What to look for in upcoming Covid-19 trial readouts

Industry-sponsored clinical studies against the new coronavirus have proliferated, as have their designs and efficacy measures.

Analysis

As attention in the battle to treat Covid-19 turns to the imminent readout of remdesivir studies in China investors will be trying to handicap the chances of Gilead’s own global trials, reading out a little later.

It is also worthwhile remembering other clinical studies that have recently got under way to treat and, in some cases, prevent the new coronavirus. An analysis of data on EvaluatePharma’s dedicated Covid-19 landing page reveals no fewer than 230 trials seeking to enrol nearly 200,000 subjects, but what should be especially interesting is the commercial studies and their endpoints.

This group comprises 20 trials of 17 projects, including of course Gilead’s two remdesivir studies, which could read out in May. A key consideration is whether studies have a blinded control, and in the case of remdesivir this is one of the main points differentiating Gilead from the Chinese trials.

The latter two tests, in 308 mild/moderate and 453 severe Covid-19 subjects, are quadruple-blinded and measure time to clinical recovery versus placebo. Gilead’s, meanwhile, are open-label: the moderate disease trial is versus standard of care while the severe is uncontrolled, and both measure disease improvement over 14 days.

Both sets of trials use a 200mg loading dose followed by 100mg for nine days, though Gilead’s also test five-day cohorts. On the one hand the China trials’ open-ended efficacy endpoint seems less strict than Gilead assuming an effect within 14 days, though of course the former’s blinded design is more stringent.

Another issue confounding comparisons is that the China groups recruited subjects within eight or 12 days of symptom onset, while Gilead specified up to four days from PCR confirmation of Covid-19. Evercore ISI says the former did not source remdesivir from Gilead, and Gilead has stated that it has no visibility on their data.

Commercial projects in clinical trials for Covid-19*
Project Company Study Enrolment Location Design Key efficacy measures
Remdesivir Gilead NCT04292730 600 Global Open-label 14-day hospital discharge vs SOC
Remdesivir Gilead NCT04292899 400 Global Uncontrolled 14-day fever normalisation
Plaquenil Sanofi Hydra 500 US & Mexico Quadruple-blinded All-cause mortality vs placebo
Plaquenil (prophylaxis) Sanofi Phydra 400 US & Mexico Quadruple-blinded 60-day Covid-19 infection vs placebo
Actemra Roche Covacta 330 ? Double-blinded 28-day clinical status vs placebo
Fludase Ansun Biopharma NCT03808922 250 Global Quadruple-blinded 28-return to room air vs placebo
CD24Fc Oncoimmune SAC-COVID 230 US Quadruple-blinded 14-day Covid-19 status vs placebo
ASC09 + Norvir Ascletis NCT04261907 160 China Open-label Time to recovery vs Kaletra
T89 Tasly NCT04285190 120 China Open-label Time to normal oxygen saturation vs placebo
Kevzara Sanofi/ Regeneron NCT04315298 400 US Quadruple-blinded % chg in CRP/time to improvement vs placebo
Kevzara Sanofi/ Regeneron NCT04327388 300 Europe Quadruple-blinded Fever resolution/15-day severity vs placebo
Kaletra Abbvie Solidarity 440 Canada Open-label 29-day Covid-19 infection vs SOC
PUL-042 (prophylaxis) Pulmotect NCT04313023 200 ? Quadruple-blinded 14-day Covid-19 prevention vs placebo
PUL-042 Pulmotect NCT04312997 100 US Quadruple-blinded 14-day Covid-19 severity vs placebo
IFX-1 Inflarx Panamo 130 Europe Open-label 5-day chg in PaO2/FiO2 vs SOC
Gamifant or Anakinra Swedish Orphan Biovitrum NCT04324021 54 Europe Open-label 15-day % off ventilation vs SOC
Piclidenoson Can-Fite NCT04333472 40 Israel Open-label Time to clinical recovery vs SOC
INOmax Mallinckrodt NONTM 20 Canada Uncontrolled FEV1 from baseline/QOL
mRNA-1273 (vaccine) Moderna NCT04283461 45 US Uncontrolled % seroconversion
Ad5-nCoV (vaccine) Cansino Biologics APICTH 108 China Uncontrolled Immunogenicity
*All projects therapeutic except where stated; excludes expanded-access programmes. Source: EvaluatePharma.

Among other projects, investors will also be keenly tracking the malaria/lupus drug Plaquenil, championed by President Donald Trump. Since the few scraps of data supporting this have largely been anecdotal, it is reassuring that Sanofi’s studies, ending late this year, are quadruple-blinded, and one measures the tough endpoint of all-cause mortality versus placebo.

Only two commercial vaccines are in trials at present, from Moderna and Cansino (The long path to an effective coronavirus vaccine, April 3, 2020). However, these will soon be joined by vaccines from Johnson & Johnson and the UK’s University of Oxford, the latter through a consortium that Oxford Biomedica joined today.

Ultimately, investors will want share prices to reflect progress; Gilead’s valuation has put on nearly $12bn year to date, while J&J’s gained $26bn when it revealed its lead Covid-19 vaccine candidate. This is despite J&J spelling out the not-for-profit basis of its work; Gilead too is unlikely to be able to charge much for remdesivir, while Plaquenil is off patent.

That said, the kudos for a company that brings an effective treatment to market, in terms of publicity and government recognition, will have its own value.

Covid-19 study totals
Stage Enrolment Trial count
Early phase 1 1,868 4
Phase 1 2,424 10
Phase 1/2 1,069 9
Phase 2 7,413 38
Phase 2/3 9,374 21
Phase 3 44,905 39
Phase 4 12,164 16
N/A 117,013 93
Total 196,230 230
Source: EvaluatePharma; excludes observational and epidemiology studies, and patient registries.

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