Guide : In 2021, the Center for Drug Evaluation will undertake a total of 11,569 new registration applications

Drug registration application acceptance

> > > > General situation

In 2021, the Center for Drug Evaluation will undertake a total of 11,569 new registration applications (including the combination of in vitro diagnostic reagents and medicinal devices, calculated by the acceptance number, the same below), and the number of registration applications for various types of drugs from 2016 to 2021 is shown in Figure 1

Figure 1 Number of registration applications for various types of drugs from 2016 to 2021 (unit: piece)

Note: 1.

Among them, the number of chemical drug registration applications was 8,174, an increase of 2.

Please refer to Figure 2 and Figure 3 for the application status of each product type in 2021 and the type of drug application in 2021

Figure 2 Declaration of product types in 2021 (unit: pieces)

Figure 3 Types of drug declarations in 2021 (unit: pieces)

> > > >Application of innovative drugs

In 2021, there will be a total of 1,933 new drug registration applications, including 1,756 clinical applications and 177 marketing applications

2.

> > > > Various registration applications

1.

See Figure 5 for the registration applications of various types of chemical drugs in 2021

Figure 5 Number of registration applications for various types of chemical drugs (unit: pieces)

2.

See Figure 6 for the registration applications of various types of traditional Chinese medicines in 2021

Figure 6 Number of registration applications for various types of traditional Chinese medicine (unit: piece)

3.

See Figure 7 for the registration applications for various types of biological products in 2021

Figure 7 Number of registration applications for various types of biological products (unit: piece) (The above data source: Yaodu-China Approval/Registration Database)

Review and approval of drug registration applications

In order to promote the research and development of high-quality drugs, China's "Measures for the Administration of Drug Registration" has established four accelerated drug listing procedures: special approval, breakthrough therapy drugs, conditional approval, and priority review and approval

The registration applications included in the priority review process are shown in Figure 8
.

Figure 8 Status of registration applications included in the priority review process (unit: pieces)

Note: Individual applications meet multiple priority review scopes
.

Table 1 List of drugs included in priority review in 2021

(For detailed data, scan the QR code at the bottom of the article to contact the editor for free access)

Table 2 List of priority-reviewed drugs recommended for marketing approval after partially completed reviews in 2021

> > > > Breakthrough Therapy Situations

1.
Inclusion of breakthrough therapy varieties

Breakthrough therapy drugs are used for the prevention and treatment of diseases that are seriously life-threatening or seriously affecting the quality of life, and there are no effective prevention and treatment methods or there is sufficient evidence to show that they have obvious clinical advantages compared with existing treatment methods.
Innovative drugs or improved new drugs, etc.
, are included in Drugs that have entered the "breakthrough therapy" review process will be given priority to communicate with the drug review center.
When applying for marketing, the review time limit can be shortened and application materials can be submitted on a rolling basis, and drug-related inspections and inspections will be prioritized, greatly reducing the time required for drug development to market.
time
.

According to the requirements in the "Announcement of the State Food and Drug Administration on the Release of Three Documents including the "Breakthrough Therapy Drug Review Work Procedures (Trial)" (No.
82 of 2020), the Center for Drug Evaluation in 2021 announced 50 (31 registration applications for and included in the breakthrough therapy drug program, including 17 biological drugs and 23 chemical drugs
.

Table 3 List of Breakthrough Therapy Drugs Included in 2021

(For detailed data, scan the QR code at the bottom of the article to contact the editor for free access)

> > > > Drug approvals

In 2021, there are 7,431 registration applications that have been reviewed and approved at CDE (only the review conclusions published by NMPA are counted, and other sources of review conclusions are not included)
.
There are 5,352 registration applications for chemical drugs that have completed review, including 3,361 supplementary applications, 1,101 imitations, 66 new drugs, 185 imports, 303 re-registrations for imports, 2 re-examinations, and 334 one-time imports; biological drugs have been reviewed.
There are 858 registration applications, including 591 supplementary applications, 85 new drugs, 71 imports, 48 ​​import re-registrations, and 63 one-time imports; 1,211 registration applications have been reviewed, including 1,186 supplementary applications and 10 new drugs.
, 14 were re-registered for import and 1 was re-examined
.

