Content ...... 3 1 Background: policy question and methods ...... 7 1.1 Policy Question ...... 7 1.2 Methodology ...... 7 1.3 Selection of Products for “Vignettes” ...... 10 2 Results: Vaccines ...... 11 2.1 Moderna Therapeutics—US National Institute of Allergy ...... 16 2.2 University of Oxford/ Astra Zeneca ...... 18 2.3 BioNTech/Fosun Pharma/Pfizer ...... 20 2.4 Janssen Pharmaceutical/ Johnson & Johnson ...... 22 2.5 Novavax ...... 23 2.6 CureVac ...... 24 2.7 Sanofi and GSK ...... 26 3 Results: Therapeutics ...... 28 3.1 (Veklury®) ...... 33 3.2 Lopinavir + (Kaletra®) ...... 42 3.3 (Avigan®) ...... 42 3.4 Darunavir ...... 51 3.5 Chloroquine (Resochin®) and ...... 53 3.6 Hydroxychloroquine (Plaquenil®) ...... 53 3.7 Camostat Mesilate (Foipan®) ...... 53 3.8 APN01/ Recombinant Human Angiotensin-converting Enzyme 2 (rhACE2) ...... 54 3.9 Tocilizumab (Roactemra®) ...... 54 3.10 Sarilumab (Kevzara®) ...... 60 3.11 beta 1a (SNG001) (Rebif®, Avonex®) and Interferon beta 1b (Betaferon®, Extavia®) ...... 61 3.12 Convalescent plasma transfusion ...... 65 3.13 Plasma derived medicinal products ...... 71 3.13.1 REGN-COV2 - combination of two monoclonal antibodies (REGN10933 and REGN10987) ...... 71 3.13.2 LY-CoV555 - neutralizing IgG1 monoclonal antibody (bamlanivimab) and LY-CoV016 - recombinant fully human monoclonal neutralizing antibody (etesevimab) ...... 74 3.13.3 AZD7442 - combination of two monoclonal antibodies (AZD8895 + AZD1061) ...... 82 3.13.4. VIR-7831 monoclonal antibody ...... 82 3.14 Combination therapy – triple combination of interferon beta-1b, lopinavir–ritonavir and vs. lopinavir–ritonavir or other triple combination of ...... 83 3.15 Solnatide ...... 89 3.16 (Arbidol®) ...... 90 3.17 Dexamethasone and other corticosteroids ...... 94 3.18 Anakinra (Kineret®) ...... 99 3.19 Colchicine ...... 103 3.20 Nafamostat (Futhan©) ...... 106 3.21 Gimsilumab ...... 106 3.22 Canakinumab ...... 107 3.23 Lenzilumab ...... 107 3.24 Vitamin D ...... 108 3.25 Baricitinib ...... 111 3.26 Molnupiravir ...... 114 3.27 Ivermectin ...... 114

3.28 Aspirin (acetylsalicylic acid)...... 117 References ...... 119

Figure 1.2-1: A living mapping of ongoing randomized trials, living systematic reviews with pairwise meta-analyses and network meta-analyses ...... 9 Figure 1.2-2: Global Coronavirus COVID-19 Clinical Trial Tracker - a real-time dashboard of clinical trials for COVID-19 ...... 10

