Predicting Field Effectiveness of Endophytic Bacillus subtilis Inoculants for Common Bean Using Morphometric and Biochemical Markers.

According to four field experiments, after the inoculation of Phaseolus vulgaris L. cultivar Ufimskaya with the commercial strain Bacillus subtilis 26D and the promising strain B. subtilis 10-4, it was found that inoculation with B. subtilis 10-4 improved seed productivity (SP) by 31-41% per plant, but only in dry years. In contrast, all 4 years of inoculation with B. subtilis 26D were ineffective or neutral. It was intended to determine the growing and biochemical characteristics of inoculated 7-day-old plants, which correlate with the field SP of bacterial preparations. The SP of inoculated plants (average of 4 years) correlated with root length (0.83), MDA content (-0.98), and catalase (CAT) activity in roots (-0.96) of week-old seedlings. High correlation coefficients between the H2O2 content in the roots and SP (0.89 and 0.77), as well as between the H2O2 content in shoots and SP (0.98 and 0.56), were observed only in two dry years, when the influence of bacteria was detected. These physiological indicators were identified as potential markers for predicting the effectiveness of the endophytic symbiosis between bean plants and B. subtilis strains. The findings may be used to develop effective microbial-based, eco-friendly technologies for bean production.

Comparison of biosimilar Tigerase and Pulmozyme in long-term symptomatic therapy of patients with cystic fibrosis and severe pulmonary impairment (subgroup analysis of a Phase III randomized open-label clinical trial (NCT04468100)).

BACKGROUND: Patients with cystic fibrosis (CF) need costly medical care and adequate therapy with expensive medicinal products. Tigerase® is the first biosimilar of dornase alfa, developed by the lead Russian biotechnology company GENERIUM. The aim of the manuscript to present post hoc sub-analysis of patients' data with cystic fibrosis and severe pulmonary impairment of a larger comparative study (phase III open label, prospective, multi-centre, randomized study (NCT04468100)) of a generic version of recombinant human DNase Tigerase® to the only comparable drug, Pulmozyme®. METHODS: In the analyses included subgroup of 46 severe pulmonary impairment patients with baseline FEV1 level 40-60% of predicted (23 patients in each treatment group) out of 100 patients registered in the study phase III open label, prospective, multi-center, randomized study (NCT04468100), and compared efficacy endpoints (FEV1, FVC, number and time of exacerbations, body weight, St.George's Respiratory Questionnaire) as well as safety parameters (AEs, SAEs, anti-drug antibody) within 24 treatment weeks. RESULTS: All outcomes were comparable among the studied groups. In the efficacy dataset, the similar mean FEV1 and mean FVC changes for 24 weeks of both treatment groups were observed. The groups were also comparable in safety, all the secondary efficacy parameters and immunogenicity. CONCLUSIONS: The findings from this study support the clinical Tigerase® biosimilarity to Pulmozyme® administered in CF patients with severe impairment of pulmonary function.

Randomized multicenter noninferiority phase III clinical trial of the first biosimilar of eculizumab.

Currently, eculizumab is the main effective treatment for paroxysmal nocturnal hemoglobinuria (PNH). The aim of this randomized multicenter noninferiority study was to evaluate the efficacy and safety of the Biosimilar (Elizaria) in comparison with the Originator (Soliris) in patients with PNH. Biosimilar and Originator were administered at a dose of 600 mg weekly for 4 weeks at the initial stage in naive patients, as well as for maintenance therapy at a dose of 900 mg every 2 weeks in all patients. The primary endpoint was a comparative assessment of hemolytic activity based on the area under the lactate dehydrogenase (LDH) concentration-time curve during the maintenance therapy. Thirty-two (32) patients were randomized for therapy with Biosimilar (n = 16) or Originator (n = 16). The mean values of LDH concentration-time curve were similar in both treatment groups without statistically significant differences (p > 0.05). Evaluation of secondary endpoints has shown no statistically significant differences between the groups. Safety values were comparable in both treatment groups. The data obtained confirm that the Biosimilar is not inferior to the Originator in terms of the main efficacy parameter, and is also comparable with it in terms of safety and additional efficacy parameters. Clinicaltrials.gov identifier: NCT04463056.