Covid-19 roundup: Mod­er­na en­lists Catal­ent as man­u­fac­tur­ing part­ner, se­cur­ing fill-fin­ish ca­pac­i­ty for the first 100M dos­es

With Phase III tri­als now out­lined, lock­ing in a net­work of pro­duc­tion part­ners ap­pears to be top of mind for the lead­ing Covid-19 vac­cine de­vel­op­ers. In the lat­est move, Mod­er­na has named Catal­ent a col­lab­o­ra­tor for the large-scale, com­mer­cial fill-fin­ish man­u­fac­tur­ing of its mR­NA-based can­di­date.

Catal­ent — which has signed deals with As­traZeneca, J&J and Arc­turus — will pro­vide vial fill­ing and pack­ag­ing ca­pac­i­ty for an ini­tial 100 mil­lion dos­es in­tend­ed to sup­ply the US mar­ket start­ing the third quar­ter of this year. Ad­di­tion­al staffing at its Bloom­ing­ton, In­di­ana site will be de­ployed to guar­an­tee round-the-clock, 24/7 op­er­a­tions.

Mod­er­na might yet sign up for more, but the arrange­ments for those hun­dreds of mil­lions of dos­es are still un­der ne­go­ti­a­tions.

The CRO is al­so help­ing with the Phase III pro­gram, of­fer­ing clin­i­cal sup­ply ser­vices from the fa­cil­i­ties in Philadel­phia such as pack­ag­ing and la­bel­ing, as well as stor­age and dis­tri­b­u­tion.

Juan An­dres

“We ap­pre­ci­ate this col­lab­o­ra­tion with Catal­ent and the flex­i­bil­i­ty of their team to de­liv­er crit­i­cal fill-fin­ish ca­pac­i­ty for mR­NA-1273 at un­prece­dent­ed speed,” Juan An­dres, Mod­er­na’s chief tech­ni­cal op­er­a­tions and qual­i­ty of­fi­cer, said in a state­ment high­light­ing the race with time.

The Cam­bridge, MA-based biotech op­er­ates its own man­u­fac­tur­ing fa­cil­i­ty in Nor­wood, MA, a key ad­van­tage it’s con­stant­ly boast­ed. At the same time, it’s re­cent­ly be­gun tech trans­fer to Lon­za as part of a bil­lion-dose pact struc­tured for the long haul.

Knee deep in the ef­fort to de­liv­er a vac­cine can­di­date at warp speed, Catal­ent is al­so uti­liz­ing sites in Madi­son, WI and Anag­ni, Italy to scale up man­u­fac­tur­ing for oth­er part­ners.

NIH may have own­er­ship of Mod­er­na’s vac­cine. So what?

As an ap­proval for Mod­er­na’s Covid-19 vac­cine seems in­creas­ing­ly like­ly and im­mi­nent, con­sumer ad­vo­cates are shin­ing a spot­light on the NIH’s role in in­vent­ing it, lay­ing ground for fu­ture ar­gu­ments for the gov­ern­ment to make it a free or low-cost pub­lic good.

Fran­cis Collins NIH

Cit­ing a ma­te­r­i­al trans­fer agree­ment be­tween the NIH and Mod­er­na on mR­NA coro­n­avirus vac­cine can­di­dates and patent ap­pli­ca­tion dis­clo­sures un­cov­ered by Pub­lic Cit­i­zen, Ax­ios re­port­ed that the fed­er­al agency may co-own mR­NA-1273. And if they do, Pub­lic Cit­i­zen ar­gued, they could more broad­ly li­cense the vac­cine (as­sum­ing clin­i­cal suc­cess) to man­u­fac­tur­ers whether Mod­er­na agrees with it or not.

Not that the NIH might be par­tic­u­lar­ly keen to ex­er­cise these pow­ers. Fran­cis Collins, the di­rec­tor, was quot­ed in an Eco­nom­ic Club in­ter­view in May say­ing his agency does have “some par­tic­u­lar stake in the in­tel­lec­tu­al prop­er­ty.” But he added: “Talk­ing to the com­pa­nies, I don’t hear any of them say they think this [vac­cine] is a mon­ey-mak­er. I think they want to re­coup their costs and maybe make a tiny per­cent­age of in­crease of prof­it over that, like sin­gle dig­its per­cent­age-wise, but that’s it. No­body sees this as a way to make bil­lions of dol­lars.”

