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The introductory phrase "The southern country is more gorgeous,
and the sea is beautiful.
" On January 9, 2021, the 2021 Urogenital Tumor Xintiandi Forum and Enzalutamide Non-metastatic Castration-Resistant Prostate Cancer (nmCRPC) China Listing Conference will be held on January 9, 2021.
Zhuhai was successfully held.
In November 2020, the National Medical Products Administration (NMPA) of China approved enzalutamide for the treatment of nmCRPC, which is the second indication for enzalutamide approved in China.
Previously, the drug has been approved for the treatment of adult patients with metastatic castration-resistant prostate cancer (mCRPC).
From mCRPC to nmCRPC, the indications of enzalutamide continue to move forward, becoming a new "weapon" for urological oncologists to treat advanced prostate cancer.
At this listing conference, Professor Wei Qiang from West China Hospital of Sichuan University and Professor Bertrand Tombal from St.
Luke University Clinic in Belgium made wonderful sharing of the development process and clinical data of enzalutamide.
The development process of a new generation of androgen receptor (AR) inhibitor drugs Professor Wei Qiang said that the development process of enzalutamide is unique, from the first in vitro test to the approval of the U.
S.
Food and Drug Administration (FDA), which lasted 7 year.
Figure 1 Enzalutamide research and development process In the first in vitro test in 2005, Enzalutamide (MDV3100) stood out from more than 200 molecules, and was designed to target the AR signal pathway to give it a new mechanism of action, direct and potent Inhibit the three key stages of the AR signaling pathway: inhibit the binding of androgens to AR, inhibit AR nuclear translocation, and inhibit AR-mediated DNA binding.
A preclinical competitive test measured the relative AR affinity of enzalutamide, bicalutamide, and a control ligand (FDHT).
The results showed that the relative affinity of enzalutamide to AR binding in a preclinical CRPC model It is 5 to 8 times that of bicalutamide.In an open, uncontrolled, dose-escalating phase I to II study (S-3100-1-01) evaluating enzalutamide in patients with progressive CRPC, enzalutamide has achieved encouraging anti- Tumor activity has promoted the clinical research and development process.
At the same time, it has been determined that the optimal dose of enzalutamide is 160 mg/day, and the maximum tolerated dose is 240 mg/day.
Professor Wei introduced the overall layout of enzalutamide in advanced prostate cancer, from the AFFIRM, PREVALIL, and Asian PREVAIL studies at the mCRPC stage, to the PROSPER study at nmCRPC, and the TERRAIN study compared with bicalutamide head-to-head.
The EMBARK studies of ARCHES, China ARCHES, and high-risk M0 BCR, which are advanced to the stage of metastatic hormone-sensitive prostate cancer (mHSPC), show us the prospect of drug development for enzalutamide.
Professor Wei finally stated that the current treatment options for male patients with advanced prostate cancer in China are limited, and the continuous exploration of enzalutamide provides new clinical options.
The approval of the indication for enzalutamide nmCRPC marks a major progress in this devastating disease, and provides a new and meaningful treatment option for doctors and patients with castration-resistant prostate cancer (CRPC).
From PROSPER to PREVALIL, enzalutamide clinical research data and practice frontier Professor Bertrand Tombal shared 1 asymptomatic mCRPC case and 1 nmCRPC case, and introduced us the good benefits of enzalutamide PERVAIL and PROSPER research.
01 case 1 Figure 2 mCRPC case The patient started to receive degarelix and 6 cycles of docetaxel treatment, and was asymptomatic; after that, the PSA rose rapidly and remained asymptomatic.
The whole body MRI showed 2 bone metastases.
It was judged that the patient entered the mCRPC stage.
The EAU guidelines define CRPC as: (1) Serum testosterone is at castrated level: <50ng/dl or 1.
7nmol/L; (2) One of the following two conditions is met: PSA progress: PSA> 2ng/ml, PSA increased three times in a row at an interval of one week, and the two increased by more than 50% compared to the lowest point; imaging progress: bone scan revealed ≥2 new bone lesions; CT or MR suggested soft tissue lesion progress (RECISIT 1.
1).
Professor Bertrand Tombal said that enzalutamide or abiraterone has changed the pattern of mCRPC treatment.
The results of the PREVAIL and COU-AA-302 studies show that the first-line treatment of enzalutamide and abiraterone in mCRPC patients can significantly improve progression-free survival (PFS) and overall survival (OS).
The PREVAIL study showed that compared with the placebo group, enzalutamide prolonged OS by 5 months (36 vs 31 months; HR, 0.
83; 95% CI: 0.
75-0.
93).
