Search

Background: This study aimed to evaluate the vaccine effectiveness (VE) of mRNA-1273.815, a 2023-2024 Omicron XBB.1.5-containing mRNA COVID-19 vaccine, at preventing COVID-19-related hospitalizations and any medically attended COVID-19 in adults., Methods: In a linked electronic health record-claims dataset, we identified US adults (≥18 years) who received the mRNA-1273.815 vaccine (exposed cohort) between 12 September and 15 December 2023, matched 1:1 to individuals who did not receive a 2023-2024 updated COVID-19 vaccine (unexposed cohort). Cohorts were balanced using inverse probability of treatment weighting on demographics, vaccination and infection history, and underlying medical conditions. Study cohorts were followed until 31 December 2023 for COVID-19-related hospitalizations and medically attended COVID-19. Cox regression was used to estimate hazard ratios and VE. Subgroup analyses were performed for adults ≥50 years, adults ≥65 years, and individuals with underlying medical conditions., Results: Overall, 859 335 matched pairs of mRNA-1273.815 recipients and unexposed adults were identified. The mean (standard deviation) age was 63 (16) years. More than 60% of individuals in both cohorts had an underlying medical condition. Among the overall adult population, VE was 60.2% (95% confidence interval, 53.4-66.0) against COVID-19-related hospitalization and 33.1% (30.2-35.9) against medically attended COVID-19 over a median follow-up of 63 (interquartile range: 44-78) days. VE estimates by age and underlying medical conditions were similar., Conclusions: These results demonstrate the significant protection provided by mRNA-1273.815 against COVID-19-related hospitalizations and any medically attended COVID-19 in adults, regardless of vaccination history, and support Centers for Disease Control and Prevention recommendations to stay up-to-date with COVID-19 vaccination to prevent COVID-19-related outcomes, including hospitalizations., Competing Interests: Potential conflicts of interest. A.B.A., D.M., H.K., J.A.M., M.A.M., and T.L. are employees of and shareholders in Moderna Inc. A.B., J.P.W.-J., N.Z., I.H.W., and M.B. are employees of Veradigm, which was contracted by Moderna and received fees for data management and statistical analyses. V.H.N. is an employee of VHN Consulting, which was contracted by Moderna to help conduct this analysis., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: Nemvaleukin alfa (nemvaleukin, ALKS 4230) is a novel, engineered cytokine that selectively binds to the intermediate-affinity interleukin-2 receptor, preferentially activating CD8 + T cells and natural killer cells, with minimal expansion of regulatory T cells, thereby mitigating the risk of toxicities associated with high-affinity interleukin-2 receptor activation. Clinical outcomes with nemvaleukin are unknown. ARTISTRY-1 investigated the safety, recommended phase 2 dose (RP2D), and antitumor activity of nemvaleukin in patients with advanced solid tumors., Methods: This was a three-part, open-label, phase 1/2 study: part A, dose-escalation monotherapy, part B, dose-expansion monotherapy, and part C, combination therapy with pembrolizumab. The study was conducted at 32 sites in 7 countries. Adult patients with advanced solid tumors were enrolled and received intravenous nemvaleukin once daily on days 1-5 (21-day cycle) at 0.1-10 µg/kg/day (part A), or at the RP2D (part B), or with pembrolizumab (part C). Primary endpoints were RP2D selection and dose-limiting toxicities (part A), and overall response rate (ORR) and safety (parts B and C)., Results: From July 2016 to March 2023, 243 patients were enrolled and treated (46, 74, and 166 in parts A, B, and C, respectively). The maximum tolerated dose was not reached. RP2D was determined as 6 µg/kg/day. ORR with nemvaleukin monotherapy was 10% (7/68; 95% CI 4 to 20), with seven partial responses (melanoma, n=4; renal cell carcinoma, n=3). Robust CD8 + T and natural killer cell expansion, and minimal regulatory T cell expansion were observed following nemvaleukin treatment. ORR