Inventory of the domestic Class 1 NDA applications undertaken by CDE for the first time from January to May 2021...

Text | Drug Crazy

Five years ago, if a domestic pharmaceutical company could obtain an IND for a Class 1 new drug, it would not be an exaggeration to call it a milestone event.

1.

Table 1.

2.

01 Tigola Green Film

Tigolasheng, also LXI-15028, is a potassium ion competitive acid blocker (P-CAB), and the sponsor is Shandong Luoxin

In October 2015, Shandong Luoxin reached an agreement with CJ Health Care Corporation of South Korea to obtain the development, production and commercialization rights of Tigolasheng in China; in December 2016, Shandong Luoxin submitted a registration classification according to the classification of chemical drugs.

A multi-center, randomized, double-blind, parallel comparison of Esomeprazole in the treatment of Chinese patients with erosive esophagitis in an 8-week Phase III clinical study: a total of 261 adult Chinese patients with erosive esophagitis were enrolled in a 1:1 ratio The proportion was randomly assigned to the test group (LXI-15028 once a day, 50 mg each time) and the control group (Esomeprazole once a day, 40 mg each time).

Figure 2.

02 Befortinib mesylate capsules

Befortinib mesylate capsules, sponsored by Betta Pharmaceuticals, belong to the third-generation EGFR-TKI

The study was led by the Shanghai Chest Hospital.

As of October 2020, data show that 75-100 mg of Befortinib mesylate capsules has been used to treat locally advanced or metastatic non-small cell lung cancer patients who have developed T790M mutations after EGFR-TKI resistance.

Figure 2.

03 Dozaglietin

Dozaglietin, again Dorzagliatin (HMS5552), sponsored by Hua Medicine, is a glucokinase activator (GKA) with a new mechanism of action, designed to repair the function of the glucose sensor glucokinase (GK) in patients with type 2 diabetes , To reshape the blood glucose homeostasis of the human body, and achieve the purpose of curing type 2 diabetes

Preclinical and completed Phase III clinical studies have shown that the hypoglycemic effect in Phase II and Phase III studies is clear, with little hypoglycemia, significantly improving β cell function, and having the potential to improve GK function damaged by T2DM and improve blood glucose homeostasis

Figure 2.
3 Hua Medicine's new drug R&D pipeline

04 SHR6390 tablets

SHR6390, sponsored by Hengrui Pharmaceuticals, is an oral, highly effective and selective small molecule CDK4/6 inhibitor.
A number of clinical studies carried out by it are mainly related to the treatment of breast cancer at different stages of disease development; this variety has been included Priority review
.
In addition, there are 4 CDK4/6 inhibitors approved by the FDA for marketing, namely Pabocinil, Rebocinil, Abbecini, and Trirasinil
.

According to reports, SHR6390 has a significant inhibitory effect on the kinases CDK4 and CDK6, with IC50 close to 10 nM; IC50 for kinases CDK1 and CDK2 are both> 10000 nM, and CDK9 has an IC50> 4000 nM
.
In addition to Calu-3 cells, SHR6390 significantly inhibited the proliferation of most RB-positive tumor cell lines, but was basically ineffective against RB-negative MDA-MB-468 cells, and had limited effects on cells with low RB expression, such as SNU-182.
And OVCAR-3 cells
.
Therefore, these results show that SHR6390 has broad-spectrum anti-tumor activity against RB-positive tumor cells, and does not show obvious tissue specificity
.

According to the ASCO conference, from April 2016 to December 2018, 40 patients with advanced breast cancer were enrolled
.
MTD was not obtained during the dose-escalation phase; during the dose-expansion phase, it was expanded to 10 patients in the three dose groups of 100mg, 125mg and 150mg; 22 patients (55%) had ≥ grade 3 adverse events, including neutropenia, Leukopenia, thrombocytopenia and hypertension; no serious adverse events were observed
.
With a single administration of 50-175 mg, the drug concentration reaches its peak in 2.
5-4 hours, and then it is slowly eliminated in the body.
The plasma drug elimination half-life is 40.
3-51.
4 hours
.
The plasma concentration reached a steady state on the 8th day of continuous administration, and the Cmax and AUC0-∞ at steady state increased with the increase of the dose
.

