my country's first third-generation BCR-ABL inhibitor oribatinib was launched, hitting CML resistance!

*Only for medical professionals to read or refer to Orebatinib, there is no cure for it! On December 18, the national “Major New Drug Creation” special results release and the world premiere of Orebatinib (trade name: Nerlik) sponsored by the China Association for the Promotion of Pharmaceutical Innovation and undertaken by Yasheng Pharmaceutical were held in Beijing and Suzhou.
Held simultaneously
.

Chen Kaixian, Academician of the Chinese Academy of Sciences, Song Ruilin, Executive Chairman of China Medical Innovation Promotion Association, with Professor Huang Xiaojun and Professor Jiang Qian from the Institute of Hematology, Peking University, Professor Shen Zhixiang from Ruijin Hospital Affiliated to Shanghai Jiaotong University, Professor Ma Jun from Harbin Institute of Hematology and Tumor, Soochow University Professor Wu Depei and Professor Chen Suning from the First Affiliated Hospital, Professor Hu Yu from Union Hospital of Tongji Medical College of Huazhong University of Science and Technology, Professor Niu Ting from West China Hospital of Sichuan University and many other top experts and scholars in the field of hematology and tumors gathered together to witness on-site and online Orebatinib's world premiere launch ceremony
.

It is understood that oribatinib has been approved by the National Medical Products Administration (NMPA) of China on November 25 for the treatment of resistance to any tyrosine kinase inhibitor (TKI), and uses fully validated The detection method diagnoses adult patients with chronic myeloid leukemia (CML) with T315I mutation in the chronic phase (CP) or accelerated phase (AP)
.

As the first third-generation BCR-ABL inhibitor approved for marketing in China, oribatinib will break the treatment bottleneck for patients with T315I mutation resistance in China and solve the plight of no cure
.

China’s CML drug resistance has long faced the dilemma of "no medicine to cure".
According to Professor Liu Bingcheng from the Hospital of Hematology, Chinese Academy of Medical Sciences, CML accounts for about 15% of the total adult leukemia, and the annual incidence in China is about 0.
36 per 100,000.
The annual incidence is about 1.
6~2/100,000
.

With the launch of TKI drugs targeting BCR-ABL, CML has become a clinically curable disease, and most CML patients can achieve long-term survival
.

"Therefore, although the incidence of CML is not high, the total number of patients has been quite large, and it is increasing year by year, which has brought a great disease burden to society and families
.

" In addition, Professor Liu Bingcheng pointed out that although With the first and second generation TKIs, more treatment options are available to patients, but there are still about 10% of patients who do not have an effective solution, such as those with drug resistance, especially the T315I mutation
.

Mutations in the kinase region of BCR-ABL are one of the important mechanisms of acquired drug resistance.
T315I mutation is the most common type, and the incidence rate in drug-resistant CML is as high as about 25%
.

Patients with drug-resistant CML with T315I mutation are resistant to all current first- and second-generation BCR-ABL inhibitors
.

Before oribatinib was approved for marketing, Chinese patients with T315I mutation-resistant CML faced a long-term dilemma of no cure
.

Orebatinib has significant efficacy and safety, changing the CML treatment landscape.
As the first third-generation BCR-ABL inhibitor approved for marketing in China, Orebatinib breaks the treatment bottleneck for patients with T315I mutation resistance in China.
It solves the plight of no medicine for such patients in the past
.

At this launch meeting, the main investigator of the Chinese clinical trial of Orebatinib and Professor Jiang Qian from Peking University People's Hospital shared the latest data of the drug at the meeting
.

Orebatinib-related clinical research has been selected as an oral report at the American Society of Hematology (ASH) annual meeting for four consecutive years, and the latest data on three clinical developments have been announced again at the just-convened ASH annual meeting in 2021
.

The phase I clinical study (SJ-0002) included a total of 101 CML patients, of which 83.
2% had previously received ≥2 TKI-therapies, 62.
4% had T315I mutations, and 10.
9% had compound mutations
.