ICER up­dates pric­ing mod­els, adding new con­sid­er­a­tions on Gilead’s pric­ing of remde­sivir 

Al­most two months af­ter ICER first of­fered two dif­fer­ent pric­ing mod­els serv­ing as book­ends to the dis­cus­sion on how much Gilead should charge for remde­sivir, the pric­ing watch­dog has up­dat­ed its cal­cu­la­tions. Per­haps most im­por­tant­ly, the group in­cor­po­rat­ed a new sce­nario that can sig­nif­i­cant­ly re­duce the price bench­mark even un­der the more gen­er­ous mod­el.

Sev­er­al things have hap­pened since ICER pub­lished its ini­tial guide­lines: Gener­ic pro­duc­ers in Bangladesh and In­dia have an­nounced their prices; Gilead re­vealed more about their R&D in­vest­ment and plan; and British re­searchers came up with “strik­ing” — though pre­lim­i­nary — da­ta sug­gest­ing that a com­mon steroid, dex­am­etha­sone, can help se­vere Covid-19 pa­tients. The NIH al­so post­ed the full dataset for the ran­dom­ized, con­trolled remde­sivir tri­al. All of these de­vel­op­ments fed in­to the new mod­els.

Where­as Gilead could’ve charged $10 for a 10-day course un­der the pre­vi­ous cost-re­cov­ery mod­el, ICER now says they would need to price high­er to sim­ply re­coup the mar­gin­al cost of mak­ing the drug.

ICER’s up­dat­ed cost-re­cov­ery bench­mark price range for a full course of remde­sivir is $10 to $600 if on­ly con­sid­er­ing the mar­gin­al cost of pro­duc­ing the treat­ment, and $1,010 to $1,600 if al­so con­sid­er­ing the man­u­fac­tur­er’s fore­cast­ed 2020 clin­i­cal de­vel­op­ment ex­pens­es re­lat­ed to the treat­ment.

The $1,000 for each course of treat­ment sold was based on the as­sump­tion that Gilead would sell around 1 mil­lion cours­es to cov­er $1 bil­lion in R&D spend­ing.

Steven Pear­son ICER

De­ter­min­ing the cost-ef­fec­tive­ness thresh­old, on the oth­er hand, was more com­plex. Un­der old as­sump­tions ad­just­ed to new de­tails from the NIH’s ACTT1 num­bers, Gilead could rea­son­ably charge $4,580 to $5,080 per treat­ment course. If you fac­tor in dex­am­etha­sone, the range falls im­me­di­ate­ly to $2,520 to $2,800. And if you get re­al­ly strict and as­sume no mor­tal­i­ty ben­e­fit — some­thing remde­sivir didn’t demon­strate at sta­tis­ti­cal sig­nif­i­cance — it drops to $310.

All of these, as usu­al, are meant to spur dis­cus­sions, ICER pres­i­dent Steven Pear­son said.

“Re­ac­tion to our ini­tial ICER-COVID analy­ses con­firms pol­i­cy­mak­ers are ea­ger to weigh and de­bate mul­ti­ple ap­proach­es to pric­ing in a pan­dem­ic,” he said in a state­ment. “As with all drug pric­ing de­ci­sions, pol­i­cy mak­ers should weigh po­ten­tial oth­er ben­e­fits of treat­ment and broad­er con­tex­tu­al con­sid­er­a­tions as im­por­tant in fram­ing the re­sults of cost-re­cov­ery and cost-ef­fec­tive­ness analy­ses. Fu­ture up­dates to our re­port will con­tin­ue to as­sess the evolv­ing clin­i­cal land­scape, in­clud­ing emerg­ing peer-re­viewed da­ta on remde­sivir, dex­am­etha­sone, and oth­er emerg­ing ther­a­pies.”

Vaxart aims at 1 bil­lion dos­es of oral vac­cine with lat­est MOU

And it’s not on­ly the big play­ers. Vaxart, the South San Fran­cis­co-based de­vel­op­er of oral vac­cines, said it’s reached a ten­ta­tive deal with a part­ner that can en­able pro­duc­tion of a bil­lion or more dos­es of its Covid-19 vac­cine can­di­date.