Figure 2.
4 Recently registered clinical studies of SHR6390

05 Rezetinib Mesylate Capsules

Rezetinib mesylate, and BPI-7711, is sponsored by Shanghai Beierda Pharmaceutical Co.
, Ltd.
, which is the third-generation EGFR-TKI.
The global blockbuster variety in this direction is Osimertinib
.

In October 2019, at the 2019 North American Lung Cancer Conference organized by the International Association for Lung Cancer Research, the Phase I clinical results of BPI-7711 for the treatment of patients with EGFR/T790 mutant non-small cell lung cancer were announced
.
The purpose of this study is to determine the safety and efficacy of BPI-7711 in NSCLC patients with advanced or recurrent EGFR/T790M mutations after 1st and 2nd generation EGFR-TKI treatments.
Among 128 patients whose efficacy can be evaluated: The objective response rate (ORR) was 63.
3%; the disease control rate (DCR) was 93.
8%; in the second-phase recommended dose of 180 mg group (n=52) ORR was 73.
1% and DCR was 96.
2%; in 51 patients with brain metastases , ORR was 35.
3%, DCR was 96.
1%; in the second-phase recommended dose of 180mg group (n=52) ORR was 44%, DCR was 100%, and showed excellent therapeutic effects
.

Figure 2.
5 Shanghai Beierda's new drug R&D pipeline

06 Limpris tablets

Linperlisib, also Linperlisib (YY-20394), sponsored by Shanghai Yingli Pharmaceutical Co.
, Ltd.
, is an anti-tumor product.
It has been recognized as a breakthrough therapeutic drug in China in 2020 for the treatment of relapse and/or refractory Follicular lymphoma is the first drug product in Shanghai to be recognized as a "breakthrough therapy" drug.
According to regulations, the approval time for this product to apply for marketing authorization will be shortened from the original 200 days to 130 days
.
In addition, the product has also obtained two orphan drug qualifications issued by the FDA for indications of follicular lymphoma and chronic lymphocytic leukemia
.
As a new generation of PI3Kδ (phosphatidylinositol 3-kinase subtype δ) highly selective inhibitor developed by Yingli Pharmaceutical, the existing clinical data of Linpril has shown its good safety and significant efficacy; The effective rate for patients with relapsed and refractory follicular lymphoma is as high as 90%, and the patient only needs to be taken orally once a day, which is superior to similar marketed drugs in terms of safety, effectiveness and medication compliance
.

On March 29, 2021, Yingli Pharmaceuticals announced that its self-developed new drug Linperlisib for the treatment of relapsed/refractory follicular lymphoma phase II registration clinical trial has been completed initially.
The test results show that Linperlisib is effective in the intention-to-treat population.
Both statistical and clinical significance have been improved in terms of safety and safety
.
For example, independent data evaluation (according to the evaluation of lymphoma efficacy evaluation standard IRWG) showed that Linperlisib had an objective remission rate of more than 80% in 89 patients (evaluable cases) with relapsed/refractory follicular lymphoma, and disease control rate Up to 95% or more
.
At the same time, from the analysis of statistical results, Linperlisib oral administration is safe, controllable and well tolerated
.
Common gastrointestinal adverse reactions such as nausea and similar drugs pay special attention to the incidence of adverse reactions such as diarrhea and liver toxicity, which are lower than those reported in the literature of the same target drugs
.
Compared with traditional therapies, Linperlisib has not found vomiting, alopecia, phlebitis, cardiotoxicity and other side effects, and rarely leads to severe reduction of whole blood cells.
The medication process generally does not require hospitalization for monitoring, and it is convenient to carry, which greatly improves the life of patients.
Quality
.

Figure 2.
6 New drug R&D pipeline of Yingli Pharmaceutical

Reference materials:

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