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 clin­i­cal­tri­als.gov, “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.

BiTE® Plat­form and the Evo­lu­tion To­ward Off-The-Shelf Im­muno-On­col­o­gy Ap­proach­es

Despite rapid advances in the field of immuno-oncology that have transformed the cancer treatment landscape, many cancer patients are still left behind.1,2 Not every person has access to innovative therapies designed specifically to treat his or her disease. Many currently available immuno-oncology-based approaches and chemotherapies have brought long-term benefits to some patients — but many patients still need other therapeutic options.3

Covid-19 roundup: Mod­er­na read­ies to en­ter PhI­II in Ju­ly, As­traZeneca not far be­hind; EU ready to ne­go­ti­ate vac­cine ac­cess with $2.7B fund

Moderna may soon add another first to the Covid-19 vaccine race.

In March, the mRNA biotech was the first company to put a Covid-19 vaccine into humans. Next month, they may become the first company to put their vaccine into the large, late-stage trials that are needed to prove whether the vaccine is effective.

In an interview with JAMA editor Howard Bauchner, NIAID chief Anthony Fauci said that a 30,000-person, Phase III trial for Moderna’s vaccine could start in July. The news comes a week after Moderna began a Phase II study that will enroll several hundred people.

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Is a pow­er­house Mer­ck team prepar­ing to leap past Roche — and leave Gilead and Bris­tol My­ers be­hind — in the race to TIG­IT dom­i­na­tion?

Roche caused quite a stir at ASCO with its first look at some positive — but not so impressive — data for their combination of Tecentriq with their anti-TIGIT drug tiragolumab. But some analysts believe that Merck is positioned to make a bid — soon — for the lead in the race to a second-wave combo immuno-oncology approach with its own ambitious early-stage program tied to a dominant Keytruda.

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FDA de­lays de­ci­sion on No­var­tis’ po­ten­tial block­buster MS drug, wip­ing away pri­or­i­ty re­view

So much for a speedy review.

In February, Novartis announced that an application for their much-touted multiple sclerosis drug ofatumumab had been accepted and, with the drug company cashing in on one of their priority review vouchers, the agency was due for a decision by June.

But with June less than 48 hours old, Novartis announced the agency has extended their review, pushing back the timeline for approval or rejection to September. The Swiss pharma filed the application in December, meaning their new schedule will be nearly in line with the standard 10-month window period had they not used the priority voucher.

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Leen Kawas, Athira CEO (Athira)

Can a small biotech suc­cess­ful­ly tack­le an Ever­est climb like Alzheimer’s? Athi­ra has $85M and some in­flu­en­tial back­ers ready to give it a shot

There haven’t been a lot of big venture rounds for biotech companies looking to run a Phase II study in Alzheimer’s.

The field has been a disaster over the past decade. Amyloid didn’t pan out as a target — going down in a litany of Phase III failures — and is now making its last stand at Biogen. Tau is a comer, but when you look around and all you see is destruction, the idea of backing a startup trying to find complex cocktails to swing the course of this devilishly complicated memory-wasting disease would daunt the pluckiest investors.

GSK presents case to ex­pand use of its lu­pus drug in pa­tients with kid­ney dis­ease, but the field is evolv­ing. How long will the mo­nop­oly last?

In 2011, GlaxoSmithKline’s Benlysta became the first biologic to win approval for lupus patients. Nine years on, the British drugmaker has unveiled detailed positive results from a study testing the drug in lupus patients with associated kidney disease — a post-marketing requirement from the initial FDA approval.

Lupus is a drug developer’s nightmare. In the last six decades, there has been just one FDA approval (Benlysta), with the field resembling a graveyard in recent years with a string of failures including UCB and Biogen’s late-stage flop, as well as defeats in Xencor and Sanofi’s programs. One of the main reasons the success has eluded researchers is because lupus, akin to cancer, is not just one disease — it really is a disease of many diseases, noted Al Roy, executive director of Lupus Clinical Investigators Network, an initiative of New York-based Lupus Research Alliance that claims it is the world’s leading private funder of lupus research, in an interview.

José Basel­ga finds promise in new class of RNA-mod­i­fy­ing can­cer tar­gets, lock­ing in 3 pre­clin­i­cal pro­grams with $55M

Having dived early into some of the RNA breakthroughs of the last decades — betting on Moderna’s mRNA tech and teaming up with Silence on the siRNA front — AstraZeneca is jumping into a new arena: going after proteins that modify RNA.

Their partner of choice is Accent Therapeutics, which is receiving $55 million in upfront payment to steer a selected preclinical program through to the end of Phase I. After AstraZeneca takes over, the Lexington, MA-based startup has the option to co-develop and co-commercialize in the US — and collect up to $1.1 billion in milestones in the long run. The deal also covers two other potential drug candidates.

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President Donald Trump (left) and Moncef Slaoui, head of Operation Warp Speed (Alex Brandon, AP Images)

UP­DAT­ED: White House names fi­nal­ists for Op­er­a­tion Warp Speed — with 5 ex­pect­ed names and one no­table omis­sion

A month after word first broke of the Trump Administration’s plan to rapidly accelerate the development and production of a Covid-19 vaccine, the White House has selected the five vaccine candidates they consider most likely to succeed, The New York Times reported.

Most of the names in the plan, known as Operation Warp Speed, will come as little surprise to those who have watched the last four months of vaccine developments: Moderna, which was the first vaccine to reach humans and is now the furthest along of any US effort; J&J, which has not gone into trials but received around $500 million in funding from BARDA earlier this year; the joint AstraZeneca-Oxford venture which was granted $1.2 billion from BARDA two weeks ago; Pfizer, which has been working with the mRNA biotech BioNTech; and Merck, which just entered the race and expects to put their two vaccine candidates into humans later this year.

UP­DAT­ED: Es­ti­mat­ing a US price tag of $5K per course, remde­sivir is set to make bil­lions for Gilead, says key an­a­lyst

Data on remdesivir — the first drug shown to benefit Covid-19 patients in a randomized, controlled trial setting — may be murky, but its maker Gilead could reap billions from the sales of the failed Ebola therapy, according to an estimate by a prominent Wall Street analyst. However, the forecast, which is based on a $5,000-per-course US price tag, triggered the ire of one top drug price expert.