The three major CDK4/6 inhibitors domestic generic drugs have been approved, are the new drugs still fragrant?

Text | Zhang Hu

On February 4, 2021, the 2020 edition of WHO's Global Cancer Statistics was officially announced.

In 2018, the incidence of breast cancer and lung cancer accounted for an equal share of 11.

CDK4/6 inhibitor

The "killer weapon" in the field of breast cancer treatment

The cell division cycle (CDC) is the result of a dynamic balance between mitogenic and pro-apoptotic/stop signals, which interact in a regulatory network

Cells.

In breast cancer, hormone receptor (HR) positive and human epidermal growth factor receptor 2 (HER2) negative are the most common subtypes of breast cancer, accounting for about 60%

In the "CSCO Guidelines for Diagnosis and Treatment of Breast Cancer (2020 Edition)" and the latest version of the NCCN breast cancer guidelines, the level of evidence of CDK4/6 inhibitor combined with endocrine therapy has been upgraded from level II to level I, and it has become HR+/HER2- advanced breast cancer.

The plight of the Romance of the Three Kingdoms:

From "dominant family" to "undercurrent"

Currently, 4 CDK4/6 inhibitors have been marketed worldwide.

In terms of clinical efficacy, the three CD4/6 inhibitors are all effective treatment options for HR+/HER2- breast cancer.

In the expansion of early HR+/HER2- breast cancer indications, piperacillil and abecilil carried out phase III PALLAS and monarchE studies, respectively.

On December 31, 2020, Eli Lilly’s Abemaciclib tablet (Abemaciclib) was approved to be marketed in China, becoming the second CDK4/6 inhibitor to be listed in China after piperazil, breaking the “dominant family” of piperazil.

Data source: Insight database (http://db.

CDK4/6 melee is about to start!

The first generic drug has been approved

In view of the fact that the original patent of pibacillil will expire on January 10, 2023, many domestic pharmaceutical companies have already begun to deploy, among which Qilu Pharmaceuticals is the fastest

Details of the competition of pibacillil varieties (Insight)

Picture from: Insight database (http://db.

Generic drugs are coming fiercely, and the original research pibacillil passively counterattacks

The domestic original CDK4/6 is also actively deploying, and Hengrui is making the fastest progress

Summarize

There are many ways for innovative drugs to maintain their market competitiveness, such as developing new indications, entering medical insurance, "head-to-head" research, marketing, etc.

The entry of generic drugs and domestic innovative drugs, on the one hand, is reducing the "price" of a single product, on the other hand, it is actually "expanding the market
.
" For approved "advanced, metastatic" tumors, one of the most important means to expand the plate is to advance the medication
.
Of course, this is not something that a product can promote, and the pharmaceutical market has its own cycle
.
When a target drug can replace traditional drugs and it is found that the level of improvement in treatment advancement is higher, the guidelines may be rewritten, clinical medication may be re-guided, the drug population may be expanded, the market share multiples will increase, and the market needs to be redistributed.

.

Another important question is whether these CDK4/6 have the same efficacy in the same indication? Definitely not, it can be seen from the contradictory results of piperazil and abecilil in the treatment of early HR+/HER2- breast cancer, even if there is no head-to-head study
.
The emergence of generic drugs is inevitable.
Any kind of track will become the Red Sea in China, even if it is a pseudo track
.
And every similar drug is like a "good horse.
" Clinical trials and BE trials are like walking on a flat continent.
It feels the same.
The real decisive factor lies in clinical practice
.

[Reference material]

1.
Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F.
Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries.
CA Cancer J Clin.
2021 Feb 4 .
doi:10.
3322/caac.
21660.

2.
Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F.
Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries.
CA Cancer J Clin.
2021 May; 71(3):209-249.
doi: 10.
3322/caac.
21660.
Epub 2021 Feb 4.
PMID: 33538338.

3.
National Cancer Quality Control Center Breast Cancer Expert Committee, Chinese Anti-Cancer Association Cancer Drug Clinical Research Committee.
CDK4/6 inhibitors for the treatment of hormone receptor-positive human epidermal growth factor receptor 2 negative advanced breast cancer clinical application consensus[J ].
Chinese Journal of Oncology, 2021,43(04):405-413.

Original title: The three major CDK4/6 inhibitors had global sales of $7 billion last year! Domestic generic drugs have been approved, are new drugs still fragrant?