Therefore, it is better to immediately use Androgen Receptor Targeted Therapy (ARTA) for patients who are still asymptomatic and low tumor burden, and early use of enzalutamide can help maintain a good quality of life for patients.
Based on the strong support of the above two studies, in the St.
Gallen Advanced Prostate Cancer Consensus Conference (APCCC), for the first-line treatment of asymptomatic mCRPC patients whether receiving docetaxel treatment or not, the vast majority of experts recommended Enzalu Amine or abiraterone.
In view of the good safety and convenience of enzalutamide, mCRPC patients with diabetes mellitus, cardiac ejection fraction lower than 45-50% or active liver dysfunction who require prescription drug treatment are more inclined to sequential treatment For choosing enzalutamide.
Figure 3 PREVAIL study OS results 02 case 2 Figure 4 nmCRPC case Professor Bertrand Tombal said that this case is a nmCRPC patient.
Based on the excellent results of the SPARTAN, ARAMIS, and PROSPER studies, the EAU guidelines recommend apatamide, dalotamide or enzymatic Zalutamide treats mCRPC patients with high risk of metastasis (PSADT <10 months) to extend the time to metastasis. Figure 5 The PROSPER study recommended by the EAU guidelines showed that compared with the placebo group, enzalutamide can significantly prolong the metastasis-free survival of patients with high-risk nmCRPC (MFS, 36.
6 vs 14.
7 months; HR, 0.
29; 95% CI, 0.
24- 0.
35), OS (67.
0 vs 56.
3 months; HR, 0.
73; 95% CI, 0.
61-0.
89), time to PSA progression (37.
2 vs 3.
9 months; HR, 0.
07; 95% CI, 0.
05-0.
08), to imaging The time to study progress and the time to the use of new anti-tumor treatments, and can delay the deterioration of urinary and intestinal symptoms.
At the same time, enzalutamide is safe and has a low incidence of adverse events, which has established enzalutamide as the first-line treatment for nmCRPC.
Figure 6 PROSPER study MFS results Figure 7 PROSPER study OS results The approval of the indication for enzalutamide nmCRPC means that enzalutamide has achieved full coverage of the CRPC population.
While foreign countries have approved enzalutamide for the treatment of mHSPC, domestic trials are currently being carried out in an orderly manner.
In the future, we look forward to the approval of more indications for enzalutamide in China, which will benefit more and more patients.
Source: "Tanbi Xintiandi" WeChat public account
and the sea is beautiful.
" On January 9, 2021, the 2021 Urogenital Tumor Xintiandi Forum and Enzalutamide Non-metastatic Castration-Resistant Prostate Cancer (nmCRPC) China Listing Conference will be held on January 9, 2021.
Zhuhai was successfully held.
In November 2020, the National Medical Products Administration (NMPA) of China approved enzalutamide for the treatment of nmCRPC, which is the second indication for enzalutamide approved in China.
Previously, the drug has been approved for the treatment of adult patients with metastatic castration-resistant prostate cancer (mCRPC).
From mCRPC to nmCRPC, the indications of enzalutamide continue to move forward, becoming a new "weapon" for urological oncologists to treat advanced prostate cancer.
At this listing conference, Professor Wei Qiang from West China Hospital of Sichuan University and Professor Bertrand Tombal from St.
Luke University Clinic in Belgium made wonderful sharing of the development process and clinical data of enzalutamide.
The development process of a new generation of androgen receptor (AR) inhibitor drugs Professor Wei Qiang said that the development process of enzalutamide is unique, from the first in vitro test to the approval of the U.
S.
Food and Drug Administration (FDA), which lasted 7 year.
Figure 1 Enzalutamide research and development process In the first in vitro test in 2005, Enzalutamide (MDV3100) stood out from more than 200 molecules, and was designed to target the AR signal pathway to give it a new mechanism of action, direct and potent Inhibit the three key stages of the AR signaling pathway: inhibit the binding of androgens to AR, inhibit AR nuclear translocation, and inhibit AR-mediated DNA binding.
A preclinical competitive test measured the relative AR affinity of enzalutamide, bicalutamide, and a control ligand (FDHT).
The results showed that the relative affinity of enzalutamide to AR binding in a preclinical CRPC model It is 5 to 8 times that of bicalutamide.In an open, uncontrolled, dose-escalating phase I to II study (S-3100-1-01) evaluating enzalutamide in patients with progressive CRPC, enzalutamide has achieved encouraging anti- Tumor activity has promoted the clinical research and development process.
At the same time, it has been determined that the optimal dose of enzalutamide is 160 mg/day, and the maximum tolerated dose is 240 mg/day.