The review completed in 2021 is shown in Figure 9
.

Figure 9 Approved conclusions in 2021 (unit: pieces)

Note: The statistics are based on the date of issuance of the conclusions officially announced by NMPA, and the number of statistics is different when the statistical time dimension is different
.

The list (parts) of drugs approved for marketing, clinical approval and consistency evaluation in 2021 is shown in the table below
.

Table 4 List of some approved drugs in 2021

Table 5 List of some approved clinical drugs in 2021

Table 6 List of drugs that have partially passed the consistency evaluation in 2021

(The above data source: Yaodu-China Approval/Registration Database)

> > > > Overview of Approved Drug Development

In 2021, CAR-T therapy has attracted much attention due to its significant advantages in the treatment of hematological malignancies.
At present, a total of 6 CAR-T therapies have been approved for marketing in the world, 5 targeting CD19 and 1 targeting BCMA.
China 2 models were approved for listing
.

Table 7 Approved CAR-T by the end of 2021

1

Akillon Race

Achilles injection is an autologous immune cell injection developed by Cabaret Biotech and Gilead Sciences Inc.
It is an autologous targeting human CD19 chimeric antigen receptor T cell ( CAR-T) preparation
.
Fosun Kite introduced the CAR-T product Yescarta ^{® from Kite in the United States} for technology transfer and authorized localized production in China.
It is the first CAR-T drug approved for marketing in China.
It is used for the treatment of patients who have received second-line or above systemic therapy.
Adult patients with relapsed or refractory large B-cell lymphoma (including diffuse large B-cell lymphoma unspecified, primary mediastinal large B-cell lymphoma, high-grade B-cell lymphoma, and diffuse follicular lymphoma transformed diffuse large B-cell lymphoma)
.

Listing information:

On October 18, 2017, Achilles was approved by the U.
S.
Food and Drug Administration and is marketed by Kite Pharma Eu Bv under the trade name YESCARTA ^®
.
(BLA125643)

On August 23, 2018, Akiloxet was approved by the European Medicines Agency EMA and sold by Kite Pharma Eu Bv under the trade name Yescarta ^®
.
(EMEA/H/C/004480)

On January 22, 2021, Akilence was approved by the Japan Pharmaceuticals and Medical Devices Agency PMDA and sold by Daiichi Sankyo Co.
,
Ltd.

(https:// June 22, 2021, Akiloxet was approved by the NMPA of the China National Medical Products Administration (S20210019), and is sold by Fosun Kite Biotechnology Co.
, Ltd.
under the trade name ^Yikaida®
.
The injection size is about 68mL/bag, and the target dose is 2.
0×10 ^{^} 6 anti-CD19 CAR-T cells/kg body weight (acceptable range: 1.
5×10 ^{^} 6 ~ 2.
0×10 ^{^} 6 anti-CD19 CAR-T cells/ kg body weight), up to 2.
0 x 10 ^{^} 8 anti-CD19 CAR-T cells/dose
.

2

Ricky Orenza

Ruiki Orenza Injection is a chimeric antigen receptor T cell which targets CD19 like Akilenx.
Based on JCAR017, a US-based giant company, a Chinese first-class biological product is used for the treatment of adult patients with relapsed or refractory large B-cell lymphoma (r/r LBCL) after second-line or above systemic therapy
.

The approval of Rekiorenza injection was based on a single-arm, multicenter, pivotal study in China (NCT04089215), which included 59 patients with r/r LBCL who had failed at least second-line or more systemic therapy.
Adult patients, and testing these patients for up to two years and beyond, expect long-term results
.
As of December 31, 2020, among 58 patients with evaluable efficacy, the best objective response rate was 77.
6%, the best complete response rate was 51.
7%, and the 12-month OS was 76.
8%
.
During a median follow-up of 17.
9 months, among the 59 treated patients, the incidence of grade ≥3 cytokine release syndrome (CRS) and neurotoxicity (NT) were 5.
1% and 3.
4%, respectively
.
The results of long-term follow-up showed that Ruiqiorenza injection brought sustained remission and long-term survival benefits to patients, with good safety and low incidence of CAR-T-related toxicity
.

