Introduction: Suginumab developed by Novartis Pharmaceutical Group (Novartis) in Switzerland is a breakthrough drug for the treatment of psoriasis in recent years. In January 2015, the U.S. Food and Drug Administration (FDA) approved the marketing of suginmab for the treatment of moderate to severe plaque psoriasis in adults. Since then, synthromumab has been approved for listing in Switzerland, Canada, the United Kingdom, the European Union, Japan, Hong Kong, Singapore, the Philippines, India and other places. Phase III clinical trials have shown that suginmab significantly improves skin symptoms, outperforming two other best-selling drugs: Johnson & Johnson's Stelara and Amgen's Enbrel. Let's get closer to this star drug through this article.
Psoriasis, commonly known as psoriasis, is a common chronic immuno-inflammatory disease with a global incidence of 2% to 3% and a continental incidence of 0.47% to 0.59%. Its main symptoms are skin diseases, which can be divided into plaque psoriasis, pustular psoriasis, erythroderma psoriasis, arthropathy psoriasis, etc. according to the different pathogenic characteristics, of which plaque psoriasis is the most common in the clinic. Different types of psoriasis may occur in the same patient and often require lifelong treatment due to stubborn conditions. Psoriasis is a T-cell-mediated autoimmune skin disease caused by a variety of pathogenic factors stimulating the body's immune system in a polygenic genetic background, and its pathogenesis has not been fully elucidated[1]. Traditional drugs for the treatment of psoriasis include methotrexate, sulfasalazine, avi A, etc., but some patients have poor effects or cannot tolerate adverse reactions after using the above drugs, so there is an urgent need for new psoriasis treatment drugs.
1. Psoriasis treatment target interleukin (IL) receptor
The IL (Interleukin) family, as one of the drug treatment targets for psoriasis, has been valued by researchers. Patients with psoriasis have a large number of T cell infiltrates and inflammatory chemokines in the lesions. Under the action of chemokines, peripheral blood T cells undergo directional chemotaxis and local tissue infiltration[2].
At present, the IL inhibitors that have been listed in the treatment of psoriasis worldwide are suginmab, Utexumab, exclimab, brodazumab, gousecumab, Tildrakizumab, and Risankizumab, Bimekizumab, Mirikizumab, CJM112, COVA322, ABT-122, ALX-0761, CNTO-6785 and NI-1401 are still in clinical trials. There are no IL inhibitors approved for marketing in mainland China, the IL-17A inhibitor SHR-1314 developed by Jiangsu Hengrui Pharmaceutical Co., Ltd. is currently in the clinical trial stage, and the sujinmab of Beijing Novartis Pharmaceutical Co., Ltd. and the exclimumab of Eli Lilly Suzhou Pharmaceutical Co., Ltd. are also in the clinical trial stage.
2.IL-17A and its receptor antagonists
2.1 Suginumab
Scukinumab (Secukinumab), commonly known as "sukinumab", trade name Cosentyx, is an IL-17A inhibitor developed by Novartis for the treatment of psoriasis. Synkinumab is a highly affinity, fully humanized immunoglobulin (Ig) G1κ antibody that selectively binds to IL-17A, preventing IL-17A from binding to its receptors, thereby preventing an inflammatory response that can cause psoriasis. In January 2015, the US FDA approved suginmab for the treatment of moderate and severe plaque psoriasis in adults, and in 2016, new indications for the treatment of psoriatic arthritis were added.
Two 52-week phase III placebo-controlled trials (ERASURE trial and FIXTURE trial)[3] affirmed the efficacy of suginmab against moderate and severe plaque psoriasis. The results of the FIXTURE trial showed that suginumab (300 mg or 150 mg once a week for 5 weeks and then every 4 weeks) was better than etanercept (50 mg twice a week for 12 weeks and then once a week) and placebo. After 12 weeks, the response rates of patients in the 300 mg group of suginmab, the 150 mg group of suginmab, the etanercept group and the placebo group were 77%, 67%, 44% and 5%, respectively, and the differences in the 300 mg/150 mg group of suginmab were statistically significant. Other studies have confirmed that suginmab is more effective than Utexumab for moderate and severe plaque psoriasis, and the safety of the two is similar.
