Monthly inventory: May FDA&NMPA was approved for priority review of new drug CDE...

5，FDA7：4，Empaveli （pegcetacoplan）,Pylarify （plflufolastatF 18），FGFR2（CCA）Truseltiq （infigratinib），KRAS G12CLumakras （sotorasib）；2，Zynrelef （+），Myfembree （relugolix ++）；1，EGFR20NSCLCRybrevant （amivantamab-vmjw）。

NMPA4：，、BRCA（gBRCA）、；，，12（NMOSD）；Alkermes Pharma、Biogen，（MS）；，。

CDE priority review of 7 varieties: including Beijing Shenuoji intended to be used to treat unresectable hepatocellular carcinoma that has not received systemic treatment in the past; Hengrui intends to be used for the advancement of endocrine therapy SHR6390 tablets for recurrent or metastatic breast cancer; Genting Pharmaceuticals intends to use gosartuzumab for injection in adults with metastatic triple-negative breast cancer; Jiangsu Hausen intends to treat adults with locally advanced or metastatic non- Ametinib mesylate tablets for small cell lung cancer; Mobocertinib capsules intended for use in adults with locally advanced or metastatic NSCLC; Bayer intended for the treatment of solid tumors carrying neurotrophic tyrosine receptor kinase (NTRK) fusion genes Larotrectinib Sulfate Oral Solution/Capsule; Shanghai Yingli is intended to be used for the treatment of Linpris tablets for patients with relapsed or refractory follicular lymphoma who have received second-line or more systemic systemic treatment in the past.

One CDE breakthrough treatment variety: produced by Xinma Pharmaceutical, and intended to be used in the second-line treatment of HER2-positive advanced breast cancer with recombinant humanized anti-HER2 monoclonal antibody-AS269 conjugate (ARX788) for injection.

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7.
LUMAKRAS (SOTORASIB film)

Lumakras was developed by Amgen for the treatment of locally advanced or metastatic NSCLC with KRAS G12C mutation that has received at least one systemic treatment in the past.
Sotorasib is the world’s first drugged KRAS G12C inhibitor after more than 40 years of research on KRAS mutant oncoproteins.
It is designed to bind to KRAS G12C to lock the protein in an inactive state and prevent it from sending to drive uncontrolled cell growth.
signal.
This approval is based on the results of the CodeBreaK 100 clinical trial of 124 patients with KRAS G12C mutation-positive NSCLC who received immunotherapy and/or disease progression after chemotherapy: the total number of patients treated with Lumakras at a dose of 960 mg The response rate was 36% (95% CI: 28-45), the disease control rate reached 81% (95% CI: 73-87), and the median duration of response was 10 months.
The most common adverse reactions are diarrhea, musculoskeletal pain, nausea, fatigue, liver toxicity and cough.

2.
NMPA Approval Status

1.
Pamipali Capsules (Baihuize)

Pamidaril is a PARP inhibitor from BeiGene, which is used to treat recurrent advanced ovarian cancer, fallopian tube cancer or primary peritoneal cancer that has undergone second-line or above chemotherapy and is accompanied by gBRCA mutation.
Pamidaril is the only non-drug pump (P-gp) substrate, which is expected to overcome the problem of drug resistance caused by P-gp overexpression, and shows high selectivity for PARP1 and PARP2 enzymes.
In my country, the annual incidence of ovarian cancer ranks third among female reproductive system tumors and is increasing year by year, while the mortality rate ranks first among female reproductive tract malignant tumors.
A phase II clinical study supporting the approval of Pamiparib showed that the ORR was 64.
6%, that is, nearly two-thirds of patients had tumors that were significantly reduced, and even nearly 10% of patients had tumors completely disappeared; median remission continued The time reached 14.
5 months, indicating that the curative effect can last more than one year on average; the median progression-free survival period is 15.
2 months, and the patient's condition will not progress during this time.

