CEO Jonathan Javitt (NeuroRx)

Neu­roRx chief lines up Hail Mary for once-re­ject­ed Covid-19 drug

Neu­roRx’s Covid-19 treat­ment was al­ready shot down by the FDA once, and it failed the pri­ma­ry end­point in a Phase IIb/III read­out — but that won’t stop CEO Jonathan Javitt from lin­ing up a Hail Mary pass to reg­u­la­tors.

Javitt gave End­points News a pre­view of Phase IIb/III da­ta based on an ini­tial 28-day end­point on Mon­day af­ter­noon. At 28 days, crit­i­cal­ly ill Covid-19 pa­tients giv­en Neu­roRx and Re­lief Ther­a­peu­tics’ avip­tadil were 35% more like­ly to re­cov­er and be dis­charged from the hos­pi­tal com­pared to those on a place­bo, Javitt said. How­ev­er, the p-val­ue was 0.08 — falling well be­low the 0.05 p-val­ue need­ed to demon­strate sta­tis­ti­cal sig­nif­i­cance, mean­ing there’s a greater chance that the re­sults were ran­dom and not tied to the treat­ment.

“There’s 8 chances in 100 that the dif­fer­ence we ob­served could have been a ran­dom event ver­sus 5 chances in 100,” Javitt said at the time, ar­gu­ing that the “re­al­ly strong sig­nal” was me­di­an time to re­cov­ery and dis­charge.

At 28 days, the me­di­an time to get bet­ter and leave the hos­pi­tal was 10 days short­er for the avip­tadil pa­tients, with a p-val­ue of 0.006, Javitt said.

But ear­ly Tues­day morn­ing, Javitt reached out with changes to the sto­ry. While the Phase IIb/III was ini­tial­ly OK’d as a 28-day study, Neu­roRx added a 60-day end­point in De­cem­ber. The 28 days was “not ap­pro­pri­ate for crit­i­cal­ly ill pa­tients with Covid-19, who are fre­quent­ly main­tained in ICU with ad­vanced tech­nolo­gies well be­yond this time point,” the com­pa­ny said in a state­ment.

Javitt said the FDA re­leased new Covid-19 guid­ance on Mon­day chang­ing the re­quired time for mea­sur­ing the end­point of “alive and free of res­pi­ra­to­ry fail­ure” to 60 days, mak­ing the Phase IIb/III read­out an in­ter­im read­out.

“The 60-day end­point makes sense be­cause too many peo­ple are still in the ICU at day 28 to know the true out­come, al­though the ZYE­SA­MI pa­tients are 38% more like­ly to have re­cov­ered and gone home. That means the curves have a good chance of di­verg­ing fur­ther be­tween day 28 and day 60,” Javitt wrote in an email to End­points.

Rather than stat­ing that those in the avip­tadil arm were 35% more like­ly to re­cov­er and be dis­charged from the hos­pi­tal, Neu­roRx is now say­ing avip­tadil pa­tients had a “35% high­er like­li­hood of re­cov­ery from res­pi­ra­to­ry fail­ure with con­tin­ued sur­vival.”

“Should these trends con­tin­ue through day 60, they have the po­ten­tial to reach sta­tis­ti­cal sig­nif­i­cance,” the com­pa­ny said.

Up­dat­ed guid­ance post­ed to the FDA’s web­site on Mon­day says the pre-spec­i­fied end­point should be mea­sured af­ter at least 28 days for hos­pi­tal­ized non-crit­i­cal­ly ill pa­tients, and 60 days for crit­i­cal­ly ill pa­tients. The FDA re­spond­ed Wednes­day con­firm­ing that the pre­vi­ous guid­ance “re­ferred to ‘at least 28 days’ for se­vere and/or crit­i­cal­ly ill pa­tients.”

This is the sec­ond time Neu­roRx has changed their pri­ma­ry end­point. Ini­tial­ly, the pri­ma­ry end­points were blood oxy­gena­tion and mor­tal­i­ty, ac­cord­ing to a fil­ing on clin­i­cal­tri­als.gov.

In a sub­group of pa­tients in ter­tiary hos­pi­tals, those in the avip­tadil arm were 46% more like­ly to re­cov­er and re­turn home be­fore day 28, with a p-val­ue of 0.058, al­so above the bar. When asked why the big dif­fer­ence in the ter­tiary sub­group, Javitt spec­u­lat­ed it could have some­thing to do with hos­pi­tal ca­pac­i­ty.

“It may well be that the dif­fer­ence we saw be­tween the ter­tiary and the re­gion­al hos­pi­tals re­al­ly could have been a dif­fer­ence be­tween hos­pi­tals that were run­ning be­low ca­pac­i­ty and hos­pi­tals that were run­ning 200% of ca­pac­i­ty,” he said.