2.2 Aiximab
Exclimumab is a humanized anti-IL-17A monoclonal Ig G4 antibody that selectively binds to and neutralizes IL-17A, blocks keratinocytes from producing β-prosintins, cytokines, antimicrobial peptide cytokines and chemokines, and reduces the degree of psoriasis lesions. In 2016, the US FDA approved exclimumab for the treatment of adult patients with moderate and severe plaque psoriasis.
2.3 Brodazumab
Brodazumab is a humanized IgG2 monoclonal antibody against the IL-17A receptor that binds to and blocks the signal through the IL-17A receptor, effectively alleviating psoriasis. On February 15, 2017, the US FDA approved brodazumab for the treatment of adult patients with moderate and severe plaque psoriasis, which is indicated as patients who can receive systemic therapy or light therapy and other systemic therapy is ineffective or ineffective.
In summary, a large number of meta-analyses have shown that [4] suginmab has become a star drug that has attracted much attention because of its effectiveness and safety, both in the same type of IL-17A drug and other drugs for the treatment of psoriasis.
3. The listing process of sucinumab
Suginmab is the world's first and only fully human monoclonal antibody drug specifically targeted to inhibit IL-17A, with approved indications for psoriatic arthritis (PsA), plaque psoriasis (PsO), ankylosing spondylitis, and axial spondyloarthritis. In June 2015, the European Medicines Agency (EMEA) recommended approval of suginumab for the first-line treatment of psoriasis. In March 2019, sulkumab was approved by the Mainland State Drug Administration (NMPA) for the treatment of plaque psoriasis (PsO). In June 2020, the U.S. FDA approved treatment for patients with active radiologically negative axial spondyloarthritis (nr-axSpA). In July 2020, suginumab was approved by the National Drug Administration (NMPA) of the mainland for use in adult patients with ankylosing spondylitis (AS) with poor conventional treatment. The National Medical Security Bureau of the Mainland released the results of the 2020 National Medical Insurance Drug Catalogue Adjustment Negotiations, and the biological agent of psoriasis - Novartis Pharmaceutical Suginumab (Keshan Ting) successfully entered the medical insurance, and the price was greatly reduced!
4. Dosage and usage of sucinumab
The standard regimen of administration of suginumab approved by the US FDA is: 300 mg subcutaneously once a week at weeks 0, 1, 2, 3, and 4 weeks, and then 300 mg every 4 weeks.
5. Anti-psoriasis drugs that are contested by hundreds of schools
At present, the market for psoriasis treatment drugs is full of smoke, not only a new generation of new drugs competing with each other, but also against the blockbuster Humira, Enbrel, Remicade, Stelara and other biosimilars. Meanwhile, Novartis, Singy, Amgen, AstraZeneca, Cipla and others will collectively compete for the $10 billion psoriasis treatment market. To win this competition, pharmaceutical companies will not only have to prove the advantages of their respective products in terms of efficacy and safety, but also the portability and price of drug delivery will also play a big role. Currently, the psoriasis market is dominated by TNF blockers, but up to 40% of patients respond poorly or unresponsively to TNF blocker treatment, and the marketing of anti-IL-17A monoclonal antibodies, especially suginumab, which is the best of its kind, will greatly improve the clinical standard of care for psoriasis, psoriatic arthritis, and other inflammatory diseases.
6. Prospects and outlook
The current market for psoriasis treatment drugs is similar to the hepatitis C treatment drug market a few years ago, and in the current high-quality/high-price payment environment, new drugs with significant efficacy and convenient administration can expand and occupy the market to a large extent compared with the current treatment gold standard. As mentioned above, synkinumab has been shown in several clinical trials to have better efficacy compared to bombshell Enbrel. It is expected that the psoriasis treatment drug market may be the same as the hepatitis C treatment drug market in that year, and the total market capacity will soon exceed the $10 billion mark. It is believed that new molecular targets and the accompanying available biomarkers in the future will bring hope for the precise treatment of psoriasis.