Listing information: On September 1, 2021, the drug was approved by the NMPA of the National Medical Products Administration of China (National Drug Approval No.
S20210035), sold by Shanghai WuXi Ju Nuo Biotechnology Co.
, Ltd.
, the trade name is Benoda® ^, and the injection specification Each tube is about 5mL in volume and contains no less than 25×10 ^{^} 6 CAR-T cells
.

3

Efgartigimod alfa

Efgartigimod alfa (Vyvgart ^® ) is a FCGRT antagonist developed by Argenx for the treatment of generalized myasthenia gravis (gMG) in adults with anti-acetylcholine receptor (AChR) antibody positive
.
The approval of Efgartigimod alfa was based on a 26-week, multicenter, randomized, double-blind, placebo-controlled trial (NCT03669588) of 167 patients randomized to receive VYVGART or placebo with myasthenia gravis specific daily The efficacy of VYVGART was measured by the Activities of Life Scale (MG-ADL) and Quantitative Myasthenia Gravis (QMG) scores, with higher scores indicating more severe injury
.
The primary efficacy endpoint was the comparison of the percentage of MG-ADL responders within the first treatment cycle between treatment arms in the AChR-Ab-positive population, with MG-ADL response rates of 67.
7% in the VYVGART arm versus 29.
7% in the placebo arm (p<0.
0001); the secondary endpoint was a comparison of the percentage of QMG responders in the first treatment cycle [63.
1% in the VYVGART group vs 14.
1% in the placebo group (p<0.
0001)], and the trial results demonstrated that VYVGART treatment achieved active treatment effect and with good safety
.

Listing information: On December 17, 2021, the drug was approved by the U.
S.
Food and Drug Administration (FDA) and sold by Argenx BV under the trade name Vyvgart ^® and the injection size is 400MG
.

R&D Milestones:

On October 30, 2021, a phase III clinical trial was conducted by Argenx Se for the treatment of myasthenia gravis
.
(NCT04980495)

On September 25, 2021, Vetter Pharma-Fertigung Gmbh & Co Kg, Zai Lab (Shanghai) Co.
, Ltd.
and Argenx BV launched a phase I clinical trial in mainland China for the treatment of myasthenia gravis, chronic inflammatory demyelination Polyneuropathy, thrombocytopenia, pemphigus and autoimmune diseases
.
(CTR20211952)

On September 23, 2021, Patheon Italia Spa, Zai Lab (Shanghai) Co.
, Ltd.
and Argenx BV launched a phase I clinical trial in mainland China for the treatment of myasthenia gravis, chronic inflammatory demyelinating polyneuropathy, Thrombocytopenia and pemphigus
.
(CTR20211952; CTR20211805)

On August 25, 2021, Patheon Italia Spa, Zai Lab (Shanghai) Co.
, Ltd.
and Argenx BV launched a phase III clinical trial for the treatment of pemphigus in countries such as Australia, Bulgaria and France
.
(CTR20212085; CTR20212087)

On August 25, 2021, Patheon Italia Spa, Zai Lab (Shanghai) Co.
, Ltd.
and Argenx BV launched a phase II clinical trial in Australia, Belgium and Bulgaria for the treatment of chronic inflammatory demyelinating polyneuropathy
.
(CTR20212140; CTR20212141)

On August 9, 2021, Patheon Italia Spa, Zai Lab (Shanghai) Co.
, Ltd.
and Argenx BV launched a Phase III clinical trial in mainland China for the treatment of thrombocytopenia
.
(CTR20211920; CTR20211919)

