Recently, lilly's application to market THE CDK4/6 inhibitor Abemaciclib (the related acceptance number is JXHS1900144/145/146) has been changed to "under approval" at NMPA, which means that the second cdK4/6 inhibitor in The country is about to be approved. It is worth mentioning that Qilu Pharmaceutical a few days ago to obtain the first cdK4/6 inhibitor piperacillin imitation qualification.
Cdk4/6, or cyclin-dependent kinase 4/6, is a key regulator of the cell cycle and can trigger the cell cycle from pre-DNA synthesis (G1) to DNA replication (S1) by forming complexes with Cyclin D, phosphorylating Rb and releasing E2F. Cdk4/6 - cyclind-RB pathway is very important in ER+ breast cancer and is a key downstream target of ER signal. Once cdK4/6 kinase activity is blocked and cell cycle control is restored, the proliferation of cancer cells is blocked, thus inhibiting breast cancer growth.
Since Pfizer's Pipercilli was approved in the United States in 2015, three CDK4/6 inhibitors have been approved globally, namely Pfizer's Palbociclib (Ibrance), Novartis's Ribociclib (Kisqali) and Eli Lilly's Abemaciclib (Verzenio), with Kisqali being approved by FDA in March 2017 and Verzenio by FDA in September 2017.
Cdk4/6 inhibitors, as a rising anti-cancer "magic drug" in recent years, are rapidly changing the treatment pattern of HR+/ HER2-advanced breast cancer, effectively overcoming or delaying the emergence of endocrine resistance, and striving for more survival time for advanced patients. And, in 2020 got breast cancer diagnosis and treatment guidelines, CDK4/6 inhibitor levels by Ⅱ ascension to Ⅰ recommended level.
In China, currently only Pfizer's Piperacilli capsule was approved by NMPA in July 2018 to be used in combination with aromatase inhibitors as initial endocrine therapy for postmenopausal HR+/ HER2- locally advanced or metastatic breast cancer patients, under the trade name Iboxin. Recently, Pfizer also submitted an application for the listing of piperacillin tablets in China.
According to insight database, pp BaiXiLi capsule in domestic had approved three specifications (75 mg/grain, and 125 mg / 100 mg/grain), one of the boxes (21 grain) 75 mg of pp BaiXiLi capsule in the latest price is 20155 yuan, a box (21 grain) 100 mg of pp BaiXiLi capsule in the lowest price is 25120.47 yuan, and a box (21 grain) 125 mg of pp BaiXiLi capsule in the lowest price of 25120.47 yuan to 29799.96 yuan. According to the instructions [28 days as a cycle, once a day, once 125mg (recommended dose), continuous taking for 21 days, stop for 7 days], the new monthly treatment cost of AIBO will be at least 20,000 yuan, even without the cost of aromatase inhibitors and other therapeutic drugs and examinations, which is far beyond the affordability of the people.
Pfizer, whose patents do not expire until 2023, is in patent infringement litigation with Indian companies Aurobindo Pharma and Dr Reddy's. In China, Qilu Pharmaceutical has recently obtained the production approval of Piperacili capsule. And in April, Qilu received provisional FDA approval for its piperacillin, which is not yet available for sale because of patent issues. In addition, The Company has also submitted an application for the listing of four generic drugs for piperacilli capsules.
This time, lilly Abemaciclib's domestic listing application has entered the administrative approval stage, if officially approved, will further intensify competition in the domestic CDK4/6 inhibitor market. Bessie o according to the applications into the reasons for priority review, speculated that it will soon be approved indications are: joint fluorine d SiQun second-line treatment received endocrine therapy after disease progression of ER + / HER2 - advanced or metastatic breast cancer, and joint aromatase inhibitors as ER + / HER2 - in postmenopausal women with advanced or metastatic initial endocrine therapy of breast cancer.
In terms of indications, there is overlap between the indications of Abexin and abexili, but it is not clear who is more effective because head-to-head studies have not been done. However, in the paloma-2 study, the ORR and mPFS of the first-line treatment of postmenopausal female/male breast cancer with Aboxin combined with letrozole were 55.3% and 24.8 months respectively. Abesilie combined with non-steroidal aromatase inhibitors showed a 62.5% ORR and 28.2 months mPFS in women with breast cancer MONARCH 3 as a first-line treatment. In the future, the two CDK4/6 inhibitors are set to compete fiercely.
In addition, it is worth mentioning that abecilie is also beneficial for patients with early stage breast cancer. The monarchE interim analysis showed that, compared with standard adjuvant endocrine therapy alone, abecilie combined with standard adjuvant endocrine therapy significantly improved HR+/HER2- high risk early-stage breast cancer patients' non-invasive disease survival (IDFS) and significantly reduced the risk of disease recurrence or death. This result makes Abesilie the first and only CDK4/6 inhibitor to demonstrate improved non-invasive disease survival (IDFS) in high-risk HR+/ HER2-early breast cancer patients. If approved for early stage breast cancer in the future, Abesili will be more competitive in the market.
Currently, the three CDK inhibitors approved worldwide, Piperacili is performing well with first-mover advantage, with global sales reaching $4.961 billion in 2019. Lilly's Abesili, though the latest to go public, overtook Novartis's Kisqali in its third year. At home, Pfizer's pipercilli is now the dominant player, and with the approval of a new CDK4/6 inhibitor, its market share will no doubt be cut.
In addition to being approved for breast cancer, CDK inhibitors have also been developed for other types of cancer. In view of the huge market potential of CDK4/6 inhibitor, a number of domestic enterprises have been layout of this market. In addition to Novartis Kisqali, The SHR6390 of Hengrui Is also in phase III clinical stage, while other domestic CDK4/6 inhibitors are mostly in Phase I clinical stage.
In addition to independent research and development, Chinese enterprises have also invested heavily in foreign companies. In June, Kahe Therapeutics entered into a $46 million exclusive licensing agreement with G1 Therapeutics for the development and commercialization of cdK4/6 inhibitor Lerociclib in the Asia Pacific region, excluding Japan. In August, The company signed an exclusive licensing agreement worth up to $170 million with G1 Therapeutics inc. for the development and commercialization of all indications from its Trilaciclib, a CDK4/6 inhibitor, in the Greater China region.