Covid-19 roundup: As­traZeneca's Farx­i­ga fails PhI­II test; Sup­ply deal for Eli Lil­ly's so­lo bam­lanivimab of­fi­cial­ly can­celed

Around the same time As­traZeneca struck up a vac­cine part­ner­ship with Ox­ford last April, the phar­ma gi­ant al­so put to­geth­er a game plan to de­vel­op treat­ments — both new and re­pur­posed — for Covid-19. One of them has now end­ed in fail­ure.

The Phase III DARE-19 tri­al re­cruit­ed 1,250 pa­tients hos­pi­tal­ized with Covid-19 over the past year and gave half of them the di­a­betes drug Farx­i­ga on top of stan­dard of care ther­a­py.

When com­pared to those re­ceiv­ing place­bo, the drug didn’t hit sta­tis­ti­cal sig­nif­i­cance in ei­ther of the pri­ma­ry end­points: pre­vent­ing mea­sur­ing or­gan dys­func­tion and all cause mor­tal­i­ty, or im­prov­ing re­cov­ery (as mea­sured by a change in clin­i­cal sta­tus) at 30 days.

Fo­cus­ing on the bright side, Mene Pan­ga­los, EVP of bio­phar­ma­ceu­ti­cals R&D, not­ed: “Pri­or to the DARE-19 Phase III tri­al, there was lit­tle da­ta on the use of SGLT2 in­hibitors in hos­pi­talised pa­tients with COVID-19 and we have now helped to fill this knowl­edge gap.”

Mikhail Kosi­borod, the prin­ci­pal in­ves­ti­ga­tor of the tri­al and the VP of re­search at As­traZeneca part­ner Saint Luke’s Mid Amer­i­ca Heart In­sti­tute, echoed Pan­ga­los and called the find­ings “very in­ter­est­ing and valu­able.” De­tails are due to be re­leased at the Amer­i­can Col­lege of Car­di­ol­o­gy Sci­en­tif­ic Ses­sions in May.

While orig­i­nal­ly de­signed as a di­a­betes pill, Farx­i­ga has been shown across large stud­ies to have car­dio and re­nal pro­tec­tive ef­fects not just in that pop­u­la­tion but al­so for those with heart fail­ure with re­duced ejec­tion frac­tion and chron­ic kid­ney dis­ease (CKD). Co­in­ci­den­tal­ly, sci­en­tists had ob­served that Covid-19 pa­tients with “car­diac, re­nal and meta­bol­ic co­mor­bidi­ties” tend­ed to have poor out­comes — lead­ing As­traZeneca to test whether Farx­i­ga may help in this set­ting as well.

Like a slew of oth­er com­mer­cial drugs that bio­phar­ma com­pa­nies big and small tried to re­pur­pose, it didn’t. As­traZeneca it­self has al­ready con­clud­ed that Calquence, the block­buster BTK in­hibitor ap­proved for can­cer, made lit­tle dif­fer­ence in mor­tal­i­ty or sav­ing Covid-19 pa­tients from res­pi­ra­to­ry fail­ure.

While the phar­ma gi­ant didn’t spec­i­fy the next steps, it seems to im­ply that this will mark the end of the Farx­i­ga pro­gram in Covid-19.

US gov­ern­ment re­jigs an­ti­body sup­ply deal with Eli Lil­ly 

Days af­ter the US gov­ern­ment and Eli Lil­ly agreed to halt all dis­tri­b­u­tion of bam­lanivimab as a monother­a­py, the com­pa­ny said of­fi­cials have of­fi­cial­ly re­vised the an­ti­body sup­ply deal.

That means the pur­chase agree­ment for bam­lanivimab will be ter­mi­nat­ed, the com­pa­ny said in a state­ment, can­cel­ing the planned de­liv­ery of 350,836 dos­es the orig­i­nal agree­ment had called for.

Con­cerns of bam­lanivimab’s di­min­ished ef­fi­ca­cy against cer­tain coro­n­avirus vari­ants first led the US to stop di­rect or­der­ing of bam­lanivimab alone in three states, be­fore ex­tend­ing that ban to the whole coun­try. In­stead, hos­pi­tals could or­der ei­ther bam­lanivimab and ete­se­vimab to­geth­er or ete­se­vimab alone to pair with any re­main­ing dos­es of bam­lanivimab on hand.

The arrange­ment is now cod­i­fied in the mod­i­fied con­tract.

First de­vel­oped by Ab­Cellera, bam­lanivimab was the first mon­o­clon­al an­ti­body to gain an emer­gency use au­tho­riza­tion at the FDA. Lil­ly sub­se­quent­ly paired it with ete­se­vimab, which orig­i­nat­ed from Chi­na’s Jun­shi, gen­er­at­ing a sol­id slate of com­bo da­ta that led to an­oth­er EUA, al­so for mild to mod­er­ate Covid-19. To­geth­er, the two reg­i­mens were the sub­ject of a $1.2 bil­lion sup­ply deal.

