Covid-19 roundup: No­var­tis treat­ment comes up short in PhI­II; Hu­mani­gen ex­pands tri­al, but draws crit­i­cism

A ma­jor play­er try­ing to adapt an an­ti-in­flam­ma­to­ry for Covid-19 has seen the drug fall flat.

No­var­tis re­port­ed Fri­day that a Phase III tri­al eval­u­at­ing canakinum­ab in hos­pi­tal­ized Covid-19 cas­es with pneu­mo­nia and cy­tokine re­lease syn­drome did not meet its pri­ma­ry end­point. The in­ter­im analy­sis showed that the drug did not im­prove the chance of sur­vival with­out the need for ven­ti­la­tors com­pared to the con­trol group.

Ad­di­tion­al­ly, the study failed to meet the sec­ondary end­point of re­duc­ing mor­tal­i­ty rates af­ter four weeks of stop­ping treat­ment.

John Tsai

“Though the … tri­al did not show the pa­tient ben­e­fit we were hop­ing for, it helps im­prove the sci­en­tif­ic un­der­stand­ing of COVID-19 and the role of in­ter­leukin-1β in­hi­bi­tion,” No­var­tis CMO John Tsai said in a state­ment.

Re­searchers stud­ied canakinum­ab on top of stan­dard of care against the stan­dard of care with place­bo. For the pri­ma­ry, canakinum­ab demon­strat­ed 88.8% sur­vival with­out ven­ti­la­tion com­pared to 85.7% in the con­trol, good for a p-val­ue of 0.29. In the sec­ondary, the mor­tal­i­ty rate in the drug arm was 4.9% against 7.2% for place­bo, giv­ing a 0.33 p-val­ue. There were no new safe­ty is­sues.

Canakinum­ab was first ap­proved in 2009 and is sold un­der the brand name Ilaris. An IL-1 be­ta in­hibitor, the drug is in­di­cat­ed in sev­er­al rare con­di­tions, in­clud­ing pe­ri­od­ic fever syn­dromes, adult-on­set Still’s dis­ease and sys­temic ju­ve­nile id­io­path­ic arthri­tis.

The land­scape for Covid-19 treat­ments is scarce, with on­ly one ther­a­py cur­rent­ly ful­ly ap­proved by the FDA — Gilead’s Vek­lury. That drug, al­so known as remde­sivir, was giv­en the green light de­spite a large WHO-backed study say­ing it had lit­tle to no ef­fect in short­en­ing hos­pi­tal stays, im­prov­ing mor­tal­i­ty rates or re­duc­ing the num­ber of pa­tients need­ing ven­ti­la­tors.

Re­gen­eron and Eli Lil­ly are work­ing on their own Covid-19 treat­ments as well, and No­var­tis con­tin­ues to study rux­oli­tinib in the dis­ease with re­sults from a Phase III ex­pect­ed by the end of the year. — Max Gel­man

For­mer Shkre­li out­let Hu­mani­gen re­leas­es pos­i­tive in­ter­pre­ta­tion of blind­ed da­ta af­ter DSMB rec­om­mends tri­al ex­pan­sion

Hu­mani­gen, one of “Phar­ma Bro” Mar­tin Shkre­li’s for­mer com­pa­nies, al­so spot­light­ed re­sults from a Covid-19 treat­ment study for their ex­per­i­men­tal drug lenzilum­ab.

How­ev­er, con­cerns arose from out­side an­a­lysts about the na­ture of how Hu­mani­gen $HGEN ar­rived at its re­sults. Ac­cord­ing to a re­port from STAT News, two ex­perts in clin­i­cal tri­al sta­tis­tics said that Hu­mani­gen’s dis­clo­sure of the re­sults is not ap­pro­pri­ate giv­en that the com­pa­ny has not ac­tu­al­ly seen any of the da­ta.

