Top 10 most ``beautiful'' clinical data in 2019

On the other hand, when people have a little aesthetic fatigue for PD-1 / PD-L1 or their attention has been shifted from PD-1 / PD-L1, some research and development progress and breakthroughs in other fields will be highlightedSo in 2019, we have seen the turn of over 30 years of KRAS inhibitors, the rise of RNA therapy and gene therapy, and the emergence of bispecific antibodies and ADC drugs , we are overwhelmed by hot news events, which are much more colorful than the monotony of PD-1 / PD-L1 dominating the circle of friends< br / > at the end of 2019, the magic cube of medicine screened the most "beautiful" clinical data of the year from nextpharma, taking you back to the major progress in the field of new drug research and development this yearThe so-called "Liang", on the one hand, means that these clinical research data are impressive and unforgettable; on the other hand, these clinical data can be considered as a major breakthrough in the treatment of a certain disease, the development of a certain target drug or a certain kind of drug< br / > 1 scuchiumab < br / > Company: Novartis < br / > mechanism: IL-17A monoclonal antibody < br / > disease: psoriasis < br / > research code: nct03066609 (phase III) < br / > on March 4, Novartis published a Chinese cohort data of cosentix phase III study (nct03066609) on the treatment of moderate and severe plaque psoriasis at aad2019 conference, It is the first time that the phase III study of cosentix and IL-17A monoclonal antibody for Chinese patients has appeared< br / > the study was a 52 week randomized, double-blind, placebo-controlled, international multicenter design441 Chinese patients with or without psoriatic arthritis were randomly divided into three groupsThey were given cosentix 300mg (n = 221), cosentix 150mg (n = 110) and placebo (n = 110) by subcutaneous injectionThe primary end points were PASI 75 and iga2011 0 / 1 at week 12The secondary end point was PASI 90 at week 12< br / > the results showed that cosentix had rapid effect and excellent effect in Chinese patientsThe improvement of the disease can be reflected in the third week of treatment, and the curative effect is more significant with the prolongation of treatment timeThe proportion of patients with PASI 75 was 97.7% and 80.9% of the patients reached PASI 90 at the 12th week in cosentix 300mg groupIn terms of safety, cosentyx was well tolerated, and the incidence of adverse events was consistent with previous studies< br / > the efficacy data of cosentyx for Chinese patients with psoriasis is surprisingIf compared with the previously published placebo-controlled clinical research data, the efficacy and safety of cosentyx for Chinese patients with psoriasis is still better than some international data (as shown in the table above), which is more difficult< br / > psoriasis is a chronic disease that can not be cured at presentThere are many patients in China, the number is close to 7 million, but the degree of concern is not high compared with cancerPsoriasis patients are more likely to suffer from depression, inferiority, anxiety, social fear and other psychological diseases due to the skin exposure and recurrent disease, which is also a great burden on family care< br / > however, for a long time, the first choice for psoriasis treatment in China is external medicine and phototherapy, followed by traditional medicine with large side effects such as methotrexate, cyclosporine and tretinoin, and biological preparation is usually the last choiceThe excellent data obtained by cosentix in Chinese patients and its approval for listing mark a new era of psoriasis treatment in China, which is expected to improve the treatment status of biological agents in China's psoriasis treatment and promote the progress of clinical treatment of psoriasis in China< br / > at the mid October eadv 2019 conference, the 52 week data of phase III study for Chinese patients was released by cosentixAlmost all patients who received 300mg treatment had stable effect within 52 weeks, and the proportion of patients who achieved PASI 90 and PASI 100 increased compared with the 12th week, suggesting that more patients could benefit from the long-term treatment of cosentityx< br / > 2 olapalin < br / > Company: AstraZeneca < br / > mechanism: PARP inhibitor < br / > disease: pancreatic cancer < br / > research code: Polo (phase III) < br / > on June 2, AstraZeneca announced the results of a phase III study of PARP inhibitor olapalin Code: polo at the ASCO 2019 conferenceIn polo study, 154 patients with BRCA mutation and metastatic pancreatic cancer who had not progressed after first-line platinum chemotherapy were treated with olaparide (300mg, bid) and placebo as first-line maintenance therapy until the disease progressedTo compare the efficacy and safety of olaparide and placebo in progression free survival< br / > the results showed that olaparide doubled the progression free survival time (7.4 vs 3.8 months) and the disease progression risk (HR 0.53), doubled the one-year progression free survival rate (33.74% vs 14.5%) and doubled the two-year progression free survival rate (22.1% vs 9.6%) compared with placebo< br / > the progression free survival data of polo study patients < br / > pancreatic cancer is a kind of tumor with very high malignancy and mortalityThe 5-year survival rate is only about 6% (2% - 9%), which is called "the king of cancer"Pancreatic cancer is very difficult to treatFor many years, the mainstream treatment plan is the combination of chemotherapy drugs based on gemcitabineThe improvement of survival of pancreatic cancer patients is very limitedThere is no obvious breakthrough in the past 20 years, and the clinical treatment needs are far from being met < br / > in terms of patient benefit, the BRCA mutation rate in pancreatic cancer is about 7% Polo study suggests that in patients with metastatic advanced pancreatic cancer with BRCA mutation, after obtaining valuable clinical remission with platinum containing chemotherapy, olaparide alone as the first-line maintenance treatment can significantly prolong the progression free survival period of the first-line treatment, not affect the quality of life of patients, and double the 2-year progression free survival rate, and increase the proportion of patients who can receive the second-line treatment, This is a major breakthrough in the clinical treatment of pancreatic cancer, and is of great significance for the patients with metastatic pancreatic