Covid-19 roundup: Count­ing 1,087 tri­als for coro­n­avirus, R&D ex­perts say much of it is a com­plete waste; WHO sci­en­tist por­tends it will be 'years' be­fore Covid-19 threat will be con­tained

There are good ex­am­ples of R&D pro­grams for Covid-19 drugs and vac­cines, such as CEPI’s plan to ad­vance a slate of new pro­grams. But if you pull back and look at a land­scape of more than 1,000 clin­i­cal tri­als now un­der­way try­ing to make a mark, the field is a mess.

That, in blunt trans­la­tion, is the point of a new op-ed piece in the BMJ penned by Paul Glasziou, di­rec­tor of the In­sti­tute for Ev­i­dence Based Health­care, and col­leagues.

Ti­tling their piece “Waste in covid-19 re­search,” the team notes:

Be­fore the pan­dem­ic, it was es­ti­mat­ed that up to 85% of re­search was wast­ed be­cause of poor ques­tions, poor study de­sign, in­ef­fi­cien­cy of reg­u­la­tion and con­duct, and non or poor re­port­ing of re­sults. Many of these prob­lems are am­pli­fied in covid-19 re­search, with time pres­sures and in­ad­e­quate re­search in­fra­struc­ture con­tribut­ing.

The au­thors count­ed 1,087 clin­i­cal tri­als for Covid-19 in­ter­ven­tions on clin­i­cal­tri­, “and though some will pro­vide use­ful in­for­ma­tion, many are too small and poor­ly de­signed to be help­ful, mere­ly adding to the covid-19 noise. Of the 145 reg­is­tered tri­als of hy­drox­y­chloro­quine, for ex­am­ple, 32 have a planned sam­ple size of ≤100, 10 have no con­trol group, and 12 are com­par­a­tive but non-ran­domised. Out­come mea­sures vary wide­ly, and on­ly 50 seem to be mul­ti­cen­tre. Strik­ing­ly, on­ly one pro­vides a pro­to­col, and even lim­it­ed reg­istry de­tails re­veal un­jus­ti­fied out­come switch­ing.”

One of the oth­er prob­lems with the fran­tic rush in­to Covid-19, they add, is that non-drug in­ter­ven­tions, such as the use of masks in pre­vent­ing the spread of the virus, are be­ing ig­nored. — John Car­roll

WHO sci­en­tist por­tends it will be ‘years’ be­fore Covid-19 threat will be con­tained

Paint­ing a grim pic­ture at the Fi­nan­cial Times’ Glob­al Board­room dig­i­tal con­fer­ence, the World Health Or­ga­ni­za­tion’s chief sci­en­tist pre­dict­ed it will take some four to five years be­fore Covid-19 is con­trolled.

Apart from ther­a­peu­tics, there is a fever­ish ef­fort to de­vel­op a vac­cine glob­al­ly, with some sci­en­tists hop­ing to have an ear­ly taste of da­ta by the end of this year or ear­ly 2020. Pret­ty much all re­searchers agree that a safe and ef­fec­tive vac­cine is the on­ly way out of the cri­sis, but pro­duc­tion and eq­ui­table dis­tri­b­u­tion hur­dles re­main.

On Wednes­day, the WHO’s Soumya Swami­nathan in­di­cat­ed a myr­i­ad of fac­tors would de­ter­mine how long the threat of the coro­n­avirus will re­main in play, in­clud­ing whether it mu­tates, the con­tain­ment mea­sures im­posed and whether a vac­cine is de­vel­oped.

Pe­ter Pi­ot, pro­fes­sor of glob­al health at the Lon­don School of Hy­giene and Trop­i­cal Med­i­cine who was al­so speak­ing on the FT pan­el and is him­self re­cov­er­ing from the vi­ral in­fec­tion, said coun­tries should be think­ing about the sit­u­a­tion in terms of years, not months, and find ways to change the par­a­digm from lock­downs to more “gran­u­lar, tar­get­ed types of in­ter­ven­tions,” ac­cord­ing to the FT re­port.