Hu­mani­gen is con­duct­ing an “adap­tive tri­al,” which al­lows a study to be ex­pand­ed at a cer­tain point should the DSMB rec­om­mend it do so. In this in­stance, the DSMB rec­om­mend­ed the tri­al ex­pand from 257 ex­pect­ed im­prove­ments to 402, and Hu­mani­gen re­verse-en­gi­neered that rec­om­men­da­tion to es­ti­mate that the lenzilum­ab arm of the tri­al re­sult­ed in 37% more re­cov­er­ies.

“Adap­tive tri­als are de­signed to keep this kind of in­for­ma­tion away from the spon­sor and, in par­tic­u­lar, away from the pub­lic and re­leas­ing it in this fash­ion can cause op­er­a­tional bias and jeop­ar­dize the in­tegri­ty of the study,” Kert Viele, di­rec­tor of mod­el­ing and sim­u­la­tion at top firm Berry Con­sul­tants, told STAT.

Viele added that re­leas­ing such an in­ter­pre­ta­tion could put reg­u­la­to­ry ap­provals at risk. Hu­mani­gen said it ex­pects to ap­ply for a EUA in the first quar­ter of next year.

De­spite the re­sults, in­vestors seemed ex­cit­ed at the news. Hu­mani­gen’s stock price shot up about 10% in ear­ly Fri­day trad­ing.

Lenzilum­ab, a GM-CSF mon­o­clon­al an­ti­body, is be­ing stud­ied to treat over­ac­tive im­mune re­spons­es seen in graft-ver­sus-host dis­ease and CAR-T can­cer ther­a­pies. Back in 2015, Shkre­li and an in­vest­ment group bought a ma­jor­i­ty stake in the com­pa­ny, then known as Kalo­Bios. When Shkre­li was ar­rest­ed for se­cu­ri­ties fraud, Kalo­Bios fired him, de­clared bank­rupt­cy and re-emerged as Hu­mani­gen in 2016. — Max Gel­man

As­pirin to be stud­ied in UK’s large RE­COV­ERY tri­al

A com­mon over-the-counter drug is now be­ing stud­ied to treat Covid-19 cas­es.

UK re­searchers are look­ing at whether or not as­pirin can re­duce the risk of blood clots in in­di­vid­u­als with Covid-19. The drug, an an­ti-in­flam­ma­to­ry and blood thin­ner, will be in­clud­ed in the large RE­COV­ERY tri­al eval­u­at­ing sev­er­al po­ten­tial Covid-19 treat­ments, the sci­en­tists said Fri­day.

More than 2,000 pa­tients are ex­pect­ed to re­ceive a dai­ly 150 mg as­pirin pill as part of the study, on top of the stan­dard of care. The re­sults will be com­pared to the stan­dard of care alone, and re­searchers will be look­ing at whether the drug im­proves mor­tal­i­ty rates af­ter four weeks.

The ra­tio­nale for adding the drug to the tri­al stems from over­ac­tive platelet ac­tiv­i­ty in those with the dis­ease, lead­ing to a high­er risk of clots.

“We felt it was par­tic­u­lar­ly im­por­tant to add as­pirin to the tri­al since there is a clear ra­tio­nale for be­liev­ing that it might be ben­e­fi­cial and it is safe, in­ex­pen­sive and wide­ly avail­able,” said Pe­ter Hor­by, co-chief of RE­COV­ERY, in a state­ment. “We are look­ing for med­i­cines for COVID-19 that can be used im­me­di­ate­ly by any­one, any­where in the world. We do not know if as­pirin is such a med­i­cine but we will find out.”

Re­searchers cau­tioned that it may take sev­er­al months to know if as­pirin has any sub­stan­tial ef­fect in treat­ing Covid-19. The oth­er drugs in the study are Azithromycin, Tocilizum­ab, con­va­les­cent plas­ma and Re­gen­eron’s ex­per­i­men­tal an­ti­body cock­tail. — Max Gel­man

A Swiss start­up rais­es $15.5M to rush an­ti­body in­to clin­ic

One of the lead­ing neu­tral­iz­ing an­ti­bod­ies now in clin­i­cal tri­als for Covid-19 emerged out of Switzer­land. Now, a new Swiss start­up thinks they can build a bet­ter one.