The median follow-up results of 3 years showed that among CML-CP subjects, the complete hematological response (CHR) rate was 100%, and the complete cytogenetic response (CCyR) rate was 100% among the evaluable subjects who did not obtain a response at baseline.
It is 70%, and the major molecular reaction (MMR) rate is 55%
.

Among them, in patients with only the T315I mutation, the CHR rate was 100%, the CCyR rate was 84%, and the MMR rate was 78%
.

Among CML-AP subjects, among evaluable subjects who did not obtain a response at baseline, the CHR rate was 92%, the CCyR rate was 43%, and the MMR rate was 43%
.

Among them, in patients with only the T315I mutation, the CHR rate was 67%, the CCyR rate was 60%, and the MMR rate was 60%
.

In terms of safety, most of the treatment-related adverse events were grade 1 or 2
.

The results of this study show that aoribatinib is well tolerated and has a strong and sustained anti-tumor effect on TKI-resistant CML-CP or CML-AP subjects
.

"In general, with a median follow-up time of more than 3 years, oribatinib can still achieve such a high and long-lasting effective rate, especially for the T315I mutation, and the adverse reactions are reduced over time.
This is very exciting
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" Professor Jiang Qian said
.

Similarly, the latest results of the pivotal phase II trial HQP1351-CC201 study and HQP1351-CC202 study (Abstract No.
3598) show that oribatinib has a long-lasting effect in TKI-resistant CP and AP patients with T315I mutations.
The efficacy and good safety
.

In CP-CML patients who did not respond at baseline, after ≥12 treatment cycles, the CHR rate reached 100%, the major cytogenetic response (MCyR) rate was 81%, the CCyR rate was 68%, and the MMR rate was 56%; AP -CML has also achieved satisfactory clinical results, with a hematological depth response (MaHR) rate of 74%, CHR rate of 70%, MCyR rate of 52%, CCyR rate of 52%, and MMR rate of 48%
.

Prior to this, a third-generation TKI was already on the market overseas, and the U.
S.
Food and Drug Administration (FDA) issued a black box warning due to possible serious cardiovascular adverse events
.

As the original third-generation BCR-ABL inhibitor in China, once the clinical progress of oribatinib was announced, it attracted strong attention from the global hematology community
.

This fully reflects the urgency of the unmet clinical needs of CML treatment in the world
.

In addition, as a potential best-in-class new drug, data shows that its efficacy is comparable to similar products, and its safety is better
.

Professor Huang Xiaojun, the principal investigator of Chinese clinical trials, the director of the Institute of Hematology at Peking University, and the director of the Department of Hematology at Peking University People’s Hospital, said: “The effectiveness and safety data of past clinical studies continue to show us that Orebatinib is resistant to Chronic myelogenous leukemia, an unmet clinical demand field, has great potential, and it is very promising to become a'Best -in-Class' drug in this field
.

I am very happy to witness the successful launch of Oribatinib, because it means China The original drug resistance dilemma of CML treatment has been broken, and a new milestone drug has been ushered in
.
It is of great significance to clinicians and patients .

" "Our hospital also participated in the clinical trial of Orebatinib and included several cases.
Patient
.

"Professor Zhao Xielan of Xiangya Hospital of Central South University said, "CML patients may cause disease progression after drug resistance.
The T315I mutation is one of the main reasons for drug resistance, and aoribatinib can effectively overcome drug resistance.
The patient brings the opportunity to regain a new life and provides a good treatment method for clinical treatment
.

"Ingenuity advantage, oribatinib can be expected in the future.
The high-quality efficacy of oribatinib is closely related to its unique drug design and mechanism of action
.

BCR-ABL inhibitors have many drug resistance mechanisms, and different mutation sites can lead to differences.
resistance
.

the T315I mutation in the ATP binding site located on the second-generation inhibitors were resistant BCR-ABL
.

and as three generations Aolei Ba imatinib BCR-ABL inhibitors, can be competitive with ATP binding site, the current All kinase point mutations are effective, including T315I
.