He al­so stressed the im­por­tance of test­ing, in line with the WHO’s rec­om­men­da­tions. There is “no op­tion but to in­vest more in test­ing,” Pi­ot said. — Na­tal­ie Grover

Swiss drug­mak­er No­var­tis thinks a re­al­is­tic vac­cine time­line is “one and a half to two years”

Vac­cines are hard to make. On av­er­age, in the pre-pan­dem­ic era, a decade was a rea­son­able time­frame to de­vel­op a vac­cine, al­though some virus­es such as HIV have proved elu­sive so far to the sci­en­tif­ic tool­box. The record for the fastest-ever vac­cine is for Ebo­la, which rav­aged West­ern Africa be­tween 2014 and 2016 — and that time­line is five years.

But the glob­al im­pact of Covid-19 has trig­gered a gar­gan­tu­an ef­fort from sci­en­tists the world over, with some re­searchers promis­ing their first batch of sol­id da­ta by the end of this year — for ex­am­ple, the group at Ox­ford hopes to have vi­able da­ta by the fall.

Vas Narasimhan, chief of No­var­tis — a com­pa­ny that is not de­vel­op­ing a vac­cine — said that a vac­cine will like­ly on­ly be avail­able in “one and a half to two years” in line with a cau­tious­ly op­ti­mistic view of the phar­ma­ceu­ti­cal in­dus­try, Bloomberg re­port­ed, cit­ing an opin­ion piece pub­lished by the CEO in a Swiss pub­li­ca­tion.

While health reg­u­la­to­ry bod­ies in Eu­rope and the Unit­ed States have gen­er­al­ly agreed to weak­en the ev­i­den­tiary stan­dards for ear­ly vac­cine stud­ies giv­en the ex­panse of the coro­n­avirus cri­sis, sci­en­tists and ex­perts have preached cau­tion against these am­bi­tious time­lines.

Bill Gates, who was elect­ed to pour sub­stan­tial re­sources as part of his foun­da­tion to fight Covid-19, has said it could take be­tween 9 months to two years to de­liv­er a vac­cine. The vac­cine part­ner­ship be­tween Ox­ford, As­traZeneca and Vac­citech — which aims to make 100 mil­lion dos­es by the end of 2020 — in­cludes pro­vi­sions to dis­trib­ute the vac­cine to low and medi­um-in­come coun­tries, al­though the de­tails are sparse. Pres­i­dent Don­ald Trump’s re­cent­ly-an­nounced “Op­er­a­tion Warp Speed,” seeks to pro­duce 300 mil­lion im­mu­niza­tions by the end of this year. — Na­tal­ie Grover

France’s Abi­vax kicks off big Covid-19 tri­al with drug that is en­gi­neered to have a three-pronged at­tack on Covid-19: an­tivi­ral, an­ti-in­flam­ma­to­ry and tis­sue re­pair

With the French drugs and ethics agen­cies sign­ing off on a 1,034-pa­tient place­bo-con­trolled phase IIb/III tri­al, called miR-AGE, of the com­pa­ny’s ex­per­i­men­tal drug, ABX464, Abi­vax is hop­ing the drug will help pre­vent se­vere in­flam­ma­tion that leads to acute res­pi­ra­to­ry dis­tress syn­drome in el­der­ly or high-risk pa­tients suf­fer­ing from Covid-19.

The Parisian biotech’s oral ther­a­py, which is al­so be­ing eval­u­at­ed as a treat­ment for ul­cer­a­tive col­i­tis, has been shown to up­reg­u­late miR-124, a “phys­i­o­log­i­cal brake” of in­flam­ma­tion, as well as tamp down cy­tokines in­volved in the Covid-19 cy­tokine storm. Sep­a­rate­ly, in vi­vo da­ta sug­gest ABX464 in­hibits repli­ca­tion of SARS-CoV-2, the virus be­hind Covid-19, the com­pa­ny said.