2.
Saterizumab injection

Satrizizumab was developed by Roche for the treatment of AQP4 antibody-positive NMOSD in adolescents and adult patients 12 years of age and older.
NMOSD is an autoimmune disease of the central nervous system with high recurrence and high disability.
The global prevalence rate is 1.
82 per 100,000.
It mostly occurs in young adults and more women.
The incidence is higher in Asian populations.
Patients will experience unpredictable relapses, and each relapse may lead to accumulation of nerve damage and disability, resulting in severe disability consequences such as blindness and paralysis, and even death.
Satralizumab is a humanized IgG2 monoclonal antibody that targets IL-6 receptors.
By blocking IL-6 signal transduction, it regulates multiple links in the occurrence of NMOSD disease, including inhibiting the production of NMOSD specific antibody AQP4-IgG and Inflammation within and outside the central nervous system, etc.
The results of two multicenter phase III clinical studies showed that the recurrence rate of patients in the satralizumab combination therapy group was 20%, while that of the background therapy group was 43% (HR, 0.
38; 95% CI: 0.
16-0.
88); the SAkuraStar study was designed to evaluate the satralizumab alone The efficacy and safety of the drug in the treatment of patients with NMOSD, the results showed that the proportion of patients without relapse in the 48th week and 96th week of the satralizumab group was 76.
1% and 72.
1%, respectively, while that of the placebo group was 61.
9% and 51.
2%.

3.
Fampridine sustained-release tablets

Fampridine was developed by Acorda Therapeutics, and Bojian has obtained the development and commercialization rights in markets outside the United States to improve the walking ability of adult MS patients.
Fampridine sustained-release tablets is a potassium channel blocker that can enhance nerve function by improving pulse conduction across demyelinated neurons.
MS is a lifelong and progressive autoimmune disease that affects the central nervous system.
The involvement of the central nervous system gradually causes physical disabilities and impairs neurological functions such as motor, vision, and cognition.
CDE's drug review refers to three global phase 3, randomized, double-blind, placebo-controlled confirmatory studies.
The results show that the walking speed of patients treated with Fampridine Sustained-Release Tablets was significantly higher than that of the placebo group.
The release tablets have a short response time to treatment, and the efficacy is shown several weeks after the start of the treatment.

4.
Propofol Disodium Phosphate for Injection

Propofol disodium phosphate was developed by Renfu Pharmaceutical and used for intravenous induction during general anesthesia.
Propofol is an intravenous general anesthetic widely used in clinical practice.
Because of its fast onset, short half-life, high clearance rate, and convenient target-controlled infusion, it is widely used in clinical anesthesia and ICU sedation at home and abroad; but Propofol also has some adverse reactions in clinical applications, which are mainly related to the preparation of propofol with fat emulsion as a carrier.
By modifying the chemical structure of propofol and changing its dosage form, disodium phosphate propofol has good water solubility, and does not require the currently commonly used fat emulsion carrier of propofol preparations, so as to play the basis of its pharmacological effects.
To reduce the occurrence of the above-mentioned adverse reactions.
The drug was first developed by Eisai, and was withdrawn from the US market four years later due to sales reasons.
The compound patent also expired in 2019.