Therefore, even if there is a T315I mutation, it will not affect the binding of oribatinib to BCR-ABL kinase, thereby inhibiting BCR-ABL kinase and having a clinical therapeutic effect
.

"to overcome the T315I mutation Aolei Ba is the biggest advantage of imatinib
.

And from the existing clinical data, whether or not there is a T315I mutation, oribatinib has a significant therapeutic advantage
.

"Professor Liu Bingcheng said
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As the first approved drug in the field of CML in China to choose a treatment plan based on gene mutation status, the launch of Orebatinib opened a new chapter in the precision treatment of CML
.

Authoritative guidelines at home and abroad are recommended.
CML patients should be tested for mutations in the kinase region when warning or disease progression occurs after the first/second generation TKI treatment, and the next treatment plan should be determined based on the test results
.

However, at present, many patients in the clinic often go directly to the next step of treatment through "test drugs" after drug resistance.
Due to the failure to conduct follow-up monitoring in time, or delay mutation detection, the disease has progressed when the T315I mutation is discovered, and the best treatment opportunity is missed.

.

In this regard, Professor Jiang Qian suggested that when the treatment response is unsatisfactory, and at important time points (3 months, 6 months, and 12 months), the molecular response or cellular clinical response assessment of the patient should be carried out.
Know the status of the patient
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If there are warnings and failures, genetic testing should be done
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At this listing conference, many well-known domestic hematologists discussed the scientific management of CML patients and shared their experiences and insights
.

Experts urge that regardless of the number of lines of drug resistance, CML patients should be tested for BCL-ABL mutations as soon as possible, so as not to miss the best opportunity for treatment
.

Professor Xielan Zhao said that with the renewal and iteration of BCR-ABL inhibitors, CML therapy has achieved revolutionary breakthroughs in recent years
.

With the launch of the third-generation BCR-ABL inhibitor orebatinib, the CML resistance dilemma has been broken, and a better prognosis is possible for such patients
.

In the future, I hope to further explore the long-term efficacy of Orebatinib, and hope that Orebatinib can be included in medical insurance as soon as possible to improve its accessibility
.

Based on innovation, China's innovative drug provides solutions for global CML resistance.
Orebatinib was selected as an oral report at the ASH annual meeting for four consecutive years and won the 2019 ASH Best Research Nomination Award.
Professor Huang Xiaojun believes that the most important thing is the drug Its own innovation
.

Dr.
Yifan Zhai, Chief Medical Officer of Ascent Pharmaceuticals reviewed the development process of Orebatinib.
From preclinical trials to phase I trials to phase II trials, only 11 doses were explored when the drug dose climbed.
Not easy
.

"During the development of Orebatinib, we have always adhered to international standards and the technology is leading the world.
It is the second third-generation BCR-ABL inhibitor to enter the United States clinically on a global scale.
It is also one of the few independent projects.
As for the original Chinese original innovative drug that implements the global R&D strategy
.

I hope that in the near future, Orebatinib, a Chinese original and world-leading innovative drug, can benefit more global patients
.

"In recent years, China’s new drug R&D environment Continuous improvement, the state has issued many policies to support the research and development of innovative drugs, and the approval process for new drugs has also been continuously optimized
.

In this regard, Professor Huang Xiaojun said: “Innovation is not a person’s business, but a system, a kind of thinking
.

With more and more innovations, I believe that our country will become an innovative society
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” Summary As China’s first approved listing The third-generation BCR-ABL inhibitor, oribatinib can not only change the current situation of drug-resistant patients with T315I mutation resistance in China, but also hope to fill the unsatisfied clinical gap in global CML treatment
.

In the future, I hope that the road to research on Orebatinib will be continuous, further expanding new indications and benefiting more patients
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*This article is only used to provide scientific information to medical professionals, and does not represent the views of this platform