“Un­for­tu­nate­ly, no pro­phy­lac­tic or ther­a­peu­tic treat­ment has shown much ef­fi­ca­cy in any rig­or­ous tri­al to treat the se­vere form of COVID-19; help­ing clin­i­cians pre­vent res­pi­ra­to­ry dis­tress and death in COVID-19 pa­tients and lim­it longer-term pul­monary dam­age is of para­mount ne­ces­si­ty,” said Abi­vax chief Hart­mut Ehrlich in a state­ment. “The ro­bust, rig­or­ous de­sign of the miR-AGE ABX464 tri­al en­sures we will draw valid sci­en­tif­ic and med­ical con­clu­sions …We al­ready have ABX464 cap­sules in stock to treat app. 50,000 pa­tients and could scale-up ABX464 man­u­fac­tur­ing for over one mil­lion pa­tients with­in months.”

Gilead’s an­tivi­ral remde­sivir is the on­ly drug that has been grant­ed emer­gency use au­tho­riza­tion in the Unit­ed States (it is al­so un­der re­view at the EMA) on the ba­sis of place­bo-con­trolled clin­i­cal tri­al da­ta. How­ev­er, on­ly the top-line num­bers have been re­leased; the de­tailed da­ta are still to come. Mean­while, dis­tri­b­u­tion and ac­cess are fraught, with its mak­er do­nat­ing its ini­tial sup­ply of dos­es for rough­ly 140,000 pa­tients to the fed­er­al gov­ern­ment, be­cause there is no por­tal for hos­pi­tals to ap­ply for ac­cess to the med­i­cine or out­lined cri­te­ria for how the drug will be dis­trib­uted and to whom, caus­ing con­ster­na­tion and de­spair for doc­tors and pa­tients alike. — Na­tal­ie Grover

For a look at all End­points News coro­n­avirus sto­ries, check out our spe­cial news chan­nel.

How Pa­tients with Epilep­sy Ben­e­fit from Re­al-World Da­ta

Amanda Shields, Principal Data Scientist, Scientific Data Steward

Keith Wenzel, Senior Business Operations Director

Andy Wilson, Scientific Lead

Real-world data (RWD) has the potential to transform the drug development industry’s efforts to predict and treat seizures for patients with epilepsy. Anticipating or controlling an impending seizure can significantly increase quality of life for patients with epilepsy. However, because RWD is secondary data originally collected for other purposes, the challenge is selecting, harmonizing, and analyzing the data from multiple sources in a way that helps support patients.

$DNA is once again on NYSE; FDA clears Soliris chal­lenger for the mar­ket; Flag­ship’s think­ing big again with eR­NA; and more

Welcome back to Endpoints Weekly, your review of the week’s top biopharma headlines. Want this in your inbox every Saturday morning? Current Endpoints readers can visit their reader profile to add Endpoints Weekly. New to Endpoints? Sign up here.

I still remember the uncertainty in the air last year when nobody was sure whether ASCO would cancel their in-person meeting. But it’s now back again for the second virtual conference, and Endpoints News is here for it. Check out our 2-day event reviewing the landscape of cancer R&D and send news our way.

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Re­gen­eron's Evkeeza shows promise in curb­ing high triglyc­erides, but will ge­net­ic dis­par­i­ties lim­it use?

When Regeneron scored an early approval for lipid lowering antibody Evkeeza back in February, the drugmaker cracked open a new pathway to lower abnormally high cholesterol levels. Now, Regeneron is chasing high triglycerides as well with some promising mid-stage data — but will genetic restrictions limit the drug’s use?

Regeneron’s Evkeeza (evinacumab) cut median triglyceride levels by more than 800 mg/dL (57%) in patients with a rare disorder causing abnormally high triglyceride levels compared with an overall increase of 50 mg/dL (1.8%) in participants on placebo, according to Phase II data presented Sunday at the virtual American College of Cardiology meeting.

Michael Dell (Richard Drew, AP Images)

'Dude, you're get­ting a Del­l' — as a new deep-pock­et biotech in­vestor

What happens when you marry longtime insiders in the global biotech VC game with the family fund of tech billionaire Michael Dell, a synthetic biology legend out of MIT and Harvard and the former director of the NCI?