At­twill Med­ical So­lu­tions would be­gin prepar­ing the re­sources and equip­ment need­ed for freeze-dry­ing, tablet­ing and en­teric coat­ing un­der a for­mal agree­ment.

It would join a group of CD­MO part­ners, in­clud­ing Kin­dred­Bio and Emer­gent BioSo­lu­tions, that have com­mit­ted to mak­ing the re­com­bi­nant pro­tein vac­cine.

“We be­lieve our oral vac­cines, gen­er­at­ed on our proven plat­form, have the po­ten­tial to of­fer su­pe­ri­or pro­tec­tion against air­borne virus­es such as SARS-CoV-2 by trig­ger­ing both mu­cos­al and sys­temic im­mu­ni­ty while be­ing ad­min­is­tered by a room tem­per­a­ture-sta­ble tablet, an enor­mous lo­gis­ti­cal ad­van­tage in large vac­ci­na­tion cam­paigns,” An­drei Floroiu, who’s re­cent­ly tapped as CEO to re­place Wouter La­tour, said in a state­ment.

A Phase I study of the Covid-19 can­di­date can be­gin as ear­ly as this sum­mer. While it’s had years of ex­pe­ri­ence with coro­n­avirus, norovirus, flu, res­pi­ra­to­ry syn­cy­tial virus and the hu­man pa­pil­lo­mavirus, though, Vaxart has yet to get a prod­uct across the fin­ish line in its decades of ex­is­tence.

EMA of­fi­cial­ly rec­om­mends remde­sivir for con­di­tion­al ap­proval

As the US con­tin­ues to de­bate the price for remde­sivir — which cur­rent­ly claims the on­ly emer­gency use au­tho­riza­tion for a Covid-19 treat­ment — the EU has fol­lowed suit to rec­om­mend it for con­di­tion­al au­tho­riza­tion in the EU.

The an­tivi­ral de­vel­oped by Gilead is the first Covid-19 drug to re­ceive this rec­om­men­da­tion, ac­cord­ing to a state­ment. Japan and Sin­ga­pore have both green­light­ed it.

Reg­u­la­tors from the EMA said their de­ci­sion was main­ly based on da­ta from the NI­AID ACTT-1 study and sup­port­ed by oth­er stud­ies. Hav­ing be­gun as­sess­ing da­ta on April 30 even be­fore an ap­pli­ca­tion was filed, they not­ed the re­view hap­pened in “an ex­cep­tion­al­ly short time­frame.”

The ver­dict:

Tak­ing in­to con­sid­er­a­tion the avail­able da­ta, the Agency con­sid­ered that the bal­ance of ben­e­fits and risks had been shown to be pos­i­tive in pa­tients with pneu­mo­nia re­quir­ing sup­ple­men­tal oxy­gen; i.e., the pa­tients with se­vere dis­ease. Remde­sivir is giv­en by in­fu­sion (drip) in­to a vein and its use is lim­it­ed to health­care fa­cil­i­ties in which pa­tients can be mon­i­tored close­ly; liv­er and kid­ney func­tion should be mon­i­tored be­fore and dur­ing treat­ment, as ap­pro­pri­ate. Treat­ment should start with a 200-mg in­fu­sion on the first day, fol­lowed by one 100-mg in­fu­sion a day for at least 4 days and no more than 9 days.

It is now up to the Eu­ro­pean Com­mis­sion to grant a for­mal de­ci­sion, which is ex­pect­ed in the com­ing week.

Gilead has yet to an­nounce prices for any­where in the world, al­though In­di­an gener­ic mak­ers have said they will sell their ver­sions be­tween rough­ly $66 and $80.

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

Regeneron CEO Leonard Schleifer speaks at a meeting with President Donald Trump, members of the Coronavirus Task Force, and pharmaceutical executives in the Cabinet Room of the White House (AP Photo/Andrew Harnik)

OWS shifts spot­light to drugs to fight Covid-19, hand­ing Re­gen­eron $450M to be­gin large scale man­u­fac­tur­ing in the US

The US government is on a spending spree. And after committing billions to vaccines defense operations are now doling out more of the big bucks through Operation Warp Speed to back a rapid flip of a drug into the market to stop Covid-19 from ravaging patients — possibly inside of 2 months.