As con­cerns grew that cer­tain vari­ants could evade an­ti­body treat­ments, the FDA has di­rect­ed both Lil­ly and Re­gen­eron to mon­i­tor ge­nom­ic data­base(s) for the emer­gence of glob­al vi­ral vari­ants and track how well their drugs can tack­le those vari­ants.

Chi­na is ready to join the mR­NA race

As Fo­s­un Phar­ma pre­pares to push BioN­Tech’s Covid-19 vac­cine to­ward an ap­proval in Chi­na, a se­nior in­dus­try fig­ure says home­grown mR­NA play­ers will al­so be ready to jump in the game soon.

“We ful­ly ex­pect that there is a high pos­si­bil­i­ty that a do­mes­tic mR­NA vac­cine will hit the mar­ket by this year,” Feng Duo­jia, pres­i­dent of the Chi­na As­so­ci­a­tion of Vac­cines, told the South Chi­na Morn­ing Post.

One can­di­date joint­ly de­vel­oped by the Acad­e­my of Mil­i­tary Sci­ence, Wal­vax Biotech­nol­o­gy and Suzhou Abo­gen Bio­sciences has been through Phase II tri­als with “sat­is­fac­to­ry” re­sults, he said, with Phase III tri­als un­der­way over­seas. An­oth­er from Shang­hai-based Stemir­na went in­to the clin­ic last month.

Fo­s­un, mean­while, is sort­ing through da­ta from Phase II tri­als con­duct­ed in Jiang­su province, SCMP re­port­ed. The plan is to com­bine those with Phase III re­sults from over­seas in its reg­u­la­to­ry fil­ing.

While Fo­s­un start­ed off as the de­vel­op­er and dis­trib­u­tor of BioN­Tech’s vac­cines — hav­ing start­ed de­liv­er­ing dos­es made in Ger­many to Hong Kong and Macau — the com­pa­ny has inked a deal to pro­duce lo­cal­ly.

“The prepa­ra­tions at the pro­duc­tion fa­cil­i­ty are ready,” Feng added. “Af­ter ef­fec­tive re­sults are ob­tained through these tri­als, an ap­pli­ca­tion will be sub­mit­ted to the rel­e­vant gov­ern­ment agency im­me­di­ate­ly, with the hope to start do­mes­tic pro­duc­tion of the for­eign vac­cine in Chi­na.”

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

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In­no­v­a­tive MedTech De­mands Spe­cial­ist Clin­i­cal Tri­al Reg­u­la­to­ry Af­fairs and De­sign

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Ted Love, Global Blood Therapeutics CEO

Up­dat­ed: Pfiz­er scoops up Glob­al Blood Ther­a­peu­tics and its sick­le cell ther­a­pies for $5.4B

Pfizer is dropping $5.4 billion to acquire Global Blood Therapeutics.

Just ahead of the weekend, word got out that Pfizer was close to clinching a $5 billion buyout — albeit with other potential buyers still at the table. The pharma giant, flush with cash from Covid-19 vaccine sales, apparently got out on top.

The deal immediately swells Pfizer’s previously tiny sickle cell disease portfolio from just a Phase I program to one with an approved drug, Oxbryta, plus a whole pipeline that, if all approved, the company believes could make for a $3 billion franchise at peak.

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BREAK­ING: Math­ai Mam­men makes an abrupt ex­it as head of the big R&D group at J&J

In an after-the-bell shocker, J&J announced Monday evening that Mathai Mammen has abruptly exited J&J as head of its top-10 R&D group.

Recruited from Merck 5 years ago, where the soft spoken Mammen was being groomed as the successor to Roger Perlmutter, he had been one of the top-paid R&D chiefs in biopharma. His group spent $12 billion last year on drug development, putting it in the top 5 in the industry.

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No­vavax shares shred­ded as Covid vac­cine sales fall more than 90% in Q2

Months after Novavax celebrated its first profitable quarter as a commercial company, the Gaithersburg, MD-based company is back in the red.

Sales for Novavax’s Covid-19 vaccine slipped to $55 million last quarter, down from $586 million in Q1, CEO Stanley Erck revealed on Monday after market close. The company’s stock $NVAX plummeted more than 32% in after-hours trading.

Upon kicking off the call with analysts and investors, Erck addressed the elephant in the room:

Uğur Şahin, BioNTech CEO (Kay Nietfeld/picture-alliance/dpa/AP Images)

De­spite falling Covid-19 sales, BioN­Tech main­tains '22 sales guid­ance

While Pfizer raked in almost $28 billion last quarter, its Covid-19 vaccine partner BioNTech reported a rise in total dose orders but a drop in sales.

The German biotech reported over $3.2 billion in revenue in Q2 on Monday, down from more than $6.7 billion in Q1, in part due to falling Covid sales. While management said last quarter that they anticipated a Covid sales drop — CEO Uğur Şahin said at the time that “the pandemic situation is still very much uncertain” — Q2 sales still missed consensus by 14%.