The on­ly side ef­fect ob­served was mild to mod­er­ate di­ar­rhea in 30% of pa­tients, Javitt said.

“In that con­text, to say ‘Well, you know, you shouldn’t give it be­cause there’s 3 more chances in 100 that that mea­sure could have been seen by chance, doesn’t seem very rea­son­able,” he ini­tial­ly said of the pre­view, be­fore mak­ing the changes. “EUA is based on a stan­dard of may be ef­fec­tive.”

Rea­son­able or not, the FDA has al­ready turned down avip­tadil once. Neu­roRx and Re­lief sub­mit­ted for an EUA in Sep­tem­ber based on a case-con­trol study with 21 pa­tients in the treat­ment arm and an­oth­er group who re­ceived max­i­mal stan­dard-of-care in the same ICU.

The FDA de­nied their bid last month, caus­ing Re­lief’s $RLFTF stock to plunge from about 40 cents on Dec. 29 to 31 cents on Dec. 30. On Mon­day, shares closed at 37 cents apiece.

Javitt says the first EUA sub­mis­sion was a “very nar­row” one, for pa­tients who would oth­er­wise qual­i­fy un­der an ex­pand­ed ac­cess pro­to­col but didn’t have a way to get the drug. He said the com­pa­ny was run­ning in­to sit­u­a­tions where hos­pi­tals didn’t have the in­fra­struc­ture to par­tic­i­pate in an EAP.

Af­ter be­ing de­nied an EUA, Neu­roRx end­ed up treat­ing some of those pa­tients un­der Right to Try laws, he said. To date, the drug has been ad­min­is­tered to about 520 pa­tients to­tal.

Neu­roRx came un­der fire ear­li­er in Sep­tem­ber af­ter Politi­co re­port­ed it tapped a Re­pub­li­can con­gress­man with close ties to its CEO and a his­to­ry of mask skep­ti­cism to their Da­ta and Safe­ty Mon­i­tor­ing Board. Javitt con­firmed that Rep. Andy Har­ris was hired to the DSMB, but de­nied that he is a mask skep­tic.

Har­ris said at a House Ap­pro­pri­a­tions sub­com­mit­tee hear­ing back in June that there was a “cult of masks,” and ques­tioned for­mer CDC di­rec­tor Robert Red­field about the agency’s guid­ance to wear cloth masks, as op­posed to sur­gi­cal masks or face shields.

Javitt said on Mon­day that the last pa­tient just fin­ished 60 days of treat­ment, and that he ex­pect­ed to file for an­oth­er EUA with­in a cou­ple weeks. As part of the Tues­day an­nounce­ment, he said they will file “should the above trends con­tin­ue through day 60.”

Feb 23: A pre­vi­ous ver­sion of this ar­ti­cle stat­ed up­on sec­ond ref­er­ence that those in the place­bo arm were 35% more like­ly to re­cov­er and be dis­charged in the hos­pi­tal. A cor­rec­tion has been made to re­flect that it was the avip­tadil arm.

Feb 26: An up­date has been made to re­flect that the FDA has con­firmed the changes to its guid­ance. 

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

The top 100 bio­phar­ma VCs, Bob Brad­way places $2B bet in can­cer, gene edit­ing pi­o­neer's new big idea, 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.

Before diving in, we had some news to share: Endpoints is launching a premium weekly report focusing on all things regulatory. Coverage will be led by our new senior editor, Zachary Brennan, who joins us from POLITICO. Arsalan Arif has more details in his Publisher’s Note.

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Robert Bradway (Photographer: Scott Eisen/Bloomberg via Getty Images)

UP­DAT­ED: Am­gen snaps up can­cer drug play­er Five Prime, adding PhI­II-ready FGFR2b drug in $2B M&A play

Amgen is making a long-awaited move on the M&A side, buying South San Francisco-based Five Prime $FPRX for close to $2 billion and adding a slate of new cancer drugs to the pipeline.

Amgen is paying $38 a share, putting the deal value at $1.9 billion. The stock closed at $21.26 last night, giving investors a 78% premium.

The jewel in the crown of this deal is bemarituzumab, which Amgen describes as a first-in-class, Phase III-ready anti-FGFR2b antibody. Amgen was drawn to the bargaining table by Five Prime’s mid-stage data on gastric cancer, satisfied by PFS and OS data helping to validate FGFR2b as a target. Amgen researchers will now expand on the R&D program in other epithelial cancers, including lung, breast, ovarian and other cancers.

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David Liu (Casey Atkins Photography courtesy Broad Institute)

David Liu has a new big idea: pro­teome edit­ing. It could one day shred tau, RAS and some of the worst dis­ease-caus­ing pro­teins

Before David Liu became famous for inventing new forms of gene editing, he was known around academia in part for a more obscure innovation: a Rube Goldberg-esque system that uses bacteria-infecting viruses to take one protein and turn it into another.