The beneficiary this morning is Regeneron, the big biotech engaged in a frenzied race to develop an antibody cocktail called REGN-COV2 that just started a late-stage program to prove its worth in fighting the virus. BARDA and the Department of Defense are awarding Regeneron a $450 million contract to cover bulk delivery of the cocktail starting as early as late summer, with money added for fill/finish and storage activities.

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UP­DAT­ED: Bio­gen shares spike as ex­ecs com­plete a de­layed pitch for their con­tro­ver­sial Alzheimer's drug — the next move be­longs to the FDA

Biogen is stepping out onto the high wire today, reporting that the team working on the controversial Alzheimer’s drug aducanumab has now completed their submission to the FDA. And they want the agency to bless it with a priority review that would cut the agency’s decision-making time to a mere 6 months.

The news drove a 10% spike in Biogen’s stock $BIIB ahead of the bell.

Part of that spike can be attributed to a relief rally. Biogen execs rattled backers and a host of analysts earlier in the year when they unexpectedly delayed their filing to the third quarter. That delay provoked all manner of speculation after CEO Michel Vounatsos and R&D chief Al Sandrock failed to persuade influential observers that the pandemic and other factors had slowed the timeline for filing. Actually making the pitch at least satisfies skeptics that the FDA was not likely pushing back as Biogen was pushing in. From the start, Biogen execs claimed that they were doing everything in cooperation with the FDA, saying that regulators had signaled their interest in reviewing the submission.

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Daniel O'Day, Gilead CEO (Kevin Dietsch/UPI/Bloomberg via Getty Images)

A new study points to $6.5B in pub­lic sup­port build­ing the sci­en­tif­ic foun­da­tion of Gilead­'s remde­sivir. Should that be re­flect­ed in the price?

By drug R&D standards, Gilead’s move to repurpose remdesivir for Covid-19 and grab an emergency use authorization was a remarkably easy, low-cost layup that required modest efficacy and a clean safety profile from just a small group of patients.

The drug OK also arrived after Gilead had paid much of the freight on getting it positioned to move fast.

In a study by Fred Ledley, director of the Center for Integration of Science and Industry at Bentley University in Waltham, MA, researchers concluded that the NIH had invested only $46.5 million in the research devoted to the drug ahead of the pandemic, a small sum compared to the more than $1 billion Gilead expected to spend getting it out this year, all on top of what it had already cost in R&D expenses.

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Covid-19 roundup: Mod­er­na sticks to Ju­ly for its Phase III as ru­mors swirl; Fol­low­ing US lead, EU buys up Covid-19 treat­ments

The Phase III might be delayed from its original early July goal, but Moderna says it will still kick off the pivotal study for what could ultimately be the first Covid-19 vaccine before the end of the month.

A day after Reuters reported that squabbling between the Cambridge biotech and government regulators had held up the trial by about two weeks, Moderna released a statement saying that they had completed enrollment of their 650-person Phase II trial and were on track to begin Phase III by the end of the month. The protocol for that study, which is meant to prove whether or not the vaccine can prevent people from becoming sick, has been finalized, they said.

Stephen Hahn, AP

Trump and Navar­ro press again for hy­drox­y­chloro­quine. Can the FDA stay in­de­pen­dent?

Tuesday morning, economist and Trump advisor Peter Navarro walked onto the White House driveway and promptly brought a political cloud back onto the FDA.

Speaking to a White House pool reporter, Navarro said that four Detroit doctors were, based on a single disputed study, filing for the FDA to again issue an emergency authorization for hydroxychloroquine, the anti-malarial pill that President Trump hyped for months as a Covid-19 treatment over the objections of his own scientists. Then, while avoiding directly calling for the FDA to OK the drug, blasted the agency. He said its decision to pull an earlier authorization “was based on bad science” and “had a tremendously negative effect” on doctors and patients.

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Donald and Melania Trump watch the smoke of fireworks from the South Lawn of the White House on July 4, 2020 (via Getty)

Which drug de­vel­op­ers of­fer Trump a quick, game-chang­ing ‘so­lu­tion’ as the pan­dem­ic roars back? Eli Lil­ly and Ab­Cellera look to break out of the pack

We are unleashing our nation’s scientific brilliance and will likely have a therapeutic and/or vaccine solution long before the end of the year.

