@Lupus and psoriasis patients, 8 "new medicines" are here!

It is only for medical professionals to read and reference.
This issue of "New Drugs Is Coming" counts the three important areas of autoimmune diseases, and the drugs that have obtained important approval information and research progress in August are for readers
.

Editor's note: In recent years, due to the improvement of medical technology and level at home and abroad, autoimmune diseases have increasingly become a disease field of concern to society, doctors, and patients
.

With the in-depth exploration of disease mechanisms and therapeutic targets, innovative therapeutic drugs for autoimmune diseases are emerging with each passing day
.

This issue of "New Drugs Coming" counts the three important areas of autoimmune diseases, and the drugs that have obtained important approval information and research progress in August are for readers
.

1 Systemic lupus erythematosus In recent years, inhibitors aimed at various targets have been testing the field of systemic lupus erythematosus (SLE).
Currently, in China, the only biologics used for SLE indications are belimumab and taita Cipro, in addition to rituximab, which is an off-label medication
.

What are the recent developments in the field of SLE? Let's look internationally! On August 2, 2021, AstraZeneca announced that Saphnelo (anifrolumab-fnia) has been approved by the U.
S.
Food and Drug Administration (FDA) for use in adult patients with moderate to severe SLE who are also receiving conventional treatment
.

Saphnelo is a "first-in-class" drug targeting type I interferon receptors, marking the first time that a type I interferon receptor antagonist has received regulatory approval
.

This is also the first new drug approved by the FDA 10 years after GSK's beliyuumab was approved for SLE indication in 2011
.

Type I interferon is a type of cytokine involved in inflammatory response and plays a central role in the pathophysiology of lupus
.

60%-80% of SLE patients have high expression characteristics of type I interferon, and the level of type I interferon is positively correlated with the severity of the disease in SLE patients
.

Saphnelo can bind to subunit 1 of type I interferon receptor, thereby antagonizing all activities related to type I interferon (IFN-α, IFN-β and IFN-ω)
.

Figure: Saphnelo's mechanism of action Saphnelo was approved based on its clinical efficacy and safety data, including 2 phase 3 clinical studies named TULIP and 1 phase 2 clinical study named MUSE
.

The TULIP 1 study used SRI-4 to evaluate the efficacy of Saphnelo in reducing disease activity.
Although the study did not meet the primary endpoint of SRI-4, 300mg Saphnelo compared with placebo achieved multiple overall and organ-specific secondary endpoints (including BICLA improvement, CLASI), hormone reduction in relapse rate, reduced joint swelling and pain and other aspects of the count
.

2 Psoriasis With the approval of a series of interleukin (IL) inhibitors, the field of psoriasis has also entered a "booming era" of biologics
.

At present, in China, there are tumor necrosis factor inhibitors (TNFi: adalimumab, infliximab, etanercept), IL-17A inhibitors (skukuzumab, ezizumab), IL -23 inhibitor Gusekizumab and IL-12/23 inhibitor Uselumumab have been approved for the treatment of psoriasis in four categories of biological preparations; it is worth mentioning that an oral small-molecule targeted drug, Apumi Ster has also recently been approved in China for systemic treatment of psoriasis
.

■ PDE-4 inhibitor-Apomilast On August 16, 2021, the latest announcement by China National Medical Products Administration (NMPA), Amgen Apomilast (also known as apremilast) has officially Approved in China
.

Image source: NMPA official website Apomilast is a new type of oral small molecule phosphodiesterase 4 (PDE-4) inhibitor, which exerts its effect by inhibiting the release of tumor necrosis factor (TNF)-α from human synovial cells in a dose-dependent manner Role
.

In March 2014, Apomilast was approved for marketing in the United States for the first time.
The indications that have been approved in the United States are: 1) Patients with moderate to severe plaque psoriasis suitable for phototherapy or systemic treatment; 2) Patients with moderate to severe plaque psoriasis suitable for phototherapy or systemic therapy; Adult patients with active psoriatic arthritis; 3) Adult patients with oral ulcers associated with Behcet’s disease
.

Previously, a multicenter, randomized, placebo-containing phase 3 clinical study called ADVANCE reached its primary endpoint
.

Compared with the placebo group, in the static doctor's overall assessment (sPGA) at week 16, Apomilast made a statistically significant improvement in the skin condition of patients with mild to moderate plaque psoriasis
.

