Af­ter falling short on pre­lim OS da­ta, EMA tells Aveo it wants to see some­thing bet­ter on its long suf­fer­ing ti­vo this sum­mer — or else

When Aveo On­col­o­gy scored Eu­ro­pean ap­proval in 2017 for its lead can­cer drug tivozanib — de­spite the treat­ment’s che­quered past — a come­back sto­ry was in the mak­ing. New piv­otal da­ta could now threat­en that ap­proval, and the com­pa­ny’s in­vestors are los­ing pa­tience.

In 2013, da­ta from the 517-pa­tient TI­VO-1 study test­ing tivozanib against so­rafenib in front­line pa­tients with ad­vanced re­nal cell car­ci­no­ma (RCC) showed pa­tients giv­en the Aveo drug did not live as long as those on so­rafenib (me­di­an OS of 28.8 months for tivozanib ver­sus 29.3 months for so­rafenib) — al­though the dif­fer­ence in over­all sur­vival was not sta­tis­ti­cal­ly sig­nif­i­cant (HR=1.245, p=0.105). How­ev­er, tivozanib did meet the main goal of sig­nif­i­cant­ly im­prov­ing pro­gres­sion-free sur­vival (PFS) by a me­di­an of 2.8 months (HR=0.797; P=0.042).

The FDA was not im­pressed. The agency’s can­cer czar Richard Paz­dur is­sued a scathing re­view of tivozanib, as­sert­ing that an ap­proval for a drug that could be tied to an in­creased risk of death would set a dan­ger­ous prece­dent. An out­right re­jec­tion fol­lowed.

Michael Bai­ley

In 2016, Aveo’s fresh faced man­age­ment agreed to fork over $4 mil­lion to set­tle SEC charges that were im­posed on the drug de­vel­op­er’s for­mer top ex­ec­u­tive team — which stepped down the pre­ced­ing year — for keep­ing se­cret the FDA’s de­mand for a new tivozanib study, to an­swer lin­ger­ing con­cerns over pa­tient deaths in TI­VO-1, in or­der to qual­i­fy for ap­proval.

Mean­while, the EMA was a lit­tle more gen­er­ous. In 2017, the EU sanc­tioned Aveo’s part­ner EU­SA Phar­ma ap­proval for tivozanib — but with a caveat that topline da­ta re­sults from the 351-pa­tient TI­VO-3 tri­al — eval­u­at­ing tivozanib against so­rafenib in RCC who have failed at least two pri­or reg­i­mens — would be pro­vid­ed as part of post-mar­ket­ing re­quire­ments.

Much like TI­VO-1, da­ta from TI­VO-3 un­veiled last No­vem­ber showed tivozanib in­duced a sta­tis­ti­cal­ly sig­nif­i­cant im­prove­ment in PFS (Me­di­an PFS was 5.6 months for tivozanib com­pared to 3.9 months for so­rafenib; HR=0.74; p=0.02). Months lat­er, Aveo pro­vid­ed pre­lim­i­nary OS da­ta that sug­gest­ed a non-sta­tis­ti­cal­ly sig­nif­i­cant dif­fer­ence in OS fa­vor­ing so­rafenib (HR=1.12, p=0.44).

On Wednes­day, Aveo in a fil­ing said the EMA has asked for the ad­di­tion­al in­ter­im OS analy­sis of TI­VO-3 by Au­gust 2019, and that “reg­u­la­to­ry ac­tion” will be con­sid­ered if a neg­a­tive OS trend is con­firmed. In ef­fect, if this OS trend is ce­ment­ed with ma­ture da­ta by Au­gust, Aveo could see its EU ap­proval re­scind­ed.

The Cam­bridge, Mass­a­chu­setts-based biotech’s shares $AVEO tum­bled near­ly 23% to $1.22 be­fore the bell.