Since 2011, Liu’s lab has used the system, called PACE, to dream up fantastical new proteins: DNA base editors far more powerful than the original; more versatile forms of the gene editor Cas9; insecticides that kill insecticide-resistant bugs; enzymes that slide synthetic amino acids into living organisms. But they struggled throughout to master one of the most common and powerful proteins in the biological world: proteases, a set of Swiss army knife enzymes that cut, cleave or shred other proteins in everything from viruses to humans.

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The 2021 top 100 bio­phar­ma in­vestors: As the pan­dem­ic hit and IPOs boomed, VCs swung in­to ac­tion like nev­er be­fore

The global pandemic may have roiled economies, killed hundreds of thousands and throttled entire industries, but the only effect it had on biopharma venture investing was to help turbocharge the field to giddy new heights.

Below you’ll find the new top 100 venture investors in the industry, ranked by the number of deals they were publicly involved in, as tracked by DealForma chief Chris Dokomajilar. The numbers master then calculated the estimated amount of money they put into each deal — divvying up the cash by the number of players — to indicate how they managed their syndicates.

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Eli Lil­ly claims a TKO in its long-run­ning ti­tle fight with No­vo Nordisk for the block­buster di­a­betes mar­ket — but there’s a hitch

Eli Lilly isn’t just gunning for a better diabetes drug in tirzepatide. They want to cut ahead of Novo Nordisk’s blockbuster rival Ozempic (semaglutide) on the obesity front as well. But a newly-claimed win in a head-to-head Phase III showdown over reducing A1C while shedding pounds — complete with clear evidence of superiority over the approved rival — could prove a tough sell right now.

Let’s start with the latest data from Lilly.

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Hal Barron, Endpoints UKBIO19

GSK, Vir's hopes for a Covid-19 an­ti­body fall flat in NIH 'mas­ter pro­to­col' with no ben­e­fit in hos­pi­tal­ized pa­tients

GlaxoSmithKline and Vir Biotechnology were hopeful that one of their partnered antibodies would carve out a win after getting the invite to a major NIH study in hospitalized Covid-19 patients. But just like Eli Lilly, the pair’s drug couldn’t hit the mark, and now they’ll be left to take a hard look at the game plan.

The NIH has shut down enrollment for GSK and Vir’s antibody VIR-7831 in its late-stage ACTIV-3 trial after the drug showed negligible effect in achieving sustained recovery in hospitalized Covid-19 patients, the partners said Wednesday.

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Cedric Francois, Apellis CEO (Apellis)

Apel­lis joins the grow­ing num­ber of bio­phar­mas scrap­ping a failed Covid-19 pro­gram af­ter an ear­ly flop

The global pandemic set off a frenzy of R&D activity as biotechs around the world scrambled to see if they could come up with a new medication or vaccine to help fight back. But even as the mRNA standouts are highlighting the market El Dorado open to successful teams, the failures are starting to pile up.

Thursday afternoon it was Apellis’ $APLS turn to deep-six a new drug.

The biotech reports that their C3 therapy APL-9 had failed to move the needle on mortality when combined with standard of care, as compared to SOC alone.

Eli Lil­ly claims suc­cess in a new JAK in­di­ca­tion: hair loss

Over the last decade, drugmakers have proven JAK inhibitors can treat a smattering of immune-related diseases ranging from rheumatoid arthritis to Covid-19. Now Eli Lilly has pulled out a new one.

Lilly and its biotech partner Incyte announced Wednesday that their JAK inhibitor baricitinib effectively regrew patients’ hair in a Phase III trial for alopecia areata, an autoimmune condition that can cause sudden, severe and patchy hair loss. Lilly didn’t break down the results from the 546-patient trial, but the primary endpoint was improvement on a standard score for alopecia symptoms.

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Bruce Cozadd, Jazz CEO (Jazz Pharmaceuticals)

Jazz CEO Bruce Cozadd cam­paigned for 6 months to buy GW Phar­ma. A 90% pre­mi­um sealed the deal — along with $17.6M in ‘re­ten­tion’ in­cen­tives

Jazz CEO Bruce Cozadd didn’t beat around the bush.

In his first video meeting with GW Pharma chief Justin Gover last July 8, he offered to pay $172 a share to get the company, which had beaten the odds in getting its remarkable cannabinoid drug Epidiolex across the regulatory finish line for epilepsy. GW’s stock closed at $129 that day.

Cozadd had already done his homework on the financing to make sure he could swing it the way he wanted. He just needed to do some due diligence before making the non-binding bid firm.