Many studies suggest that Apomilast has been proven to have a therapeutic effect and is well tolerated in studies outside China.
It is administered by oral route and has a new target of action
.

It is believed that the arrival of Apomilast will enable Chinese patients with psoriasis to increase new treatment options
.

■ Benvimod On August 10, 2021, the FDA stated that it has accepted the New Drug Application (NDA) of Dermavant Sciences' investigational therapy tapinarof topical cream for the treatment of plaque psoriasis in adults
.

Tapinarof emulsion is an aromatic hydrocarbon receptor modulator (TAMA) used to treat plaque psoriasis and atopic dermatitis, which is administered once a day
.

Aromatic hydrocarbon receptors play an important role in regulating autoimmune responses
.

By regulating the function of aromatic hydrocarbon receptors, Tapinarof can inhibit IL-17-mediated inflammation
.

This innovative treatment was first approved for marketing in China in 2019, named benvitimod cream, and has been included in the 2020 medical insurance drug catalog
.

Tapinarof's molecular structure (source: Edgar181, Public domain, via Wikimedia Commons) This application benefited from the positive data obtained from two phase 3 clinical trials PSOARING 1 and PSOARING 2, and the mid-term results of the long-term safety study PSOARING 3
.

The results of the test showed that about one-fifth of patients reached the standard of more than 90% improvement in psoriasis lesion area and severity index (PASI 90) after receiving Benvimod for 12 weeks
.

■ IL-17A/IL-17F inhibitor-bimekizumab At the beginning of September 2021, Bimzelx (bimekizumab), a subsidiary of UCB, was approved by the European Commission for the treatment of patients with moderate to severe plaque psoriasis.
This is the first IL-17A/IL-17F inhibitor approved for the treatment of psoriasis
.

The fully humanized monoclonal antibody bimekizumab can strongly and specifically neutralize IL-17A and IL-17F
.

IL-17A plays a key role in the pathogenesis of plaque psoriasis, psoriatic arthritis and ankylosing spondylitis
.

IL-17A and IL-17F have more than 50% structural homology and overlapping biological functions
.

IL-17A and IL-17F are up-regulated in a variety of inflamed human tissues, and cooperate with other pro-inflammatory cytokines, such as tumor necrosis factor (TNF), to amplify the inflammatory response
.

Combining these two cytokines at the same time prevents them from interacting with the IL-17 receptor expressed on the cell surface, so that bimekizumab can better exert its anti-inflammatory function
.

The approval of the target of bimekizumab is mainly based on the three phase 3 clinical trials BE VIVID, BE READY and BE SURE, all of which reached the common primary and key secondary endpoints of the trial
.

The results showed that all patients treated with bimekizumab had better improvement in skin lesion clearance (PASI 90 and IGA 0/1) than conventional psoriasis treatment/placebo treatment
.

3 The book on atopic dermatitis continues from the above.
If there are already an endless stream of innovative drugs in the field of psoriasis in China, then the field of atopic dermatitis (AD) is Moncorroque
.

Up to now, the only bio-innovative drug approved in China for the treatment of AD system is duplizumab, ■ IL-13 inhibitor-lebrikizumab On August 16, 2021, Eli Lilly and Company announced that it is an IL-13 inhibitor lebrikizumab, in two pivotal phase 3 clinical trials ADvocate 1 and ADvocate 2 reached the primary endpoint and all key secondary endpoints
.

The results of the trial showed that compared with placebo, lebrikizumab improved the skin lesions of more than half of moderate to severe AD patients by at least 75% (EASI 75)
.

In addition, the patient’s pruritus symptoms, pruritus-related sleep and quality of life were significantly improved; the safety was consistent with previous studies
.

Lebrikizumab binds IL-13 with high affinity and specificity, thereby preventing the formation of IL-13Rα1/IL-4Rα complex and inhibiting the signal pathway mediated by this receptor complex
.

Prior to this, lebrikizumab has obtained fast-track qualification granted by the FDA for the treatment of adults and adolescents with moderate to severe AD
.

The mechanism of action of antibody therapy targeting IL-4 and IL-13 signaling pathways (picture source: reference [2]) ■ JAK inhibitor-upatinib On August 24, 2021, AbbVie announced that the European Union The committee approved its oral JAK inhibitor upadacitinib (upadacitinib; Rinvoq) to expand its indications for the treatment of moderate/severe AD patients suitable for systemic therapy in adults and adolescents over 12 years old.
) Combined use
.

