Chinese PD-(L)1 "roll" to the United States?

Author: forest

Can a clinical trial in China be approved by the US? Results will be revealed soon

In 2022, the U.

2022 FDA Approval Plan for PD-(L)1 Monoclonal Antibody

Source: evaluate

PD-(L)1 is "rolling" all over the world

According to Yaozhi data, as of January 6, 2022, the total number of global clinical trials of PD-1 target drugs has reached 3471, of which China (CDE registration) is 675, accounting for about 19.

PD-1 research accounts for 13%, 47% and 26% of the global Phase 1-3 clinical trials, respectively, and the remaining proportions are Phase 1/2, Phase 4, Phase 3/4,

Data source: Yaozhi Data

Up to now, a total of 12 PD-(L)1 products have been approved for marketing in China (8 are domestic new drugs and 4 are imported drugs)

A total of 11 PD-1 biological products have been listed in the United States, covering 7 listed varieties

Merck: Keytruda

Among all the marketed PD-(L)1 mAbs, Merck's Keytruda is the sales champion

Keytruda is the second PD-1 drug approved for marketing in the world.

In 2020, Keytruda's global sales were US$14.

In August 2021, the U.

Bristol-Myers Squibb: Opdivo

Second in sales is Bristol-Myers Squibb's Opdivo, with sales of $7.

This year, Opdivo may gain two more first-line treatment indications

The U.

Another indication, Opdivo combined with anti-CTLA-4 therapy Yervoy, Opdivo combined with chemotherapy (fluorouracil + cisplatin), first-line treatment of adult patients with unresectable advanced, recurrent or metastatic esophageal squamous cell carcinoma (ESCC), PDUFA date: May 28, 2022

4 major domestic PD-1 go to sea! Results coming soon

The most impressive words in 2021, in addition to innovation going overseas, medical insurance negotiations, etc.

At the beginning of December last year, Wanchun Pharmaceutical's Pnabrin was "dissuaded" by the FDA

Not long ago, U.
S.
FDA expert Dr.
Pazduer said at the meeting that the approval of new drugs only depends on the clinical data of one country, such as the clinical data of China, which is obviously problematic.
The principle of sex goes against the grain
.
His view was interpreted as the US FDA may tighten its review of new drugs whose clinical data come entirely from China
.

Investors can't help but worry about a number of domestic PD-(L)1 mAbs that are seeking to go overseas
.
However, the approval results will soon be known
.

Toripalimab

In February last year, Junshi Biotech and Coherus, a U.
S.
biopharmaceutical company, reached a cooperation on the development and commercialization of toripalimab in the U.
S.
and Canada
.
In March, Junshi Bio announced that it had submitted a BLA for toripalimab to the FDA for the treatment of recurrent or metastatic nasopharyngeal carcinoma
.

Toripalimab is the world's first anti-PD-1 monoclonal antibody approved for the treatment of nasopharyngeal carcinoma
.
Up to now, the US FDA has not approved any tumor immunotherapy as a treatment option for nasopharyngeal cancer, and toripalimab has been approved by the US FDA for the treatment of esophageal cancer, mucosal melanoma, nasopharyngeal cancer and soft tissue sarcoma.
Orphan drug designation, the U.
S.
FDA also granted toripalimab 2 breakthrough therapy designations, and was granted priority review in December 2021, shortening the standard 10-month review time to 6 months
.

Toripalimab adopts a "rolling application", that is, when a pharmaceutical company applies for a new drug marketing authorization, it can submit the application documents to the FDA in batches for review, instead of waiting for all the application documents to be completed before submitting the application to the FDA , which can shorten the review cycle of new drugs
.

sintilimab

Innovent is the second domestic innovative pharmaceutical company to submit a PD-1 marketing application to the FDA
.
In May 2021, the US FDA officially accepted the BLA for the new drug marketing application of sintilimab combined with pemetrexed and platinum for the first-line treatment of non-squamous non-small cell lung cancer (NSCLC)
.

Innovent Bio adopts the "normal application", which usually takes 10 months and takes longer, but because Junshi Bio has not yet completed the application, it is still in a rolling state
.
What is more clear about Innovent Bio is that the target date for the FDA to make a decision on the listing application of sintilimab is before March 2022
.

Piamprilumab

Kangfang Biologics is the third domestic company to submit a PD-1 marketing application to the FDA.
The indications for Piamprimab (AK105) to submit a BLA application to the US FDA are: third-line treatment of metastatic nasopharyngeal carcinoma
.

Pienpilimumab is the first PD-1 drug in China to undergo BLA under the FDA's RTOR (Real-Time Oncology Review) program
.

It is reported that the time required for approval of drugs participating in the RTOR program will be greatly shortened compared with the past rapid review channels, breakthrough therapies or orphan drugs, and it is the fastest channel for FDA drug review
.

Tislelizumab

In September 2021, the U.
S.
FDA accepted a New Drug Application (BLA) for tislelizumab for the treatment of patients with unresectable, recurrent locally advanced or metastatic esophageal squamous cell carcinoma (ESCC) after prior systemic therapy
.
The PDUFA target date is July 12, 2022
.

As early as January 2021, Novartis reached a cooperation and licensing agreement with BeiGene, and Novartis obtained the development, production and commercialization of tislelizumab in the United States, Canada, Mexico, the European Union, the United Kingdom, Japan and other countries.
rights, the total transaction amount reached 2.
2 billion US dollars, and the down payment received by BeiGene was as high as 650 million US dollars, setting a new historical record for the amount of down payment for Chinese new drugs "going overseas"
.
BeiGene seems to be full of confidence in going to sea this time
.

Epilogue

The PD-(L)1 track is becoming more and more crowded, the domestic "involution" is particularly serious, and the medical insurance price war is fierce, so "going overseas" is considered an important business path
.

But "going to sea" is not an easy task
.

Of the 10 "pending" accelerated approvals for PD-(L)1 mAbs since 2021, four have been voluntarily withdrawn due to low response rates
.
The remaining six were discussed at the April 2021 Oncology Drugs Advisory Committee (ODAC) meeting: three were withdrawn; one was converted to routine approval for a more limited indication; Trials and Regulatory Review
.

It can be seen that in the review of PD-(L)1, the US FDA has also increased the difficulty
.

In this domestic PD-1 "going to sea", 2022 will be an important year.
Let's wait and see when the US FDA's first listing approval will be obtained and who will get it
.

Reference source:

1.
https://