Today, the answer is a newly financed, $200 million biotech SPAC now cruising the industry for a top player interested in finding a short cut to Nasdaq.

Orion Biotech Opportunities priced their blank check company today, raising $200 million with Dell’s multibillion-dollar MSD group’s commitment on investing another $20 million in a forward-purchase agreement.

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As­traZeneca's Farx­i­ga missed big on Covid-19 study, but it's tak­ing SGLT2 safe­ty da­ta as a sil­ver lin­ing

AstraZeneca hasn’t seen many setbacks in recent months for SGLT2 inhibitor Farxiga, which broke ground in heart failure and kidney disease regardless of diabetes diagnosis. But the British drugmaker had to admit defeat in taking Farxiga into Covid-19, but follow-up results add a bit of a silver lining to that trial’s safety data.

Of hospitalized Covid-19 patients dosed with AstraZeneca’s Farxiga, 11.2% experienced an organ failure or died after 30 days of therapy compared with 13.8% of those given placebo, according to follow-up data from the DARE-19 study revealed Sunday at the virtual American College of Cardiology meeting.

Vas Narasimhan (Photographer: Simon Dawson/Bloomberg via Getty Images)

No­var­tis whiffs on En­tresto study af­ter heart at­tacks — but that does­n't mean it's go­ing down qui­et­ly

If Novartis learned one thing from its interaction with the FDA over its latest heart failure approval for Entresto, it was that missing a primary endpoint may not be the nail in the coffin. Now, Entresto has missed again on a late-stage study in high-risk heart patients, and it’s already sowing the seeds for a path forward regardless.

Novartis’ Entresto couldn’t best standard-of-care ramipril in staving off a composite of deaths and heart failure events in patients with left ventricular systolic dysfunction and/or pulmonary congestion who have had a prior heart attack, according to topline data from the Phase III PARADISE-MI study revealed Saturday at the virtual American College of Cardiology meeting.

Pfiz­er, Bris­tol My­er­s' Eliquis flops in post-heart surgery pa­tients, spurring an 'un­ex­plained sig­nal' in cer­tain deaths

Pfizer and Bristol Myers Squibb’s non-warfarin blood thinner Eliquis has raced out to become the most prescribed drug of its class on the market — even overtaking warfarin’s long-time lead. But in tricky-to-treat patients after a valve replacement, an investigator-sponsored study couldn’t turn up benefit and raised a troubling safety signal.

Eliquis failed to show benefit over standard of care in preventing serious clinical outcomes after a transaortic valve replacement (TAVR) and was linked to an “unexplained signal” in a subset of populations with a higher rate of non-CV deaths who did not need blood thinners apart from the surgery, according to data presented Saturday at the virtual American College of Cardiology meeting.

BAR­DA slows its $9B en­gine for new Covid-19 ther­a­peu­tics

The Biomedical Advanced Research and Development Authority is cooling its jets in looking for new, potential Covid-19 treatments, at least in the near term.

An HHS spokesperson told Endpoints News via email, “to date, BARDA has obligated more than $9 billion for the development and/or purchase of 13 therapeutics, beginning in February 2020 with support to develop Regeneron’s monoclonal antibody therapeutic. Therapeutics are an important element of the COVID-19 response, and we are focused on the programs currently underway and/or in negotiation using the funds available to us.”

Gene ther­a­py from Bio­gen's $800M buy­out flops in mid-stage study, deal­ing blow to new am­bi­tions

The #2 candidate from Biogen’s $800 million ocular gene therapy buyout has failed in a mid-stage trial, dealing an early blow to the big biotech’s plans to revitalize its pipeline with new technologies.

Biogen announced that the candidate, an experimental treatment for a rare and progressive form of blindness called X-linked retinitis pigmentosa (XLRP), failed to sufficiently improve vision in patients’ treated eye — patients only received an injection in one eye — after a year, on a standard scale, compared to their untreated eye. The company said they saw “positive trends” on several secondary endpoints, including visual acuity, but declined to say whether the trial actually hit any of those endpoints.

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