Memo Ther­a­peu­tics, a small biotech based out­side of Zurich, an­nounced to­day that they’ve raised a CHF 14 mil­lion ($15.5M) Se­ries B to push for­ward a Covid-19 neu­tral­iz­ing an­ti­body in­to the clin­ic by the win­ter. The round was led by the Swiss-fo­cused in­vest­ment fund Swiss­canto In­vest and the Swiss bank Zürcher Kan­ton­al­bank.

Karsten Fis­ch­er

The com­pa­ny was found­ed in 2016 around a mi­croflu­idics an­ti­body-dis­cov­ery plat­form, said Memo CEO and co-founder Karsten Fis­ch­er, and they’ve spent much of the last cou­ple years de­vel­op­ing an an­ti­body against BK virus, a pathogen that threat­ens pa­tients who re­ceive re­nal trans­plants. Like many com­pa­nies, though, they piv­ot­ed to Covid-19 af­ter the virus.

Like Eli Lil­ly’s part­ner Ab­Cellera and Vir Biotech­nol­o­gy, Memo us­es mi­croflu­idic tech­nol­o­gy to draw an­tivi­ral an­ti­bod­ies from re­cov­ered pa­tients. But Fis­ch­er says their tech­nol­o­gy al­lows them to keep and as­sess a much larg­er share of B cells and an­ti­bod­ies, giv­ing them greater free­dom to pick out the best one.

“You can com­pare it to a book: The oth­ers take a book and look in­side the book for ABC, and this book burns,” Fis­ch­er told End­points News. “We make a copy of the en­tire book.”

It’s an im­pos­si­ble claim to eval­u­ate as, like many biotechs, Memo has pub­lished lit­tle to prove their plat­form is su­pe­ri­or. Still, Covid-19 has rapid­ly ac­cel­er­at­ed plen­ty of com­pa­nies from ear­ly stage to clin­i­cal da­ta stage, so Memo may have a chance to prove it soon, with a Phase I set to be­gin in Feb­ru­ary. Mean­while, in BK virus, they’ll com­pete against Am­plyx, which re­cent­ly li­censed a Phase II an­ti­body from No­var­tis.   — Ja­son Mast

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

Da­ta Lit­er­a­cy: The Foun­da­tion for Mod­ern Tri­al Ex­e­cu­tion

In 2016, the International Council for Harmonisation (ICH) updated their “Guidelines for Good Clinical Practice.” One key shift was a mandate to implement a risk-based quality management system throughout all stages of a clinical trial, and to take a systematic, prioritized, risk-based approach to clinical trial monitoring—on-site monitoring, remote monitoring, or any combination thereof.

Mer­ck scraps Covid-19 vac­cine pro­grams af­ter they fail to mea­sure up on ef­fi­ca­cy in an­oth­er ma­jor set­back in the glob­al fight

After turning up late to the vaccine development game in the global fight against Covid-19, Merck is now making a quick exit.

The pharma giant is reporting this morning that it’s decided to drop development of 2 vaccines — V590 and V591 — after taking a look at Phase I data that simply don’t measure up to either the natural immune response seen in people exposed to the virus or the vaccines already on or near the market.

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Stéphane Bancel, Moderna CEO (Steven Ferdman/Getty Images)

Covid-19 roundup: Mod­er­na dou­bles down on Covid-19 with new boost­er tri­als; Aus­tralia plans do­mes­tic pro­duc­tion of As­traZeneca vac­cine amid dis­tri­b­u­tion lag

As Merck bows out of the global race to develop vaccines for Covid-19, Moderna is doubling down to make sure they can quell new variants that have recently emerged and quickly spread.

The Cambridge, MA-based biotech put out word on Monday that in vivo studies indicate their mRNA vaccine works well enough against two strains first detected in the UK and South Africa. But with a six-fold reduction in neutralizing titers observed against the latter strain, the company is launching a new study of a booster version to make sure it can do the job.