with nemvaleukin plus pembrolizumab was 13% (19/144; 95% CI 8 to 20), with 5 complete and 14 partial responses; 6 responses were in PD-(L)1 inhibitor-approved and five in PD-(L)1 inhibitor-unapproved tumor types. Three responses were in patients with platinum-resistant ovarian cancer. The most common grade 3-4 treatment-related adverse events (TRAEs) in parts B and C, respectively, were neutropenia (49%, 21%) and anemia (10%, 11%); 4% of patients in each part discontinued due to TRAEs., Conclusions: Nemvaleukin was well tolerated and demonstrated promising antitumor activity across heavily pretreated advanced solid tumors. Phase 2/3 studies of nemvaleukin are ongoing., Trial Registration Number: NCT02799095., Competing Interests: Competing interests: UNV declares research support from Bristol Myers Squibb and Merck; consulting fees from Alkermes, Novartis, Bristol Myers Squibb, Exelixis, Bayer, Gilead, Seattle Genetics, Pfizer, and Aveo; speaker honoraria fees from Exelixis, Bayer, and Pfizer. JM declares advisory board attendance and honoraria from Exelixis. IW declares participation in advisory board for GOG Partners; Travel/Honoraria fees from Regeneron and IIT Collaborative funding from Chimerix for trial purposes only. SDR declares stock ownership at Pfizer, Amgen, and Johnson & Johnson. CJH declares grants from Merck; consulting fees from Merck, Eisai, and Seagen; honoraria fees from Eisai, Seagen, and Astellas; and advisory board attendance for CRISPR and Seagen. AChauhan declares grants from Bristol Myers Squibb, Clovis, Tersera, and ECS Progastrin; consulting fees from Tersera, Novartis, Lexicon, Ipsen, Curium, and Seneca Therapeutics; and honoraria from Tersera, Novartis, Lexicon, and Ipsen. AS declares funding to the institution from Alkermes. KDL declares funding to the institution from Alkermes and Merck; and employment with Regeneron. DSB declares independent research grant (payments made to institution) from AstraZeneca; consulting fees from or advisory board attendance for Bristol Myers Squibb, Mirati Therapeutics, Novartis, Eli Lilly, Amgen, Merck, Novocure, Regeneron, Syneos Health, Tempus and Daiichi-Sankyo; honoraria fees from AstraZeneca; advisory board attendance or travel fees from Bristol Myers Squibb, Novocure, AstraZeneca, Mirati Therapeutics and Regeneron; leadership as panel member for non-small cell lung cancer, thymic malignancies and pleural and peritoneal mesothelioma for National Comprehensive Cancer Network (NCCN). OD and MSE declare no conflicts of interest. DFM declares consulting fees from or advisory board attendance for Roche/Genentech BioOncology, Guidepoint, Bristol Myers Squibb, Merck, Exelixis, Pfizer, Lovance, Werewolf Therapeutics, and Svnthekine; leadership at Beth Israel, Dana-Farber Harvard Cancer Center; committee service at Beth Israel, Dana-Farber Harvard Cancer Center; grant review for FDA, Dana-Farber Harvard Cancer Center, National Cancer Institute; and funding from Prometheus Laboratories, X4 Pharmaceuticals, Alkermes, NIH, and Dept of Defense. JFS declares consulting fees from Synlogic (institution) and Binhui Biopharmaceuticals (institution); leadership at Dialectic Therapeutics; stock ownership at AbbVie, Abbot, Bristol Myers Squibb, Intuitive Surgical, Johnson & Johnson, Merck, and Regeneron. QSC declares grants from AstraZeneca; consulting fees from AbbVie, Amgen, AnHeart, Astellas, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Daichii Sankyo, Eli Lilly, GlaxoSmithKline, Janssen, Merck, Novartis, Ocellaris, Pfizer, Roche, and Takeda; honoraria from AbbVie, Amgen, AnHeart, Astellas, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Daichii Sankyo, Eli Lilly, GlaxoSmithKline, Janssen, Merck, Novartis, Ocellaris, Pfizer, Roche, and Takeda; serving on data and safety monitoring board for Merck KgaA; and unpaid and medical advocacy leadership for Lung Cancer Canada. LG declares consulting fees from or advisory board attendance for Merck and GlaxoSmithKline; honoraria fees from Merck, AstraZeneca, Eisai, GlaxoSmithKline, Eisai-Merck, Novocure, and GOG; institutional