Im­age: Shut­ter­stock

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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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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Noubar Afeyan, Flagship CEO and Tessera chairman (Victor Boyko/Getty Images)

Flag­ship ex­ecs take a les­son from na­ture to mas­ter ‘gene writ­ing,’ launch­ing a star-stud­ded biotech with big am­bi­tions to cure dis­ease

Flagship Pioneering has opened up its deep pockets to fund a biotech upstart out to revolutionize the whole gene therapy/gene editing field — before gene editing has even made it to the market. And they’ve surrounded themselves with some marquee scientists and execs who have crowded around to help shepherd the technology ahead.

The lead player here is Flagship general partner Geoff von Maltzahn, an MIT-trained synthetic biologist who set out in 2018 to do CRISPR — a widely used gene editing tool — and other rival technologies one or two better. Von Maltzahn has been working with Sana co-founder Jake Rubens, another synthetic biology player out of MIT who he describes as his “superstar,” who’s taken the CSO role.

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Shoshanna Shendelman, Applied Therapeutics CEO (Applied Therapeutics)

A lit­tle biotech slaps back at a 'crim­i­nal' short at­tack, vow­ing to pur­sue a pros­e­cu­tion of their case

As short attacks go, Biotech Research Partners’ assault on Applied Therapeutics’ “cherry picked” data and a variety of so-called red flags didn’t cause a whole lot of damage. Ahead of the July 4 holiday, its shares $APLT were dinged and showed signs of quick recovery.

But that didn’t stop an incendiary response, as the biotech swung into action bright and early Monday morning.

Applied Therapeutics accused the authors of the short report of manipulating graphs and figures, misrepresenting data and included factual misrepresentations — all of which added up, in their view, to fraud.

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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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Boehringer In­gel­heim ties the knot with Num­ab on new an­ti­bod­ies; Ca­balet­ta inks pact with Ar­ti­san

→ Switzerland’s Numab Therapeutics has added Boehringer Ingelheim to its roster of collaborators. And they will start with two projects aiming at developing new drugs for difficult-to-treat lung and gastrointestinal cancers and patients with geographic atrophy. “Numab’s technology platform fits well with our internal antibody discovery and engineering capabilities and will enhance our efforts to deliver transformative antibody-based therapeutics to patients,” said Paige Mahaney, an SVP at Boehringer Ingelheim.

David Hallal

AlloVir tests how much an an­tivi­ral biotech can reap in a pan­dem­ic stock mar­ket

The pandemic stock market has proven fruitful for virtually any type of biotech. Now a 7-year-old cell therapy startup will see how much it can yield for a company that specializes in fighting viruses.

AlloVir, a company that until 2019 largely lived off grant money, has filed for a $100 million IPO to back its line of off-the-shelf, virus-fighting T cells. Although in normal circumstances, $100 million could be a solid return for a biotech that got its first major round of funding only last year, we’ll have to wait to see how much the company ultimately earns. As Covid-19 has sent investor money scurrying to almost anyone in drug development, every single biotech to go public this year has prized above their midpoint or upsized their offering, according to Renaissance Capital, sometimes dramatically so.

Take­da’s post-merg­er deals con­tin­ue as OTC sub­sidiary is pre­pared for sale

Takeda has been burdened under mountains of debt since acquiring Shire for $62 billion 18 months ago, but one of the company’s biggest moves yet to relieve the stress could be on the horizon.

The Japanese pharma is preparing a bidding war for its $3.7 billion over-the-counter subsidiary, a sale that would dwarf previous spinoffs. Any transaction would be the latest in what’s been a long string of sell-offs, as Takeda marches unflinchingly toward its ultimate goal of shedding $10 billion in assets.

Cel­lec­tis slammed af­ter pa­tient dies and FDA slaps a hold on their tri­al for an off-the-shelf CAR-T for mul­ti­ple myelo­ma

Cellectis was slammed after the market close on Monday as the biotech reported that the FDA demanded it hit the brakes on their MELANI-01 trial for their off-the-shelf cell therapy UCARTCS1A after one of the patients in the study died of treatment-related cardiac arrest.

The multiple myeloma patient had previously been treated unsuccessfully with various therapies, noted the biotech, and had been given dose level two (DL2) of their allogeneic CAR-T.

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