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The standard factor VIII (FVIII) prevention of hemophilia A (PwHA) is based on the patient's weight, the degree of FVIII deficiency, and bleeding, and the dosage and frequency of medication are adjusted according to the patient's clinical response.
Due to differences in the pharmacokinetics (PK) of FVIII coagulation activity in plasma, the dose of FVIII required to achieve the desired plasma FVIII level varies from person to person.
Individualized preventive treatment can improve the prognosis of patients and reduce the risk of bleeding.
The FVIII drug Rurioctocog alfa pegol has been proven to be effective in the preventive treatment of PwHA when the lowest level is ≥1%, and its safety is controllable.
However, related studies have shown that setting the FVIII level at 1% cannot effectively prevent bleeding events in all PwHA patients.
The Phase III PROPEL study explored the safety and effectiveness of Rurioctocog alfa pegol at the two lowest levels in PwHA patients.
The lowest level of 1%-3% and the lowest level of 8%-12% of Rurioctocog alfa pegol preventive treatment are effective, and the lowest level of 8%-12% of Rurioctocog alfa pegol preventive treatment makes PwHA patients less bleeding, two The lowest level of preventive treatment safety can be controlled.
Research methods The study included patients with severe PwHA (FVIII level <1%) who were 12-65 years old and had an annual bleeding rate (ABR) ≥2 within 12 months.
PwHA patients were randomly assigned to receive 12-month prophylactic treatment with Rurioctocog alfa pegol at the lowest level of 1%-3% or 8%-12% according to a 1:1 ratio.
The primary efficacy endpoint of the study is whether there is a bleeding event within 7-12 months of treatment, that is, the proportion of patients with zero bleeding.
Secondary efficacy endpoints include the proportion of patients with zero spontaneous bleeding and zero spontaneous joint bleeding within 7-12 months of treatment, ABR of joints with ≥4 spontaneous bleeding for 6 consecutive months, spontaneous ABR, ABR of spontaneous joints, and joints ABR and damage-related ABR.
Research results The study included 135 patients with PwHA, of which 115 patients with PwHA received randomization (15 patients did not receive the initial PK dose, and 5 patients discontinued the drug before randomization) received the lowest level of 1%-3% ( n=57) and 8%-12% (n=58) FVIII treatment.
All patients with PwHA included in the study were male, with a median age of 29.
0 years (range: 12-61 years).
The distribution of spontaneous bleeding in 1-3 joints ≥4 times in the two groups was similar at baseline, but the proportion of PwHA patients with spontaneous bleeding in ≥4 joints ≥4 times in the 8%-12% level group was higher.
8 patients in the 8%-12% level group discontinued (5 patients in the first 1-6 months of treatment, 1 patient in the 7-12 months of treatment), 1 patient in the 1%-3% level group discontinued the drug (7-12 months of treatment).
The overall analysis (FAS) showed that the estimated total bleeding rate of PwHA patients in the 1%-3% level group and the 8%-12% level group were 42% (95%CI: 29%-55%) and 62% ( 95%CI: 49%-75%; P=0.
055); the estimated values of the spontaneous blood rate of PwHA patients in the two groups were 60% (95%CI: 47%-72%) and 76% (95%CI: 65 %-88%; P=0.
101); The estimated values of the total bleeding rate of PwHA patients in the two groups were 65% (95%CI: 53%-77%) and 85% (95%CI: 75%-95%; P=0.
026).
The average total bleeding times of PwHA patients in the two groups were 3.
6 and 1.
6 times, respectively; the average spontaneous bleeding times were 2.
5 and 0.
7 times, respectively; the average spontaneous joint bleeding was 2.
0 and 0.
5 times, respectively.
Compared with the 12 months before PwHA enrollment, 12 months of preventive treatment with Rurioctocogalfa pegol reduced the total ABR of PwHA patients.
Among 115 patients with randomly assigned PwHA, 110 patients had a change in the number of spontaneous bleeding compared with the baseline examination.
After 6 months of preventive treatment with Rurioctocog alfa pegol, except for 1 patient in the 1%-3% level group (the other 2 patients had ≥4 spontaneous blood) and 1 patient in the 8%-12% level group (Another patient had ≥4 spontaneous blood), all patients had less joint bleeding.
A total of 204 adverse events (AEs) occurred in 70 patients (60.
9%) with PwHA in the study.
No patients with PwHA discontinued the drug due to adverse events, and no patients died due to adverse events, experienced severe thrombotic events, or developed allergic reactions.
A total of 9 serious AEs occurred in the 7 patients with PwHA in the study (1 case each for limb abscess, cellulitis, appendicitis, radius fracture, hand fracture, head injury, multiple injury, laceration, and FVIII inhibition), of which 8% One patient in the -12% level group had a serious AE related to Rurioctocog alfa pegol.
Study conclusions The study results show that increasing the minimum level of Rurioctocog alfapegol preventive treatment can increase the proportion of patients with zero-bleeding PwHA.
References: Robert Klamroth, Jerzy Windyga, Vlad Radulescu, PeterW.
Collins, et al.
Rurioctocog alfa pegol PK-guided prophylaxis in hemophiliaA: results from the phase 3 PROPEL study.
Blood(2021) 137 (13): 1818–1827.