research funding from Merck Sharp & Dohme, IMV, AstraZeneca, ImmunoGen, Tesaro/GlaxoSmithKline, Karyopharm Therapeutics, Alkermes, OncoQuest, Novocure, Esperas Pharma, Mersana, Roche, and K-Group Beta Inc. AChaudhry declares receiving grants or clinical trial contracts from Arcus, Boehringer Ingelheim, AbbVie, Exelixis, Medilink, Gilead, Seagen, BeiGene, Roche, Tvardi, Amgen, Bristol Myers Squibb, Henlius, Merck, Mersana, Eli Lilly, Zia Pharmaceuticals, and AstraZeneca. EC declares employment at START, HM Hospitales Group; leadership at START, PharmaMar, EORTC, Sanofi, BeiGene, Novartis, and Merus NV; stock and other ownership interests at START and Oncoart Associated; honoraria fees from HM Hospitales Group; consulting or advisory role at Nanobiotix, Janssen-Cilag, Roche/Genentech, TargImmune Therapeutics, Servier, Bristol Myers Squibb, Amunix, Adcendo, Anaveon, AstraZeneca/MedImmune, Chugai Pharma, MonTa, MSD Oncology, Nouscom, Novartis, OncoDNA, T-Knife, Elevation Oncology, PharmaMar, Ellipses Pharma, Syneos Health, Genmab, and Diaccurate; research funding to the company from START; other relationships as president and founder of Foundation INTHEOS (Investigational Therapeutics in Oncological Sciences), not-for-profit foundation PharmaMar, and not-for-profit CRIS Cancer Foundation. RD declares previous employment at and stock ownership in Mural Oncology. VB declares institutional research funding from Sanofi, Seattle Genetics, Loxo, Novartis, CytomX Therapeutics, Puma Biotechnology, Kura, Tesaro, Roche/Genentech, Bristol Myers Squibb, Menarini, Synthon, Janssen Oncology, Merck, Lilly, Merus, Pfizer, Bayer, Incyte, AbbVie, Zenith Epigenetics, Genmab, AstraZeneca, Adaptimmune, Alkermes, Amgen, Array BioPharma, Boehringer Ingelheim, BioNTech AG, and Boston Biomedical; consulting fees from OncoArt, and Guidepoint Global; honoraria fees from Loxo, Ideaya Biosciences, Puma Biotechnology, Amunix, Guidepoint Global, and EMD Serono; speakers’ bureau fees from Solti, Lilly, and Tactics; advisory board attendance or travel fees from START and Bayer; leadership at Next Oncology (Institution); stock ownership at 1TRIALSP; and employment at Quironsalud, Next Oncology. VV declares serving as a consultant or in an advisory role for Bristol Myers Squibb, Merck, AstraZeneca, Regeneron, G1 Therapeutics, Amgen, GSK, and Novocure., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background/objectives: This retrospective cohort study evaluated the relative vaccine effectiveness (rVE) of two bivalent (original/Omicron BA.4/BA.5) vaccines mRNA-1273.222 versus the BNT162b2 Bivalent in preventing COVID-19-related outcomes in adults with underlying medical conditions associated with increased risk for severe COVID-19., Methods: In a linked electronic health record/claims dataset, US adults (≥18 years) with ≥1 underlying medical condition of interest who received either the bivalent vaccine between 31 August 2022 and 28 February 2023 were identified. The inverse probability of treatment weighting was used to adjust for cohort differences. Cohorts were followed up for COVID-19-related hospitalizations and outpatient encounters until 31 May 2023. Hazard ratios and rVEs were estimated using Cox regression. Subgroup analyses were performed on individuals with pre-specified comorbid conditions., Results: 757,572 mRNA-1273.222 and 1,204,975 BNT162b2 Bivalent recipients were identified. The adjusted rVE over a median follow-up of 198 days was 10.9% (6.2%-15.2%) against COVID-19-related hospitalization and 3.2% (1.7%-4.7%) against COVID-19-related outpatient encounters. rVE estimates for COVID-19 hospitalizations among subgroups with comorbid conditions were as follows: diabetes 15.1% (8.7%-21.0%), cerebro- and cardiovascular disease 14.7% (9.0%-20.1%), chronic lung disease 11.9% (5.1%-18.2%), immunocompromised 15.0% (7.2%-22.2%), chronic kidney disease 8.4% (0.5%-15.7%)., Conclusions: Overall, among adults with underlying medical conditions, mRNA-1273.222 was more effective than BNT162b2 Bivalent, especially in preventing COVID-19-related hospitalizations.