Table 1.2-1: International Sources ...... 8 Table 2-1: Vaccines in the R&D pipeline (Phase 1 - Phase 3 clinical trials, not preclinical stages) ...... 14 Table 3-1: COVID-19 medicines that have received EMA advice ...... 31 Table 3-2: Most advanced therapeutics in the R&D pipeline ...... 32 Table 3.1-1: Summary of findings table on Remdesivir vs Standard care /Placebo (4 RCTs: Wang, Beigel, Spinner, SOLIDARITY-Remdesivir) ...... 37 Table 3.1-2: Summary of findings table on Remdesivir 5 days vs Remdesivir 10 days (2 RCTs: Goldman, Spinner) ...... 41 Table 3.3-1: Summary of findings table on favipiravir compared to umifenovir (1 RCT: Chen) ...... 45 Table 3.3-2: Summary of findings table on favipiravir compared to (1 RCT: Lou 2020) ...... 47 Table 3.3-3: Summary of findings table on favipiravir compared to lopinavir + ritonavir or darunavir/cobicistat + umifenovir + interferon-a (1 RCT: Lou 2020) ...... 48 Table 3.3-4: Summary of findings table on favipiravir compared to standard care (6 RCTs: Lou 2020, Ivashchenko 2020, Dabbous 2020, Balykova 2020, Ruzhentsova 2020, Udwadia 2020 ) ...... 49 Table 3.4-1: Summary of findings table on darunavir/cobicistat compared to standard care (1 RCT: Chen J) ...... 52 Table 3.9-1: Summary of findings table on tocilizumab compared standard care/placebo (6 RCTs: Rosas, Wang, Hermine, Salvarani, Stone, Salama) ...... 59 Table 3.11-1: Summary of findings table on Interferon β-1a compared to Standard Care for Moderate/Severe/Critical COVID-19 (3 RCTs: Davoudi-Monfared, Rahmani, SOLIDARITY-INF) ...... 64 Table 3.12-1: Summary of findings table on Convalescent plasma compared to Standard Care for Mild/Moderate/Severe/Critical COVID-19 (7 RCTs: Li, Gharbharan, Avendano-Sola, Agarwal, AlQahtani, Simonovich, Libster) ...... 69 Table 3.13-1: Summary of findings (SoF) table for published RCTs related to effectiveness and safety of bamlanivimab monotherapy (all doses) compared to placebo and bamlanivimab+etesevimab combination treatment – OUTPATIENT (1 RCT: Gottlieb 2021) ...... 77 Table 3.13-1 continued: Summary of findings (SoF) table for published RCTs related to effectiveness and safety of bamlanivimab + etesevimab combination compared to placebo – OUTPATIENT (1 RCT: Gottlieb 2021) ...... 79 Table 3.13-2: Summary of findings (SoF) table for published RCTs related to effectiveness and safety of bamlanivimab compared to standard treatment/placebo – HOSPITALISED (1 RCT: Lundgren et al. 2020) ...... 80

Table 3.14-1: Summary of findings table on triple combination of interferon beta-1b, lopinavir–ritonavir and ribavirin (1 RCT: Hung) ...... 85 Table 3.14-1 continued: : Summary of findings tables on Novaferon , Lopinavir/Ritonavir and Novaferon + Lopinavir/Ritonavir (1 RCT: Zheng 2020) ...... 87 Table 3.16-1. Summary of findings table, on umifenovir vs standard care (2 RCTs:Yueping, Yethindra) ...... 92 Table 3.17-1: Summary of findings table, on dexamethasone and other corticosteroids (7 RCTs: Horbey, Tomazini, Dequin, REMAP-CAP Investigators, Jeronimo, Corral, Edalatifard) ...... 98 Table 3.18-1: Summary of findings table, on anakinra (1 RCTs: CORIMUNO-19 Collaborative group) ...... 101 Table 3.19-1: Summary of findings table on colchicine compared to standard care (3 RCT: Deftereos, Lopes, Salehzadeh) ...... 105 Table 3.24-1: Summary of findings table on Vitamin D compared to standard care (3 RCT:Entrenas Castillo, Rastogi, Murai) ...... 110 Table 3.25-1: Summary of findings table, on baricitinib + remdesivir (1 RCT: Kalil 2020) ...... 110

On March 30th 2020, a request was raised by the Austrian Ministry of Health (BMASGK), the Health Funds of the Regions and the Federation of Social Insurances to set up a Horizon Scanning ystem (HSS) for medicines and vaccines. The establishment of a HSS/ Horizon Scanning System for Covid- 19 interventions has the intentions of a. informing health policy makers at an early stage which interventions (vaccinations and drugs) are currently undergoing clinical trials and b. monitoring them over the next few months in order to support evidence-based purchasing, if necessary.

To respond to this request, 1. As a first step an inventory, based on international sources, is built. 2. As a second step, selective searches by means of searches in study registries are carried out for information on clinical studies in humans and the state of research. 3. This information forms the basis for “vignettes” (short descriptions) for those products that are already in an "advanced" stage. 4. Subsequently, the products are monitored with regard to the status of the clinical studies up to approval and finally evaluated for their benefit and harm. All work steps are conducted in close international (European) cooperation.  Version 1 (V1, April 2020): inventory + vignettes for most advanced  Version 2+: monthly monitoring and updates Ongoing trials are reported in V1, April 2020 - V3, June 2020 of this Document and in the living documents - EUnetHTA (Covid-19 Rolling Collaborative Reviews: https://eunethta.eu/rcr01-rcrxx/). From V4 July, 2020 of this HSS/ Horizon Scanning Document, only completed, terminated, withdrawn and suspended interventional clinical trials from ClinicalTrials.gov and EUdraCT registers are re