SAFETY AND EFFICACY OF INHALED INTERFERON-beta1A (SNG001) IN OUTPATIENTS WITH COVID-19

Background: SARS-CoV-2 variants resistant to monoclonal antibodies, and drug-drug interactions and potential mutagenicity of direct acting antivirals, heightens the need for additional therapeutics to prevent progression to severe COVID-19. Exogenous interferon beta is a promising therapeutic option against SARS-CoV-2 given its broad-spectrum antiviral activity and data suggesting impaired endogenous IFN production in individuals with severe disease. Method(s): The safety and efficacy of orally inhaled nebulized interferon-beta1a (SNG001) was evaluated in a Phase II randomized controlled trial on the ACTIV-2/ A5401 platform (NCT04518410). Adult outpatients with confirmed SARS-CoV-2 infection within 10 days of symptom onset were randomized to SNG001 once daily for 14 days or blinded pooled placebo. Primary outcomes included treatment-emergent Grade >=3 adverse event (TEAE) through day 28;time to symptom improvement of 13 targeted COVID-19 symptoms collected by daily study diary through day 28;and SARS-CoV-2 RNA < lower limit of quantification (LLoQ) from nasopharyngeal (NP) swabs at days 3, 7, and 14. All-cause hospitalization or death through day 28 was a key secondary outcome. Result(s): Of 221 participants enrolled at 25 US sites between February and August 2021, 220 (110 SNG001, 110 placebo) initiated study intervention, with a median age of 40 years, 55% female, and 20% SARS-CoV-2 vaccinated. There was no significant difference between SNG001 and placebo in Grade >=3 TEAEs (4% vs 8%, Fisher's exact test p=0.25). Median time to symptom improvement was 13 days for SNG001 and 9 days for placebo (Gehan-Wilcoxon test p=0.17). There was no difference in the proportion of participants with SARS-CoV-2 RNA < LLoQ at day 3, 7 or 14 (SNG001 vs placebo, Day 3: 28% vs. 39%;Day 7: 65% vs. 66%;Day 10: 91% vs. 91%;joint Wald test p=0.41). There were fewer hospitalizations with SNG001 (n=1;1%) compared with placebo (n=7;6%), but this difference was not statistically significant (Fisher's exact test p=0.07;Figure). All hospitalizations were due to COVID-19 and occurred among unvaccinated participants without protocol-defined high-risk factors. Conclusion(s): Inhaled nebulized SNG001 was safe and well tolerated but did not reduce SARS-CoV-2 RNA levels in the nasopharynx nor decrease time to improvement of COVID-19 symptoms in outpatients with mild-to-moderate COVID-19. The non-statistically significant decrease in hospitalizations among SNG001 participants warrants further investigation in a phase 3 clinical trial. Cumulative incidence of hospitalization or death comparing SNG001 vs. placebo.

Collection of real-world evidence of nusinersen treatment for SMA patients through a national registry: description of the paediatric cohort in the UK

Nusinersen is one of three drug treatments currently available to children and adults with spinal muscular atrophy (SMA) in England. The use of nusinersen is conditional to a managed access agreement (MAA) since July 2019. This study aims to describe the characteristics of the paediatric patients in the nusinersen MAA. Retrospective data from July 2019 to March 2022 was extracted from the SMA research and clinical hub UK (SMA REACH UK) registry which includes fifteen centres in England. Patients hold a minimum of 2 data entries yearly for each mandated field after the initial baseline assessment. The data report includes, gender, SMA type, SMN2 copy number, date of nusinersen first dose, and mandatory collection fields for medical and physiotherapy data. Medical data collection includes mortality;respiratory function (FVC and PCF, ventilation type and estimation of hours of ventilation);presence of scoliosis, spinal surgery, and Thoracolumbar support (TLSO) use and presence of fractures. The motor function measures include CHOP-INTEND, HINE, RHS, RULM and summary of contractures. 231 patients (129 males, 102 females) with SMA (Type 1=93, Type 2=85, type 3=50, pre-symptomatic=3) are receiving nusinersen via the MAA. The mean age of enrolment is 5.5 years (age range=10days-17years and 9months). There have been four deaths. During the COVID-19 pandemic structured remote assessments were agreed among the network to ensure continued collection of data, however the pandemic impacted functional outcomes collection. The SMA REACH UK registry provides a robust system to collect information on patients to address clinical uncertainties originally identified by the national institute of clinical excellence (NICE). It serves as a systematic model for longer term real-world data collection to evaluate clinical effectiveness of drugs, as well as potential evaluation of economic impact. The SMA reach UK registry has recently expanded to include adult centres. SMA reach UK is part of the international SMA registry (ISMAR) which includes registries in Italy and the US. [ FROM AUTHOR] Copyright of Neuromuscular Disorders is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

Lessons Learned: A Process Evaluation of the Rural Elder Awareness of Medication Safety (REAMS) Program.

This process evaluation of the Rural Elder Awareness of Medication Safety (REAMS) program provided identification of successful and unsuccessful elements along with barriers to and facilitators of this home-based pilot program. The REAMS program was developed to assist rural older adults aged >65 years and community health care organizations with strategies to improve health literacy related to medications. Recruitment of older adults, rurality of the program's setting, time constraints, and the onset of the COVID-19 pandemic were the greatest barriers. The collaborative relationship developed with community health care partners was the greatest facilitator. This relationship promoted shared ideas and adjustments in program design to achieve the outcome goals. The lessons learned from process evaluation may benefit future researchers or community health promotion planners with designing community-based programs for older adults in rural areas. Future research should focus on expanding recruitment opportunities in acute care, primary care, and home health with the inclusion of all established health care providers in the community. [Journal of Gerontological Nursing, 47(4), 7-12.].