— Donald Trump, July 4

Next week administration officials plan to promote a new study they say shows promising results on therapeutics, the officials said. They wouldn’t describe the study in any further detail because, they said, its disclosure would be “market-moving.”

— NBC News, July 3

Something’s cooking. And it’s not just July 4 leftovers involving stale buns and uneaten hot dogs.

Over the long weekend observers picked up signs that the focus in the Trump administration may swiftly shift from the bright spotlight on vaccines being promised this fall, around the time of the election, to include drugs that could possibly keep patients out of the hospital and take the political sting out of the soaring Covid-19 numbers causing embarrassment in states that swiftly reopened — as Trump cheered along.

So far, Gilead has been the chief beneficiary of the drive on drugs, swiftly offering enough early data to get remdesivir an emergency authorization and into the hands of the US government. But their drug, while helpful in cutting stays, is known for a limited, modest effect. And that won’t tamp down on the hurricane of criticism that’s been tearing at the White House, and buffeting the president’s most stalwart core defenders as the economy suffers.

We’ve had positive early-stage vaccine data, most recently from Pfizer and BioNTech, playing catchup on an mRNA race led by Moderna — where every little sign of potential trouble is magnified into a lethal threat, just as every advance excites a frenzy of support. But that race still has months to play out, with more Phase I data due ahead of the mid-stage numbers looming ahead. A vaccine may not be available in large enough quantities until well into 2021, which is still wildly ambitious.

So what about a drug solution?

Trump’s initial support for a panacea focused on hydroxychloroquine. But that fizzled in the face of data underscoring its ineffectiveness — killing trials that aren’t likely to be restarted because of a recent population-based study offering some support. And there are a number of existing drugs being repurposed to see how they help hospitalized patients.

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FDA bars the door — for now — against Mer­ck’s star can­cer drug af­ter Roche beat them to the punch

Merck has been handed a rare setback at the FDA.

After filing for the accelerated approval of a combination of their star PD-1 drug Keytruda with Eisai’s Lenvima as a first-line treatment for unresectable hepatocellular carcinoma, the FDA nixed the move, handing out a CRL because Roche beat them to the punch on the same indication by a matter of weeks.

According to Merck:

Ahead of the Prescription Drug User Fee Act action dates of Merck’s and Eisai’s applications, another combination therapy was approved based on a randomized, controlled trial that demonstrated overall survival. Consequently, the CRL stated that Merck’s and Eisai’s applications do not provide evidence that Keytruda in combination with Lenvima represents a meaningful advantage over available therapies for the treatment of unresectable or metastatic HCC with no prior systemic therapy for advanced disease. Since the applications for KEYNOTE-524/Study 116 no longer meet the criteria for accelerated approval, both companies plan to work with the FDA to take appropriate next steps, which include conducting a well-controlled clinical trial that demonstrates substantial evidence of effectiveness and the clinical benefit of the combination.

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Covid-19 roundup: Squab­bles with gov­ern­ment de­lay Mod­er­na’s PhI­II — re­ports; No­vavax se­cures largest Warp Speed deal yet: $1.6B

A much-anticipated Phase III trial for Moderna’s Covid-19 vaccine is being held up as the company delayed submitting trial protocols and sparred with government scientists on how to run the study and even what the benchmark for success should be, Reuters reported.

Moderna, the first US company to put their vaccine into human testing, was supposed to enter a 30,000-person study this month in partnership with the NIH to determine whether it can prevent infection. STAT reported last week that the trial was facing delays over the protocol, but that a July start was still possible. Neither the NIH nor Moderna ever disclosed a specific date the trial should start, but Reuters reported that the agency had hoped to begin on July 10.

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Zai Lab inks Chi­na deal with Turn­ing Point with $25M up­front; Xen­cor, Atre­ca team up on bis­pecifics

Zai Lab is paying out a $25 million upfront for the rights to sell Turning Point Therapeutics’ lead drug repotrectinib in Greater China. The San Diego-based biotech is also in line for up to $151 million in milestones, along with mid-to-high teen royalties. Zai plans to add sites to the Phase II trial of the drug, which is designed to treat ROS1-positive advanced NSCLC in patients who were not previously treated with a TKI.