Post by partimefriend on Mar 19, 2020 16:45:02 GMT -5
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Edward Gane
Dose response with RNA interference (RNAi) therapy JNJ-3989 combined with nucleos(t)ide analogue (NA)
treatment in expanded cohorts of patients (pts) with chronic hepatitis B (CHB)
Edward Gane
First clinical experience with RNA interference [RNAi]-based triple combination therapy in chronic hepatitis B
(CHB): JNJ-73763989 (JNJ-3989), JNJ-56136379 (JNJ-6379) and a nucleos(t)ide analogue (NA)
www.apasl2020.org/images/APASL2020_Program_Book.pdf
www.ulabmed.com/content-134-5348-1.html
APASL2020: Triple therapy based on ARO HBV (JNJ-3989) can rapidly decrease HBsAg in some patients with chronic hepatitis B
2020-03-17 Editor: Source: Medical Connaught Medical Research: Slightly Xiao Xue
In the AROHBV1001 study, the researchers combined the RNAi therapy drug ARO HBV (now JNJ-3989) with a nucleoside (acid) analog for the treatment of chronic hepatitis B. It was observed that the combination of the two drugs had a superposition / synergy Antiviral effect and well tolerated. Therefore, researchers believe that triple therapy based on ARO HBV (JNJ-3989) may increase the functional cure rate of chronic hepatitis B after a limited course of treatment.
Professor Yuan Mengfeng and other researchers from the Mary Hospital of the University of Hong Kong in China recently published the assessment of ARO HBV (JNJ-3989) + JNJ-6379 + nucleoside (acid) analog triple therapy at the 2020 Asia Pacific Liver Disease Annual Conference (APASL2020) held in Bali, Indonesia The results of an exploratory study in chronic hepatitis B showed that patients with chronic hepatitis B were well tolerated by triple therapy, and the quantitative levels of HBsAg and other virological parameters were significantly reduced. This study is an additional cohort of the AROHBV1001 study.
Twelve patients with chronic hepatitis B received JNJ-3989 (200 mg subcutaneously, 3 doses on day 1, 29, and 57 respectively) + oral JNJ-6379 (250 mg QD) for 12 weeks and continued nucleoside ( Acid) analog treatment. Quantitative detection of HBsAg, HBeAg, HBV DNA, HBV RNA, and HBV core-associated antigen (HBcrAg) on a regular basis. The study cohort is planned to be followed up for 1 year.
The results showed that all 12 patients were Asian (median age 46 years, 8 males, including 4 HBeAg-positive and 8 HBeAg-negative patients, 7 of whom were treated with nucleoside (acid) analogs ), They all received JNJ-3989 and JNJ-6379 according to the plan, followed up for 17 to 64 days.
No deaths, discontinuation of treatment, severe / serious adverse events, or clinically significant vital signs / laboratory abnormalities were observed in the study, and 2 adverse events were reported (mild respiratory infections, irrespective of treatment).
Changes in virological parameters during treatment are shown in the figure. On days 85 and 113, HBsAg levels decreased by 1.4 ± 0.12 log IU / mL (12 patients) and 1.8 ± 0.11 log IU / mL (7 patients); all 6 patients with HBV DNA levels greater than 1000 IU / mL on day 1 All patients (3.7 to 7.7 log IU / mL) experienced rapid decline in HBV DNA.
Nine patients had quantitative results of HBV RNA (day 1.75 to 7.5 log1IU / mL); on day 29, HBV RNA in six patients fell below the lower limit of detection. HBeAg and HBcrAg levels in both HBeAg-positive (4 cases) and HBcrAg-positive (8 cases) patients decreased on day 1.
In summary, the study concluded that in the first global clinical study of RNAi-based triple regimen (ARO HBV (JNJ-3989) + JNJ-6379 + nucleoside (acid) analogues) for the treatment of chronic hepatitis B, this combination regimen was resistant to Acceptability is good, and some patients achieve a strong decline in hepatitis B surface antigen (HBsAg) and other measurable virological parameters. (For more information on new drug research on liver disease, please pay attention to the "Liver Time" WeChat public account)!
Source: 2020APASL Proceedings Abstract # 763
First clinical experience with RNA interference [RNAi] -based triple combination therapy in chronic hepatitis B (CHB): JNJ- 73763989 (JNJ-3989), JNJ-56136379 (JNJ-6379)