Introduction Sotrovimab, a recombinant human monoclonal antibody (mAb) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) had US Food and Drug Administration Emergency Use Authorization for the treatment of high-risk outpatients with mild-to-moderate coronavirus disease 2019 (COVID-19) from 26 May 2021 to 5 April 2022. Real-world clinical effectiveness of sotrovimab in reducing the risk of 30-day all-cause hospitalization and/or mortality was evaluated for the period when the prevalence of circulating SARS-CoV-2 variants changed between Delta and Omicron in the USA. Methods A retrospective analysis was conducted of de-identified patients diagnosed with COVID-19 between 1 September 2021 to 30 April 2022 in the FAIR Health National Private Insurance Claims database. Patients meeting high-risk criteria were divided into two cohorts: sotrovimab and not treated with a mAb (“no mAb”). All-cause hospitalizations and facility-reported mortality ≤ 30 days of diagnosis (“30-day hospitalization or mortality”) were identified. Multivariable and propensity score-matched Poisson and logistic regressions were conducted to estimate the adjusted relative risk (RR) and odds of 30-day hospitalization or mortality in each cohort. Results Compared with the no mAb cohort ( n = 1,514,868), the sotrovimab cohort ( n = 15,633) was older and had a higher proportion of patients with high-risk conditions. In the no mAb cohort, 84,307 (5.57%) patients were hospitalized and 8167 (0.54%) deaths were identified, while in the sotrovimab cohort, 418 (2.67%) patients were hospitalized and 13 (0.08%) deaths were identified. After adjusting for potential confounders, the sotrovimab cohort had a 55% lower risk of 30-day hospitalization or mortality (RR 0.45, 95% CI 0.41–0.49) and an 85% lower risk of 30-day mortality (RR 0.15, 95% CI 0.08–0.29). Monthly, from September 2021 to April 2022, the RR reduction for 30-day hospitalization or mortality in the sotrovimab cohort was maintained, ranging from 46% to 71% compared with the no mAb cohort; the RR estimate in April 2022 was uncertain, with wide confidence intervals due to the small sample size. Conclusion Sotrovimab was associated with reduced risk of 30-day all-cause hospitalization and mortality versus no mAb treatment. Clinical effectiveness persisted during Delta and early Omicron variant waves and among all high-risk subgroups assessed. Supplementary Information The online version contains supplementary material available at 10.1007/s40121-022-00755-0.

Background Sotrovimab, a recombinant human monoclonal antibody (mAb) against SARS-CoV-2 had US FDA Emergency Use Authorization (EUA) for the treatment of high-risk outpatients with mild-to-moderate COVID-19 from May 26, 2021, to April 5, 2022. The study objective was to evaluate the real-world effectiveness of sotrovimab in reducing the risk of 30-day all-cause hospitalization and/or mortality during the time period when the prevalence of circulating SARS-CoV-2 variants was changing between Delta and Omicron sub-lineages in the US. Methods A retrospective analysis was conducted on de-identified claims data for 1,530,501 patients diagnosed with COVID-19 (ICD-10: U07.1) from September 1, 2021, to April 30, 2022, in the FAIR Health National Private Insurance Claims (FH NPIC®) database. Patients meeting EUA high-risk criteria were identified via pre-specified ICD-10-CM diagnoses in records ≤24 months prior to their first COVID-19 diagnosis and divided into two cohorts based on claimed procedural codes: treated with sotrovimab (″sotrovimab″) and not treated with a mAb (″no mAb″). All-cause hospitalizations and facility-reported all-cause mortality within 30 days of diagnosis (″30-day hospitalization or mortality″) were identified. Multivariable and propensity score-matched Poisson and logistic regressions were conducted to estimate the adjusted relative risk (RR) and odds of 30-day hospitalization or mortality among those treated with sotrovimab compared with those not treated with a mAb. Results Of the high-risk COVID-19 patients identified, 15,633 were treated with sotrovimab and 1,514,868 were not treated with a mAb. Compared with the no mAb cohort, the sotrovimab cohort was older and had a higher proportion of patients across the majority of high-risk conditions. In the no mAb cohort, 84,307 (5.57%) patients were hospitalized and 8,167 (0.54%) deaths were identified, while in the sotrovimab cohort, 418 (2.67%) patients were hospitalized and 13 (0.08%) deaths were identified. After adjusting for potential confounders, high-risk COVID-19 patients treated with sotrovimab had a 55% relative risk reduction of 30-day hospitalization or mortality (RR: 0.45, 95% CI: 0.41,0.49) and an 85% relative risk reduction of 30-day mortality (RR: 0.15, 95% CI: 0.08, 0.29) compared with high-risk patients not treated with a mAb. From September 2021 to April 2022, sotrovimab maintained clinical effectiveness with relative risk reductions of 30-day hospitalization or mortality ranging from 46% to 71%. Stratifying by high-risk condition, sotrovimab-treated patients exhibited statistically significant relative risk reductions of 30-day hospitalization or mortality compared with the no mAb cohort across all high-risk conditions (P<0.0001), ranging from 44% among pregnant women to 70% among patients 65 years and older. Conclusion In this large, US real-world, observational study of high-risk COVID-19 patients with reported diagnosis between September 2021 and April 2022 during the Delta and early Omicron variant waves, treatment with sotrovimab was associated with reduced risk of 30-day all-cause hospitalization and facility-reported mortality compared with no mAb treatment. Sotrovimab clinical effectiveness persisted throughout the months when Delta and early Omicron sub-lineages were the predominant circulating variants in the US, though there was an uncertain RR estimate in April 2022 with wide confidence intervals due to the small sample size. Sotrovimab clinical effectiveness also persisted among all high-risk subgroups assessed.