Molecular structure of upatinib According to reports, upatinib is the first JAK inhibitor approved for the treatment of AD and has reached all primary and secondary endpoints in a number of phase 3 clinical trials
.

Compared with placebo, whether as monotherapy or in combination with TCS, patients in the upatinib group showed rapid and significant improvement in skin clearance and relief of itching (p<0.
001)
.

The JAK protein family mediates the signal transduction of a variety of inflammatory factors
.

In cell experiments, upatinib preferentially inhibits JAK1 or JAK1/3 signal transduction
.

In August 2019, the FDA approved upatinib for the treatment of moderate to severe adult patients with active rheumatoid arthritis who are inadequate or intolerant to methotrexate
.

In addition, upatinib has obtained positive results in phase 3 clinical trials of various inflammatory diseases such as ankylosing spondylitis, ulcerative colitis, and psoriatic arthritis
.

■ IL-4 and IL-13 inhibitors-Dupilumab On August 30, 2021, Sanofi announced that dupilumab (dupilumab) will be treated for 6 months to 5 years old.
The primary endpoint and all secondary endpoints were achieved in a pivotal phase 3 clinical trial in children with severe AD
.

The data shows that at week 16, compared with standard treatment, the addition of prijuzumab to topical corticosteroids (TCS) significantly reduced the patient's overall disease severity and significantly improved the patient's skin Symptom clearance, itching, and health-related quality of life indicators
.

Duplizumab inhibits the signal transduction of interleukin-4 (IL-4) and interleukin-13 (IL-13) pathways, and has been approved in China in 2020 for the treatment of moderate to severe AD in adults.
And it will be included in medical insurance in March 2021
.

In June 2021, the drug also obtained the new indication priority review qualification from the Center for Drug Evaluation (CDE) of the National Medical Products Administration of China for the treatment of 6-year-olds who have poor control of external prescription drugs or who are not recommended to use external prescription drugs.
Children and adults over and under 12 years old have moderate/severe AD
.

IL-4 and IL-13 are the core factors and driving factors of type 2 inflammation in AD.
On September 9, 2021, the latest announcement of NMPA, the new indication of Duplizumab for adolescents, has been officially approved for use in For adolescents 12 years and older and adults with moderate to severe AD
.

Screenshot source: NMPA official website ■ JAK 1 inhibitor-Abrocitinib On August 30, 2021, Pfizer announced that the phase 3 clinical trial of the oral JAK 1 inhibitor Abrocitinib, JADE DARE, has reached common primary and key secondary efficacy endpoints
.

The test results show that compared with active control drugs, Abrocitinib has statistical superiority in each evaluated efficacy index, and has safety characteristics consistent with previous studies
.

JAK 1 inhibition is thought to regulate a variety of cytokines involved in the pathophysiology of AD, including interleukins IL-4, IL-13, IL-31, IL-22, and thymic stromal lymphopoietin (TSLP)
.

On October 28, 2020, the FDA accepted Abrocitinib's new drug application for the treatment of moderate to severe AD patients over 12 years old and granted it priority review
.

Previously, the drug was granted breakthrough therapy designation by the FDA
.

Molecular structure of Abrocitinib (Source: Edgar181, Public domain, via Wikimedia Commons) According to the New England Journal of Medicine, JADE COMPARE evaluated the effectiveness and safety of two doses of Abrocitinib in moderate to severe AD adult patients receiving topical therapy
.

The results showed that in the 12th and 16th weeks, Abrocitinib at a dose of 200 mg or 100 mg once a day compared with placebo can significantly reduce the symptoms and signs of moderate to severe AD
.

This issue of "The New Medicine Is Coming" comes to an end here, and see you in the next issue! Reference: [1]Saphnelo(anifrolumab)approved in the US for moderate to severe systemic lupus erythematosus.
Retrieved August 2,2021,fromhttps:// 2021/saphnelo-approved-in-the-us-for-sle.
html[2].
Timothy B.
Niewold.
et al.
(2016) Targeting type I interferon in systemic lupus erythematosus.
Nature reviews rheumatology.
https://www .
nature.
com/articles/nrrheum.
2016.
83[3]Dermavant Announces FDA Acceptance for Filing of New Drug Application(NDA) for Tapinarof Cream for the Treatment of Adults with Plaque Psoriasis.
Retrieved August 10,2021, from https://www .
dermavant.