Table 1.
Dose optimisation of repurposed and new molecular entities for SARS-CoV-2 and COVID-19 as of summer 2021
| Drug (manufacturer) |
Dedicated COVID-19 dose-finding study | Post-RCT dose optimisation or supply Expansion clinical trial | Defined dose–response relationship or MDSE |
| Repurposed molecular entities | |||
| Anto-SARS-CoV-2 drugs | |||
| Remdesivir (Gilead) |
None (Ebola dose)47 |
5 vs 10 days duration48 | No |
| Immunomodulators | |||
| Anti-IL6 | |||
| Sarilumab (Sanofi) |
None, two dosing arms in randomised phase 3 trial49 | N/A | No |
| Tocilizumab (Genentech/Roche) |
None (CAR-T CRS dose)50 |
Adaptive dose-ranging phase 2, 4 dose levels23 Confirmatory RCT ongoing51 |
No |
| Anti-JAK/STAT | |||
| Baricitinib (+remdesivir) (Eli Lilly) |
None (EMA dose)52 |
Phase 1/2, including 4 mg and 2 mg53 | No |
| Corticosteroids | |||
| Dexamethasone (various) |
None (Sepsis/ARDS dose)54 |
10 mg daily (experimental) vs 6 mg daily (authorised dose) ongoing55 | No |
| Hydrocortisone (various) |
None (Sepsis/ARDS dose)56 |
None | No |
| New molecular entities | |||
| Vaccine | |||
| mRNA-1273 (Elasomeran (INN)) (Moderna) |
Non-human primate (two dose levels)57 | Surrogate endpoint-based, 50 µg vs 100 µg22 | No |
| BNT162b2 (Tozinameran (INN)) (Pfizer/BioNTech) |
Randomised, phase 1/2, 5 dose levels58 59 | Simulation-based study of lower doses17 Heterologous combo (BNT162b2, ChAdOx1 nCov-19) |
No |
| Ad26.COV2.S (Janssen) |
Randomised phase 1/2, 2 dose levels60 | No | No |
| ChAdOx1 nCov-19 (AstraZeneca-Oxford) |
Randomised phase 1/2, 2 dose cohorts (single vs two doses, all same dose)61 | Heterologous combination (BNT162b2 and ChAdOx1 nCov-19) | No |
| Anti-SARS-CoV-2 Drugs | |||
| Bamlanivimab Etesevimab (Eli Lilly) |
Randomised phase 1/2/3, 3 dose levels (bamlanivimab)62 Randomised phase 1/2/3, 2 dose levels (etesevimab)62 |
No | No |
| Casirivimab Imdevimab (Regeneron) |
Randomised phase 1/2/3, 2 dose levels (combination)63 | No | No |
| Sotrovimab (GlaxoSmithKline) |
Industry-sponsored randomised phase 1/2/3 (no dose range)64 | No | No |
Drugs that have received regulatory approval or authorisation, as well as U.S. guideline-recommended drugs, for the prevention or treatment of COVID-19 are summarised in the table. From left to right, columns demonstrate minimal pre-RCT dose-finding in COVID-19, a limited number of welfare-maximising dose optimisation trials, and the absence of any MDSE identification in COVID-19 therapeutics.
ARDS, acute respiratory distress syndrome; CAR-T CRS, chimeric antigen T-cell receptor-related cytokine release syndrome; EMA, European Medicines Agency; IL-6, interleukin 6; JAK, Janus kinase; MDSE, minimum dose with satisfactory efficacy; RCT, randomised controlled trial; STAT, signal transducer and activator of transcription proteins.