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Background: Data on effectiveness of sotrovimab preventing COVID-19-related hospitalization or mortality, particularly after the emergence of the Omicron variant, are limited. Method: Determine the real-world clinical effectiveness of sotrovimab for prevention of 30-day COVID-19 related hospitalization or mortality using a retrospective cohort within the U.S. Department of Veterans Affairs (VA) healthcare system. Veterans aged ≥18 years, diagnosed with COVID-19 between December 1, 2021, and April 4, 2022, were included. Sotrovimab recipients (n=2,816) were exactly matched to untreated controls (n=11,250) on date of diagnosis, vaccination status, and region. The primary outcome was COVID-19-related hospitalization or all-cause mortality within 30 days from diagnosis. Cox proportional hazards modeling estimated the hazard ratios (HR) and 95% Confidence Interval (CI) for the association between receipt of sotrovimab and outcomes. Results: During BA.1 dominance, compared to matched controls, sotrovimab-treated patients had a 70% lower risk hospitalization within 30 days or mortality (HR 0.30; 95%CI, 0.23-0.40), a 66% lower risk of 30-day hospitalization (HR 0.34; 95%CI, 0.25-0.46), and a 77% lower risk of 30-day all-cause mortality (HR 0.23; 95%CI, 0.14-0.38). During BA.2 dominance sotrovimab-treated patients had a 71% (HR .29; 95%CI, 0.08-0.98) lower risk of 30-day COVID-19-related- hospitalization, emergency, or urgent care. Limitations include confounding by indication. Conclusions: Using national real-world data from high risk and predominantly vaccinated Veterans, administration of sotrovimab, compared with no treatment, was associated with reduced risk of 30-day COVID-19-related hospitalization or all-cause mortality during the Omicron BA.1 period and reduced risk of progression to severe COVID-19 during the BA.2 dominant period.

Advances in personalized medicine are supported by companion diagnostic molecular tests. Testing accuracy is critical for selecting patients for optimal therapy and reducing treatment-related toxicity. We assessed the clinical and economic impact of inaccurate test results between laboratory developed tests (LDTs) and a US Food and Drug Administration (FDA)-approved test for detection of epidermal growth factor receptor (EGFR) mutations. Using a hypothetical US cohort of newly diagnosed metastatic non-small cell lung cancer (NSCLC) patients and EURTAC (erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer) clinical trial data, we developed a decision analytic model to estimate the probability of misclassification with LDTs compared to a FDA-approved test. We estimated the clinical and economic impact of inaccurate test results by quantifying progression-free and quality-adjusted progression-free life years (PFLYs, QAPFLYs) lost, and costs due to incorrect treatment. The base-case analysis estimated 2.3% (n = 1422) of 60,502 newly diagnosed metastatic NSCLC patients would be misclassified with LDTs compared to 1% (n = 577) with a FDA-approved test. An average of 477 and 194 PFLYs were lost among the misclassified patients tested with LDTs compared to the FDA-approved test, respectively. Aggregate treatment costs for patients tested with LDTs were approximately $7.3 million more than with the FDA-approved test, due to higher drug and adverse event costs among patients incorrectly treated with targeted therapy or chemotherapy, respectively. Invalid tests contributed to greater probability of patient misclassification and incorrect therapy. In conclusion, risks associated with inaccurate EGFR mutation tests pose marked clinical and economic consequences to society. Utilization of molecular diagnostic tests with demonstrated accuracy could help to maximize the potential of personalized medicine.