Huachuang** data, JW Therapeutics (02126HK) is currently in clinical trialsGracell has achieved initial positive data from CD19 BCMA dual-target CAR-T**SLE in vitro studies and IIT, which will be published in the first half of next year.
*On the official website of Gracell Biotech.
In addition, BMS and Novartis have developed CD19 CAR-T for autoimmune diseases using a newly developed accelerated manufacturing platform, both of which have entered Phase I clinical trials and are expected to read out next yearCabaletta Bio's CD19 CAR-T is being developed in a Phase I II SLE clinical trial using a reindeer bio-licensed sequence and has been granted Fast Track Designation by the FDA.
Although most of the above-mentioned R&D pipelines are in preclinical studies, they have finally taken a big step forward in the "difficult problem" of systemic lupus erythematosus.
This article was first published in Titanium**app，AuthorZhang Haixia