On April 14, 2021, Zai Lab (Shanghai) Co.
, Ltd.
submitted an IND application to NMPA, the National Medical Products Administration of China, for the treatment of idiopathic thrombocytopenic purpura
.
(JXSL2101009)

On February 5, 2021, Argenx Se launched a Phase III clinical trial in Spain for the treatment of myasthenia gravis
.
(NCT04818671; NCT04833894; NCT04735432)

4

Maralixibat

Maralixibat (Livmarli ^® ), a small molecule drug developed by Mirum Pharmaceuticals Inc, is an IBAT inhibitor indicated for the treatment of cholestatic pruritus in Alagille indication (ALGS) patients 1 year and older
.

The approval of Maralixibat was based on trial NCT02160782, which included an 18-week open-label treatment period (5-week dose escalation period, 13-week Livmarli 380mcg/kg once daily); 4-week randomized, double-blind, placebo-controlled discontinuation period (randomly assigned to continue Livmarli or matching placebo); a subsequent 26-week open-label treatment period (Livmarli 380mcg/kg once daily); and a long-term open-label extension period
.
A total of 31 pediatric ALGS patients with cholestasis and pruritus were included, and the median age of randomised patients was 5 years, so results reported by ItchRO [Obs] using a single observer (pruritus score 0-4 (unobserved-very high) were used.
severe)) to measure the degree of itching
.
Results showed a gradual reduction in pruritus in patients given Livmarli for 22 weeks, while patients in the placebo group who dropped out of Livmarli after Week 18 returned to baseline pruritus scores at Week 22, and after re-entering the open-label treatment phase, two weeks later at Week 28.
Mean pruritus scores were similar across the randomized treatment groups, and pruritus symptoms were significantly reduced, and these observer-assessed pruritus findings were supported by similar results from patients 5 years of age and older who were able to self-report itch severity
.

Listing information: On September 29, 2021, the drug was approved by the U.
S.
Food and Drug Administration (FDA) and sold by Mirum Pharmaceuticals Inc under the trade name Livmarli ^® , and the oral solution specification is 9.
5MG/EQ 9.
5MG BASE/ML
.

R&D Milestones:

On September 14, 2021, Mirum Pharmaceuticals Inc launched a Phase III clinical trial in Argentina and Austria for the treatment of progressive familial intrahepatic cholestasis
.
(NCT03905330)

On September 13, 2021, Mirum Pharmaceuticals Inc submitted a marketing application to the European Medicines Agency EMA for the treatment of Alagille indications .
(https://ir.
mirumpharma.
com/news-releases/news-release-details/mirum-pharmaceuticals-submits-european-marketing-authorization)

On September 09, 2021, a phase II clinical trial was conducted by Mirum Pharmaceuticals Inc in Belgium, France and Poland for the treatment of progressive familial intrahepatic cholestasis
.
(NCT04729751)

On July 12, 2021, Halo Pharmaceutical Canada Inc and Mirum Pharmaceuticals Inc conducted a Phase II clinical trial in mainland China for the treatment of biliary atresia
.
(CTR20211554)

On July 08, 2021, a phase II clinical trial was conducted by Mirum Pharmaceuticals Inc in Germany, Poland and the United Kingdom for the treatment of biliary atresia
.
(NCT04524390)

On May 24, 2021, Halo Pharmaceutical Canada Inc and Mirum Pharmaceuticals Inc launched a Phase I clinical trial in mainland China
.
(JXHL2100100; JXHL2100099; JXHL2100098; JXHL2100097)

(The above data sources: Yaodu-China Approval/Registration Database, Global Drug Database)

For more R&D milestones and investment and financing information, please refer to Pharmacodia https://data.
pharmacodia.
com

Policies and regulations

> > > > Guiding principles, policies and regulations issued by the Center for Drug Evaluation and the National Bureau in 2021

Table 8 Selected Guiding Principles for 2021

(Contact Xiaobian for free access to detailed data)

Table 9 Some policies and regulations in 2021

(Source of the above data: Yaodu-Policy and Regulation Database)
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