3.
Priority review of CDE

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Acoladine soft capsules

Beijing Shenuoji's Acoladine Soft Capsule was included in the priority review by CDE, and the proposed indication is the treatment of unresectable hepatocellular carcinoma that has not received systemic treatment in the past.
Akoladine is an immunomodulatory anti-tumor drug.
It can be directly combined with and act on the target proteins MyD88 and IKKα in the TLR/NF-kB signal transduction channel that play an important role in the immune system and the mechanism of cancer.
-6/JAK/STAT3-based inflammation and immune regulation signal pathways, which regulate multiple biological functions of tumor cells and different immune cells in the tumor immune microenvironment, including promoting tumor cell apoptosis, inhibiting tumor cell growth, and inhibiting tumors Cell stemness, inhibit the expression of inflammatory factors IL-6, IL-8, IL-10, TNF-α, and inhibit the expression of immune checkpoint PD-L1.
Hepatocellular carcinoma is a common malignant tumor with a high incidence in my country.
According to statistics, there are about 466,000 new cases and 422,000 deaths every year, which seriously threatens people's lives and health.
Previously, two phase III clinical trials of acoradine versus cinnafenib for the first-line treatment of advanced hepatocellular carcinoma were carried out; in January 2020, Sheng Nuoji announced that acoladine versus cinnafenib was the first-line treatment The interim analysis of the phase III clinical trial of the national multi-center registration of patients with advanced hepatocellular carcinoma reached the preset primary research endpoint.

2.
SHR6390 tablets

Hengrui Medicine's innovative drug SHR6390 tablets were included in the priority review by CDE.
The proposed indication is combined with Fulvestrant for hormone receptor (HR) positive and human epidermal growth factor receptor 2 (HER2) negative after endocrine therapy.
Progressive recurrent or metastatic breast cancer.
Among all breast cancer types, hormone receptor positive (luminal) accounts for about 70%; at present, endocrine therapy is the main treatment for luminal advanced breast cancer, but due to the resistance of endocrine therapy, clinical treatment often fails.
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Cell cycle-dependent protein kinase 4/6 (CDK4 and CDK6) play an important role in the regulation of the cell cycle, and CDK4 and CDK6 have therefore become important molecular targets for HR-positive metastatic breast cancer.
SHR6390 is an oral, highly effective, and selective small molecule CDK4/6 inhibitor.
The multi-center, randomized, controlled, double-blind phase III clinical study carried out before has reached the pre-specified superiority standard of the plan.
The research results show that: For patients with HR-positive and HER2-negative advanced breast cancer who have undergone endocrine therapy, SHR6390 combined with fulvestrant can significantly prolong the progression-free survival of patients compared with placebo combined with fulvestrant.

3.
Gosartorimab for injection

Genting Xinyao's Gosartuzumab for injection was included in the priority review by CDE.
The proposed indication is to treat locally unresectable advanced or metastatic triple-negative breast cancer in adults who have received at least two lines or more of previous treatment.
Triple-negative breast cancer is a highly aggressive disease, accounting for about 15% of all breast cancer types in the world; in Asia, the median age at diagnosis of breast cancer is getting younger compared with Western countries.
In the past 10 years, triple-negative breast cancer The proportion of molecular subtypes of breast cancer is gradually increasing.
The global Phase 3 ASCENT trial showed that compared with chemotherapy, the Gosartor group clinically reduced the patient’s risk of disease progression or death by 57%, and the median progression-free survival was extended from 1.
7 months to 4.
8 months (hazard ratio ( HR): 0.
43; 95% CI: 0.
35-0.
54; p<0.
0001); combined with Trodelvy, prolonged median overall survival from 6.
9 months to 11.
8 months (hazard ratio (HR): 0.
51; 95% CI : 0.
41-0.
62; p<0.
0001), reducing the risk of death by 49%.

4.
Ametinib mesylate tablets (Amelox)

The Ametinib mesylate tablets of Jiangsu Hausen were included in the priority review by CDE, and the proposed indication is the first-line treatment of local late or metastasis of epidermal growth factor receptor exon 19 deletion or exon 21 (L858R) substitution mutation in adults Sexual NSCLC.
Previously, this variety was approved for use in adult patients with locally advanced or metastatic NSCLC who have been treated with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) and have a T790M mutation.
Among lung cancer patients in my country, more than 40% are NSCLC patients.
After the first-generation EGFR-TKI treatment, more than half will develop T790M mutations and drug resistance; Ametinib is the second third-generation EGFR-TKI in the world and the world's first A third-generation EGFR-TKI with a median progression-free survival of more than 1 year (for second-line use).
The latest research results of the reported indications for marketing will be released at the 2021 American Society of Clinical Oncology (ASCO) meeting.