; https://doi.
org/10.
1182/blood.
2020005673 stamp "read the original", we will make progress together
Due to differences in the pharmacokinetics (PK) of FVIII coagulation activity in plasma, the dose of FVIII required to achieve the desired plasma FVIII level varies from person to person.
Individualized preventive treatment can improve the prognosis of patients and reduce the risk of bleeding.
The FVIII drug Rurioctocog alfa pegol has been proven to be effective in the preventive treatment of PwHA when the lowest level is ≥1%, and its safety is controllable.
However, related studies have shown that setting the FVIII level at 1% cannot effectively prevent bleeding events in all PwHA patients.
The Phase III PROPEL study explored the safety and effectiveness of Rurioctocog alfa pegol at the two lowest levels in PwHA patients.
The lowest level of 1%-3% and the lowest level of 8%-12% of Rurioctocog alfa pegol preventive treatment are effective, and the lowest level of 8%-12% of Rurioctocog alfa pegol preventive treatment makes PwHA patients less bleeding, two The lowest level of preventive treatment safety can be controlled.
Research methods The study included patients with severe PwHA (FVIII level <1%) who were 12-65 years old and had an annual bleeding rate (ABR) ≥2 within 12 months.
PwHA patients were randomly assigned to receive 12-month prophylactic treatment with Rurioctocog alfa pegol at the lowest level of 1%-3% or 8%-12% according to a 1:1 ratio.
The primary efficacy endpoint of the study is whether there is a bleeding event within 7-12 months of treatment, that is, the proportion of patients with zero bleeding.
Secondary efficacy endpoints include the proportion of patients with zero spontaneous bleeding and zero spontaneous joint bleeding within 7-12 months of treatment, ABR of joints with ≥4 spontaneous bleeding for 6 consecutive months, spontaneous ABR, ABR of spontaneous joints, and joints ABR and damage-related ABR.
Research results The study included 135 patients with PwHA, of which 115 patients with PwHA received randomization (15 patients did not receive the initial PK dose, and 5 patients discontinued the drug before randomization) received the lowest level of 1%-3% ( n=57) and 8%-12% (n=58) FVIII treatment.
All patients with PwHA included in the study were male, with a median age of 29.
0 years (range: 12-61 years).
The distribution of spontaneous bleeding in 1-3 joints ≥4 times in the two groups was similar at baseline, but the proportion of PwHA patients with spontaneous bleeding in ≥4 joints ≥4 times in the 8%-12% level group was higher.
8 patients in the 8%-12% level group discontinued (5 patients in the first 1-6 months of treatment, 1 patient in the 7-12 months of treatment), 1 patient in the 1%-3% level group discontinued the drug (7-12 months of treatment).
The overall analysis (FAS) showed that the estimated total bleeding rate of PwHA patients in the 1%-3% level group and the 8%-12% level group were 42% (95%CI: 29%-55%) and 62% ( 95%CI: 49%-75%; P=0.
055); the estimated values of the spontaneous blood rate of PwHA patients in the two groups were 60% (95%CI: 47%-72%) and 76% (95%CI: 65 %-88%; P=0.
101); The estimated values of the total bleeding rate of PwHA patients in the two groups were 65% (95%CI: 53%-77%) and 85% (95%CI: 75%-95%; P=0.
026).
The average total bleeding times of PwHA patients in the two groups were 3.
6 and 1.
6 times, respectively; the average spontaneous bleeding times were 2.
5 and 0.
7 times, respectively; the average spontaneous joint bleeding was 2.
0 and 0.
5 times, respectively.
Compared with the 12 months before PwHA enrollment, 12 months of preventive treatment with Rurioctocogalfa pegol reduced the total ABR of PwHA patients.
Among 115 patients with randomly assigned PwHA, 110 patients had a change in the number of spontaneous bleeding compared with the baseline examination.
After 6 months of preventive treatment with Rurioctocog alfa pegol, except for 1 patient in the 1%-3% level group (the other 2 patients had ≥4 spontaneous blood) and 1 patient in the 8%-12% level group (Another patient had ≥4 spontaneous blood), all patients had less joint bleeding.
A total of 204 adverse events (AEs) occurred in 70 patients (60.
9%) with PwHA in the study.
No patients with PwHA discontinued the drug due to adverse events, and no patients died due to adverse events, experienced severe thrombotic events, or developed allergic reactions.
A total of 9 serious AEs occurred in the 7 patients with PwHA in the study (1 case each for limb abscess, cellulitis, appendicitis, radius fracture, hand fracture, head injury, multiple injury, laceration, and FVIII inhibition), of which 8% One patient in the -12% level group had a serious AE related to Rurioctocog alfa pegol.
Study conclusions The study results show that increasing the minimum level of Rurioctocog alfapegol preventive treatment can increase the proportion of patients with zero-bleeding PwHA.
References: Robert Klamroth, Jerzy Windyga, Vlad Radulescu, PeterW.
Collins, et al.
Rurioctocog alfa pegol PK-guided prophylaxis in hemophiliaA: results from the phase 3 PROPEL study.
Blood(2021) 137 (13): 1818–1827.
; https://doi.
org/10.
1182/blood.
2020005673 stamp "read the original", we will make progress together
