ABSTRACT
Introduction: The long-term benefit-risk profile of ocrelizumab (OCR) in patients (pts) with multiple sclerosis (MS) can be evaluated by regular safety reporting of clinical trial (CT) and post-marketing (PM) data. Safety/efficacy of OCR have been characterised in Phase II (NCT00676715) and Phase III (NCT01247324;NCT01412333;NCT01194570) trials and related open-label extension (OLE) periods, in relapsing-remitting MS, relapsing MS (RMS) and primary progressive MS (PPMS). It is important to understand the long-term safety profile of OCR and consider the impact of COVID-19. Aim(s): To report the continuity in safety by reporting longer-term safety evaluations from OCR CT and OLE periods over a 9-year follow-up period (up to November 2021). Method(s): Safety outcomes, with and without COVID-19, are reported for the OCR all-exposure population from 11 ongoing CTs in MS. Rates per 100 patient years (PY) are presented. Result(s): Over more than 9 years of follow-up, 5,848 pts with MS received OCR treatment in 11 CTs (25,153 PY of exposure;November 2021). Reported rates per 100 PY (95% CI) were: Adverse events (AEs), 232.71 (230.83-234.60), [excluding COVID-19 (EX COV) 230.12 (228.25-232.01)];infections, 69.89 (68.86-70.93), [EX COV 67.37 (66.36-68.39)];serious AEs, 7.61 (7.27-7.96), [EX COV 6.90 (6.58-7.23)];serious infections (SI), 2.74 (2.54-2.96), [EX COV 2.04 (1.87-2.22)];malignancies, 0.41 (0.34-0.50);SI leading to withdrawal, 0.12 (0.08-0.18), [EX COV 0.08 (0.05-0.13)];and AEs leading to discontinuation, 0.97 (0.85-1.10), [EX COV 0.93 (0.81-1.06)]. As of March 2022, over 250,000 pts with MS initiated OCR globally in the PM setting. Data remain generally consistent with those observed in CTs factoring in the impact of the COVID-19 pandemic. Conclusion(s): AE rates in the OCR all-exposure population remain generally consistent with the controlled treatment period in RMS/PPMS populations. Serious infection and malignancy rates remain within the range reported for pts with MS in realworld registries. COVID-19 did not lead to increased treatment withdrawal. Over a 9-year follow-up period, no new or unexpected safety signal was seen in pts treated with OCR in ongoing CTs. OCR continues to exhibit a stable and favourable safety profile. Regular reporting of longer-term safety data will continue.
ABSTRACT
The year 2019 witnessed a pandemic named COVID-19 caused by infection severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). It emerged in Wuhan, China, in December 2019 and has affected millions since then. It led to a global cry for vaccine development. Scientists arrayed the SARS-CoV-2 genome within a month of the outbreak. They used the parallels between SARS-CoV-1 and SARS-CoV-2 to speed up the vaccine preparation. As of now, different types of COVID-19 vaccines are prevailing. © 2022 Biomedical and Biotechnology Research Journal (BBRJ).
ABSTRACT
Severe acute respiratory syndrome coronavirus 2 and associated coronavirus disease 2019 is a newly identified human coronavirus has imposed a serious threat to global health. The rapid transmission of severe acute respiratory syndrome coronavirus 2 and its ability to spread in humans have prompted the development of new approaches for its treatment. Severe acute respiratory syndrome coronavirus 2 requires RNA-dependent RNA polymerases for life cycle propagation and Spike (S)-protein for attachment to the host cell surface receptors. The virus enters the human body with the assistance of a key functional host receptor dipeptidyl peptidase-4 primed by transmembrane serine protease 2 which are putative targets for drug development. We performed screening of 267 compounds from Curcuma longa L. (Zingiberaceae family) against the viral S-protein and RNA-dependent RNA polymerases and host receptor proteins dipeptidyl peptidase-4 and transmembrane serine protease 2 using in silico molecular docking. Compounds C1, ((4Z,6E)-1,5-dihydroxy-1,7-bis(4-hydroxy-3-methoxyphenyl)hepta-4,6-dien3-one) and C6 ((4Z,6E)-1,5-dihydroxy-1-(4-hydroxy-3-methoxyphenyl)-7-(4-hydroxyphenyl)hepta-4,6-dien-3-one) exhibited tight binding to the S1 domain of the Spike protein than VE607 and with RNA-dependent RNA polymerase protein more effectively than ribavirin and remdesivir. These compounds also interacted with the human host proteins dipeptidyl peptidase-4 and transmembrane serine protease 2 with higher efficiency than standard inhibitors sitagliptin and camostat mesylate. The lead compounds showed favorable free binding energy for all the studied protein-ligand complexes in Molecular mechanics/Generalized born model and solvent accessibility analysis. Besides, other Curcuma longa compounds C14 and C23 exhibited almost similar potential against these target proteins. The structure based optimization and molecular docking studies have provided information on some lead Curcuma longa compounds with probability for advancement in preclinical research.
ABSTRACT
Introduction: Ongoing consistent safety reporting is crucial to understand the long-term benefit-risk profile of ocrelizumab (OCR) in patients with multiple sclerosis (MS), in both clinical trials and globally, in the post-marketing (PM) setting. Safety/efficacy of OCR have been characterised in Phase II (NCT00676715) and Phase III (NCT01247324;NCT01412333;NCT01194570) trials and related open-label extension (OLE) periods, in patients with relapsing-remitting MS, relapsing MS (RMS) and primary progressive MS (PPMS). It is important to understand the longterm safety profile of OCR independent of any impact of COVID- 19 infections. Aims: To maintain continuity in the safety update by reporting longer-term safety evaluations from OCR clinical trials and OLE periods up to November 2020 and selected PM data, excluding COVID-19 cases;the latter will be communicated in a separate late-breaking abstract. Methods: Safety outcomes, excluding COVID-19, are reported for the OCR all-exposure population in Phase II/III trials and associated OLEs plus ongoing Phase IIIb trials in MS (VELOCE, CHORDS, CASTING, OBOE, ENSEMBLE, LIBERTO and CONSONANCE). To account for different exposure lengths, rates per 100 patient years (PY) are presented. The number of postmarketing OCR-treated patients is based on estimated number of vials sold and US claims data. Results: In clinical trials, 5,688 patients with MS received OCR (21,675 PY of exposure;Nov 2020). Reported rates per 100 PY (95% confidence interval) were: Adverse events (AEs), 238 (236- 240);infections, 71.8 (70.7-73.0);serious AEs, 7.05 (6.71-7.42);serious infections, 2.0 (1.82-2.20);malignancies, 0.42 (0.34- 0.52);and AEs leading to discontinuation, 0.96 (0.83-1.10). As of December 2020, over 200,000 patients with MS initiated OCR globally in the PM setting. Data remain generally consistent with those observed in clinical trials. Conclusions: AE rates in the OCR all-exposure population and PM settings, excluding COVID-19 infections, remain generally consistent with the controlled treatment period in RMS/PPMS populations. Serious infection and malignancy rates remain within the range reported for patients with MS in real-world registries. In patients with RMS and PPMS, OCR demonstrates a consistent and favourable safety profile;these longer-term data are in accordance with the safety outcomes initially observed during the controlled treatment periods. Regular reporting of longer-term safety data will continue.