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|
|Early phase 1||1,868||4|
|Source: EvaluatePharma; excludes observational and epidemiology studies, and patient registries.|