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.

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.

https://www.evaluate.com/vantage/articles/analysis/what-look-upcoming-covid-19-trial-readouts