Professor Wei introduced the overall layout of enzalutamide in advanced prostate cancer, from the AFFIRM, PREVALIL, and Asian PREVAIL studies at the mCRPC stage, to the PROSPER study at nmCRPC, and the TERRAIN study compared with bicalutamide head-to-head.
The EMBARK studies of ARCHES, China ARCHES, and high-risk M0 BCR, which are advanced to the stage of metastatic hormone-sensitive prostate cancer (mHSPC), show us the prospect of drug development for enzalutamide.
Professor Wei finally stated that the current treatment options for male patients with advanced prostate cancer in China are limited, and the continuous exploration of enzalutamide provides new clinical options.
The approval of the indication for enzalutamide nmCRPC marks a major progress in this devastating disease, and provides a new and meaningful treatment option for doctors and patients with castration-resistant prostate cancer (CRPC).
From PROSPER to PREVALIL, enzalutamide clinical research data and practice frontier Professor Bertrand Tombal shared 1 asymptomatic mCRPC case and 1 nmCRPC case, and introduced us the good benefits of enzalutamide PERVAIL and PROSPER research.
01 case 1 Figure 2 mCRPC case The patient started to receive degarelix and 6 cycles of docetaxel treatment, and was asymptomatic; after that, the PSA rose rapidly and remained asymptomatic.
The whole body MRI showed 2 bone metastases.
It was judged that the patient entered the mCRPC stage.
The EAU guidelines define CRPC as: (1) Serum testosterone is at castrated level: <50ng/dl or 1.
7nmol/L; (2) One of the following two conditions is met: PSA progress: PSA> 2ng/ml, PSA increased three times in a row at an interval of one week, and the two increased by more than 50% compared to the lowest point; imaging progress: bone scan revealed ≥2 new bone lesions; CT or MR suggested soft tissue lesion progress (RECISIT 1.
1).
Professor Bertrand Tombal said that enzalutamide or abiraterone has changed the pattern of mCRPC treatment.
The results of the PREVAIL and COU-AA-302 studies show that the first-line treatment of enzalutamide and abiraterone in mCRPC patients can significantly improve progression-free survival (PFS) and overall survival (OS).
The PREVAIL study showed that compared with the placebo group, enzalutamide prolonged OS by 5 months (36 vs 31 months; HR, 0.
83; 95% CI: 0.
75-0.
93).
Therefore, it is better to immediately use Androgen Receptor Targeted Therapy (ARTA) for patients who are still asymptomatic and low tumor burden, and early use of enzalutamide can help maintain a good quality of life for patients.
Based on the strong support of the above two studies, in the St.
Gallen Advanced Prostate Cancer Consensus Conference (APCCC), for the first-line treatment of asymptomatic mCRPC patients whether receiving docetaxel treatment or not, the vast majority of experts recommended Enzalu Amine or abiraterone.
In view of the good safety and convenience of enzalutamide, mCRPC patients with diabetes mellitus, cardiac ejection fraction lower than 45-50% or active liver dysfunction who require prescription drug treatment are more inclined to sequential treatment For choosing enzalutamide.
Figure 3 PREVAIL study OS results 02 case 2 Figure 4 nmCRPC case Professor Bertrand Tombal said that this case is a nmCRPC patient.
Based on the excellent results of the SPARTAN, ARAMIS, and PROSPER studies, the EAU guidelines recommend apatamide, dalotamide or enzymatic Zalutamide treats mCRPC patients with high risk of metastasis (PSADT <10 months) to extend the time to metastasis. Figure 5 The PROSPER study recommended by the EAU guidelines showed that compared with the placebo group, enzalutamide can significantly prolong the metastasis-free survival of patients with high-risk nmCRPC (MFS, 36.
6 vs 14.
7 months; HR, 0.
29; 95% CI, 0.
24- 0.
35), OS (67.
0 vs 56.
3 months; HR, 0.
73; 95% CI, 0.
61-0.
89), time to PSA progression (37.
2 vs 3.
9 months; HR, 0.
07; 95% CI, 0.
05-0.
08), to imaging The time to study progress and the time to the use of new anti-tumor treatments, and can delay the deterioration of urinary and intestinal symptoms.
At the same time, enzalutamide is safe and has a low incidence of adverse events, which has established enzalutamide as the first-line treatment for nmCRPC.
Figure 6 PROSPER study MFS results Figure 7 PROSPER study OS results The approval of the indication for enzalutamide nmCRPC means that enzalutamide has achieved full coverage of the CRPC population.
While foreign countries have approved enzalutamide for the treatment of mHSPC, domestic trials are currently being carried out in an orderly manner.
In the future, we look forward to the approval of more indications for enzalutamide in China, which will benefit more and more patients.
Source: "Tanbi Xintiandi" WeChat public account