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FDA commissioner Rob Califf (Tom Williams/CQ Roll Call via AP Images)

With drug pric­ing al­most done, Con­gress looks to wrap up FDA user fee leg­is­la­tion

The Senate won’t return from its summer recess until Sept. 6, but when it does, it officially has 18 business days to finalize the reauthorization of the FDA user fee programs for the next 5 years, or else thousands of drug and biologics reviewers will be laid off and PDUFA dates will vanish in the interim.

FDA commissioner Rob Califf recently sent agency staff a memo explaining how, “Our latest estimates are that we have carryover for PDUFA [Prescription Drug User Fee Act], the user fee funding program that will run out of funding first, to cover only about 5 weeks into the next fiscal year.”

Pascal Soriot, AstraZeneca CEO (David Zorrakino/Europa Press via AP Images)

As­traZeneca and Dai­ichi Sankyo sprint to mar­ket af­ter FDA clears En­her­tu in just two weeks

Regulators didn’t keep AstraZeneca and Daiichi Sankyo waiting long at all for their latest Enhertu approval.

The partners pulled a win on Friday in HER2-low breast cancer patients who’ve already failed on chemotherapy, less than two weeks after its supplemental BLA was accepted. While this isn’t the FDA’s fastest approval — Bristol Myers Squibb won an OK for its blockbuster checkpoint inhibitor Opdivo in just five days back in March — it comes well ahead of Enhertu’s original Q4 PDUFA date.

Bernhardt Zeiher, outgoing Astellas CMO (Astellas)

Q&A: Astel­las' re­tir­ing head of de­vel­op­ment re­flects on gene ther­a­py deaths

For anyone who’s been following discussions about the safety alarms surrounding the adeno-associated viruses (AAV) commonly used to deliver gene therapy, Astellas should be a familiar name.

The Japanese pharma — which bought out Audentes Therapeutics near the end of 2019 and later built a gene therapy unit around the acquisition — rocked the field when it reported three patient deaths in a trial testing AT132, the lead program from Audentes designed to treat a rare muscle disease called X-linked myotubular myopathy (XLMTM).

When the company restarted the trial, it adjusted the dose and instituted a battery of other measures to try to prevent the same thing from happening again. But tragically, the first patient to receive the new regimen died just weeks after administration. The therapy remains under clinical hold, and just weeks ago, Astellas flagged another safety-related hold for a separate gene therapy candidate. In the process of investigating the deaths, the company has also taken flak about the way it disclosed information.

Big questions remain — questions that can have big implications about the future of AAV gene therapies.

Bernhardt Zeiher did not imagine any of it when he first joined Astellas as the therapeutic area leader in inflammation, immunology and infectious diseases. But his ascent to chief medical officer and head of development coincided almost exactly with Astellas’ big move into gene therapy, putting him often in the driver’s seat to grapple with the setbacks.

As Zeiher prepares to retire next month after a 12-year tenure — leaving the unfinished tasks to his successor, a seasoned cancer drug developer — he chatted with Endpoints News, in part, to discuss the effort to understand what happened, lessons learned and the criticism along the way.

The transcript has been lightly edited for length and clarity.

Endpoints: I want to also ask you a bit about the gene therapy efforts you’ve been working on. Astellas has really been at the forefront of discovering the safety concerns associated with AAV gene therapy. What’s that been like for you?

Zeiher: Well, I have to admit, it’s been a bit of a roller coaster. We acquired Audentes. Huge amount of enthusiasm. What we saw with AT132 — that was the lead program in XLMTM — was just remarkable efficacy. I mean, kids who went from being on ventilators, not able to eat for themselves, sit up, do things like that, to off ventilators, walking, you know, really — one investigator called it this Lazarus-like effect. It was just really dramatic efficacy. And then to have the safety events that occurred. So they actually occurred within that first year of the acquisition. So we had the three patient deaths. Me and my organization became very, very much involved. In fact, Ed Conner, who had been the chief medical officer, he left after some of the deaths, but I stepped in as the kind of acting chief medical officer, we had another chief medical officer who was involved, and then we had a fourth death, and I became acting again for a period of time.

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Steve Paul, Karuna Therapeutics CEO (Third Rock)

Karuna's schiz­o­phre­nia drug pass­es a close­ly-watched PhI­II test, will head to FDA in mid-2023

An investigational pill that combines a former Eli Lilly CNS compound with an overactive bladder drug was better than placebo at reducing a scale of symptoms experienced by patients with schizophrenia in a Phase III trial.

Karuna Therapeutics’ drug passed the primary goal in EMERGENT-2, the Boston biotech said early Monday morning, alongside quarterly earnings. The study is the first of Karuna’s four Phase III clinical trials to read out in schizophrenia and will provide the backbone to the biotech’s first drug approval application, slated for mid-2023.

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