cancer who are initially treated < br / > 3 amg-510 < br / > Company: Amgen < br / > mechanism: KRAS inhibitor < br / > disease: solid tumor < br / > research stage: phase I < br / > on June 3, Amgen orally reported the first human clinical trial results of KRAS G12C inhibitor amg-510 at ASCO 2019 Conference This open label phase I study included 35 patients with KRAS G12C mutant solid tumors who had previously received at least two lines of treatment, including 14 patients with non-small cell lung cancer, 19 patients with colorectal cancer, and 2 patients with other types of tumors According to the dosage, amg-510 was divided into 4 groups and administered 180360720960mg once a day The primary end point of the study was safety, and the secondary end points included pharmacokinetics, objective response rate (evaluated once every six weeks), response duration, and progression free survival < br / > the results showed that in 10 assessable NSCLC patients, 5 patients (50%) had partial remission (PR), 4 patients had stable disease (SD), and the disease control rate reached 90% (9 / 10); 5 patients with PR had been treated for 7.3-27.4 weeks when reading the data, and were still receiving treatment One of the patients who got PR continued to improve after reading the data and got complete remission (CR) at the 18th week In a total of 18 evaluable colorectal cancer patients, 13 achieved SD, and most received 180 or 360mg of the drug < br / > at the wclc2019 conference in September, amg-510, the data of phase I study, was further updated Among the 13 NSCLC patients whose curative effect can be evaluated, 7 patients had partial remission, 6 patients had stable disease, and the disease control rate was 100% The curative effect was equivalent to that before < br / > this phase I research result of amg-510 is of milestone significance, which makes the industry boiling Because it is the first clinical candidate drug for "non proprietary" target KRAS, we can see the solution to the problem of KRAS mutation tumor, such as pancreatic cancer with a mutation rate of 97% The incidence of KRAS G12C mutation in NSCLC is about 13%, in colorectal cancer is about 3% - 5%, in other solid tumors is about 1% - 2%, which is also a large market After amg-510, many KARs concept projects started to develop after amg-510 Up to now, nextpharma has included 22 KRAS related projects < br / > 4tetacep < br / > Company: Rongchang biology < br / > mechanism: TACI Fc fusion protein < br / > disease: systemic lupus erythematosus < br / > research stage: phase II / III < br / > on July 12, Rongchang biology announced the results of a key phase II / III clinical Study on the treatment of systemic lupus erythematosus (SLE) in the press release Hall of the Great Hall of the people In this study, 249 patients with SLE were enrolled in a multicenter, randomized, double-blind, placebo-controlled study The results showed that Sri (systemic lupus erythematosus response index) in the high-dose group was significantly higher than that in the placebo-controlled group (79.2% vs 32.0%) for 48 weeks, reaching the main end point of the study, with excellent safety performance and good patient tolerance < br / > based on the data of this study, Rongchang biology has submitted the listing application of thalacemide to nmpa, and it has been formally included in the priority review procedure by CDE This study is also one of the few highlight moments of innovative drugs in China Because the clinical trials of SLE are very difficult, many phase III studies abroad have failed < br / > lupus erythematosus is an autoimmune inflammatory connective tissue disease Systemic lupus erythematosus (SLE) is the most common (about 70%) and the most serious type of lupus erythematosus It occurs mostly in young women, and the age of onset is 20-40 years old The 10-year survival rate is less than 50% and gradually increases to 60% ~ 70% in recent years due to the involvement of kidney, respiratory and nervous system According to the epidemiological survey report in China, the prevalence of SLE is 70 / 100000, and the proportion of women is higher, reaching 113 / 100000 There are about one million patients in China, whose clinical needs are far from being met < br / > most of the traditional therapeutic drugs for SLE are non selective immunosuppressants, which are used to alleviate the inflammatory reaction, such as aspirin, cyclophosphamide, glucocorticoids, and hydroxychloroquine, which was approved by FDA in April 1955 Until March 9, 2011, beryluzumab for injection developed by GSK was approved by FDA to treat SLE It is the first new drug for lupus erythematosus approved in the world in nearly 60 years Since then, there has been no significant progress in this field < br / > baileyuzumab is a specific inhibitor of the first in class B lymphocyte stimulating factor (BLyS, also known as BAFF), which has a high affinity with soluble BLyS in serum, thus blocking the binding of BLyS to B cell receptor, inhibiting the proliferation of B cell and the differentiation of B cell to plasmocyte, so as to reduce the autoantibody produced by B cell in serum and achieve the purpose of treating SLE < br / > etaxel is a TACI Fc fusion protein, which can target BLyS / April two targets at the same time Compared with placebo, the improvement of Sri is significantly better than that of belimumab, and the price may be more people-friendly, which also makes everyone full of expectations for this domestic SLE new drug < br / > 5 dapagliptin < br / > Company: AstraZeneca < br / > mechanism: sglt-2 inhibitor < br / > disease: heart failure < br / > study code: dapa-hf study (phase III) < br / > on September 1, AstraZeneca announced the results of dapa-hf study in phase III of dapagliptin at the esc2019 conference This is the first outcome study in which sglt-2 inhibitors were used to treat heart failure in patients with reduced ejection fraction, whether or not accompanied by 2 diabetes mellitus It was found that dagglitazine can reduce the risk of major composite endpoints of cardiovascular death or heart failure deterioration by 26% The < br / > dapa-hf study analyzed the components of the primary composite endpoint separately The risk of the first deterioration of heart failure was reduced by 30% and the risk of death due to cardiovascular disease was reduced by 18% in the dagrinine group The effect of daggliptin on the main composite endpoints was similar in all key subgroups of the study < br / > the safety status of digressin in dapa-hf study