5.
Mobocertinib capsules

Takeda's Mobocertinib capsule was included in the priority review by CDE.
The proposed indication is for the treatment of locally advanced or metastatic NSCLC that has received chemotherapy in adults and carries an insertion mutation of EGFR exon 20.
Patients with EGFR exon 20 insertion mutations account for about 1-2% of NSCLC patients.
Compared with Western populations, this disease is more common in Asian populations.
Mobocertinib is the first oral therapy that specifically targets EGFR exon 20 insertion mutations.
The latest test data show that Mobocertinib has shown clinically significant therapeutic benefits for this type of patients, with a median overall survival of 24 months.

6.
Larotrectinib sulfate oral solution/capsules

Bayer's Larotrectinib sulfate oral solution/capsules were included in the priority review by CDE, and the proposed indication is for the treatment of adults and children with locally advanced disease, metastatic disease, or surgical resection that may cause serious complications, and those who are not satisfied with the choice of treatment options carry NTRK fusion genes Of solid tumors.
Larotrectinib is a new anti-cancer drug that targets specific gene (NTRK) mutations, not specific cancer types.
The NTRK gene fusion solid tumors that can be treated include breast cancer, colorectal cancer, lung cancer, thyroid cancer and other cancer types.
On November 27, 2018, larotrectinib (LOXO-101) was approved by the FDA for the treatment of locally advanced or metastatic solid tumors with NTRK gene fusion in adults and children.
According to the latest data released at the European Society of Medical Oncology (ESMO) annual meeting in October 2018, among 55 patients with TRK fusion tumors measured by the RECIST standard, the ORR of larotrectinib can reach 80%.
It is worth noting that the performance of larotrectinib in multiple cancer types is very consistent.

7.
Limpris tablets

Shanghai Yingli’s linpulis tablet was included in the priority review by CDE.
The proposed indication is relapsed or refractory follicular lymphoma that has previously received second-line or above systemic treatment.
Linpril is a new generation of highly selective inhibitors of phosphatidylinositol 3-kinase subtype δ (PI3Kδ), which is mainly expressed in hematopoietic cells and immune cells.
It is a key B cell receptor signal mediator, and B cell It is closely related to the survival, migration and activation of B cell, and it is a key signal molecule in the occurrence and development of B cell related autoimmune diseases and hematological malignancies.
Previously carried out a number of clinical trials in China and the United States have shown that the drug has significant efficacy and good safety; in 89 patients (evaluable cases) with relapsed/refractory follicular lymphoma, the ORR reached more than 80%.
The disease control rate (DCR) is over 95%.
At present, no PI3Kδ inhibitor has been approved for marketing in China, and Limpris tablets are expected to become the first.

4.
Breakthrough treatment varieties

Zhejiang Xinma’s recombinant humanized anti-HER2 monoclonal antibody-AS269 conjugate (ARX788) for injection was included in the list of breakthrough treatments by CDE, and the proposed indication is the second-line treatment of HER2-positive advanced breast cancer.
ARX788 is an antibody-drug conjugate (ADC), composed of anti-HER2 monoclonal antibody and toxin small molecule AS269; ARX788 binds to the cell surface HER2, enters the cell through endocytosis, is hydrolyzed in the lysosome, and releases pAF -AS269 (modified amino acid linked to toxic molecules, microtubule inhibitor); pAF-AS269 binds to tubulin, inhibits cell mitosis, induces cell cycle arrest and death.
ARX788 in the phase I clinical study of HER2-positive advanced breast cancer, the data showed significant clinical significance, the total ORR was 47.
8% (33/69), and the vast majority of adverse reactions were mild to moderate, and drug-related grade 3 The incidence of the above adverse reactions was 11.
6%, which has a significant safety advantage.