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Matt Gline (L) and Vivek Ramaswamy

Scoop: Vivek Ra­maswamy is hand­ing the CEO job to a top lieu­tenant at Roivant — but he’s not ex­act­ly leav­ing the biotech scene

Over the past 7 years since founding Roivant, Vivek Ramaswamy has been a constant blur of biotech building motion.

He launched his first biotech with an Alzheimer’s drug he picked up cheap, and watched the experiment implode in one of the highest profile pivotal disasters seen in the last decade. But it didn’t slow the 30-something exec down; if anything, he hit the accelerator. Ramaswamy blazed global paths and went on to raise billions to spur the creation of a large lineup of little Vants promising big things at a fast pace. He sold off a section of the Vant brigade to Sumitomo Dainippon for $3 billion. And more recently the relentless dealmaker has been building a computational discovery arm to add an AI-driven approach to kicking up new programs and companies, supplementing the in-licensing drive while pursuing advances that have created more than 700 jobs at Roivant, with $2 billion in reserves.

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Ron Cooper, Albireo CEO

Al­bireo just ad­vanced down to the 10-yard line at the FDA. And Ron Coop­er’s team is get­ting prepped for the next big play

When Albireo Pharma’s board $ALBO moved to bring in Ron Cooper as the CEO more than 5 years ago, the development-stage company went with an experienced commercial player who had a big-time position on his resume after running Bristol Myers’ commercial ops in Europe.

Now, after successfully navigating a pivotal study, putting them in a foot race with a rival toward an FDA OK, Cooper is getting a boost from regulators on the last drive back to an arena he understands completely.

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Hal Barron, GSK via YouTube

What does $29B buy you in Big Phar­ma? In Glax­o­SmithK­line’s case, a whole lot of un­com­fort­able ques­tions about the pipeline

Talk about your bad timing.

A little over a week ago, GSK R&D chief Hal Barron marked his third anniversary at the research helm by taking a turn at the virtual podium during JP Morgan to make the case that he and his team had built a valuable late-stage pipeline capable of churning out more than 10 blockbusters in the next 5 years.

And then, just days later, one of the cancer drugs he bet big on as a top prospect — bintrafusp, partnered with Merck KGaA — failed its first pivotal test in non-small cell lung cancer.

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Can strug­gling Iterum turn the cor­ner to an an­tibi­ot­ic suc­cess sto­ry? They will know in six months

More than five years after Corey Fishman and Michael Dunne dusted sulopenem off Pfizer’s shelves — the second castoff antibiotic they’ve brought out of the pharma giant — and founded Iterum Therapeutics around that single drug, they have lined up a quick shot at approval with priority review from the FDA.

The decision, six months from now, will mark a make-or-break moment for a struggling biotech that has just enough cash to keep the lights on until the third quarter.

Bahija Jallal, Immunocore

Buried in Im­muno­core's IPO fil­ings? A kick­back scheme from a now for­mer em­ploy­ee

Immunocore spent much of 2019 dealing with the fallout of the Neil Woodford scandal, as the former star investor’s fall crashed the biotech’s valuation out of unicorn range. Now it turns out that the company spent 2020 dealing with another internal scandal.

The longtime UK biotech darling disclosed in their IPO filing last week that they had fallen victim to an alleged kickback scheme involving one of their employees. After a whistleblower came forward, they said in their F-1, they spent the summer and spring investigating, finding fraud on the part of an employee and two outside vendors.

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Lon­za look­ing to build on 'd­if­fer­en­ti­at­ed ad­van­tage' in Covid-19, CD­MO mar­ket­place in 2021

It’s not new for Lonza, the Swiss CDMO nearing its quasquicentennial anniversary, to be in the upper echelon of the biotech manufacturing industry.

But 2020 — as it was for many CDMOs — was a special year even by Lonza’s standards. The company inked a deal to produce 1 billion worldwide doses of Moderna’s Covid-19 vaccine and tapped pharma vet Pierre-Alain Ruffieux to lead its operations, moves which have allowed Lonza to make a myriad of other deals that will continue to ramp up its global production capacity.