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

Paul Hudson, Getty Images

UP­DAT­ED: Sanofi CEO Hud­son lays out new R&D fo­cus — chop­ping di­a­betes, car­dio and slash­ing $2B-plus costs in sur­gi­cal dis­sec­tion

Earlier on Monday, new Sanofi CEO Paul Hudson baited the hook on his upcoming strategy presentation Tuesday with a tell-tale deal to buy Synthorx for $2.5 billion. That fits squarely with hints that he’s pointing the company to a bigger future in oncology, which also squares with a major industry tilt.

In a big reveal later in the day, though, Hudson offered a slate of stunners on his plans to surgically dissect and reassemble the portfoloio, saying that the company is dropping cardio and diabetes research — which covers two of its biggest franchise arenas. Sanofi missed the boat on developing new diabetes drugs, and now it’s pulling out entirely. As part of the pullback, it’s dropping efpeglenatide, their once-weekly GLP-1 injection for diabetes.

“To be out of cardiovascular and diabetes is not easy for a company like ours with an incredibly proud history,” Hudson said on a call with reporters, according to the Wall Street Journal. “As tough a choice as that is, we’re making that choice.”

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Cor­re­vio is putting it­self up on the auc­tion block af­ter FDA re­view pan­el points to an­oth­er re­jec­tion

For 13 years, the Canadian biotech Correvio tried to get the FDA to accept a heart drug since abandoned by Merck and Astellas. Yesterday, the agency’s outside experts voted 11-2 against approval, all but assuring another rejection for the atrial fibrillation compound vernakalant.

And today Correvio announced that Correvio may soon be no more. The company said it is looking to sell itself as its stock plummets into penny-stock territory $CORV and its potential moneymaker sputters once more.

Psilocybin mushrooms (via The Denver Post)

In a key step for psy­che­del­ic re­search, mag­ic mush­room com­pound clears first clin­i­cal safe­ty hur­dle

Exasperated with the often-ineffective existing slate of antidepressants, COMPASS Pathways set up shop in London 2016 — and made a beeline for psilocybin, the psychoactive ingredient in magic mushrooms.

On Wednesday, the startup said its man-made version of the chemical — which is illegal across geographies in its natural fungi form — had been well-tolerated in an early-stage, placebo-controlled trial in 89 healthy volunteers.

Al­pham­ab On­col­o­gy rounds out HKEX's sec­ond biotech IPO year with $230M raise and high lo­cal in­ter­est

Alphamab Oncology has inspired a surge of local interest in what will likely be the Hong Kong Stock Exchange’s last biotech run of the year, pricing its IPO on the high end of the range and raising over $230 million (HK$1.83 billion).

After rejigging the offering structure and making up to 50% available for enthusiastic local investors, the biotech sold 179.4 million shares at $1.31 (HK$10.2) and saw its stock rise to $1.77 ($13.8) on the first day of trading.

For sale: Long-act­ing PhI­II GLP-1 di­a­betes drug that’s way be­hind ri­vals, now spurned by Sanofi

Almost exactly 4 years ago Sanofi came to the bargaining table with South Korea’s Hanmi bearing $434 million dollars in cash and offering about $4 billion in milestones to in-license their once-weekly GLP-1 injectable. The pact was intended to revive their ailing diabetes division. Instead, it turned into a very expensive grave to mark the end of Sanofi’s R&D ambitions in the field.

Sanofi CEO Paul Hudson used efpeglenatide’s demise — while committing to paying hundreds of millions of more dollars to push it through 5 late-stage studies — as a marker of the company’s determination to stay focused on first and best-in-class drugs.

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What does $6.9B buy these days in on­col­o­gy R&D? As­traZeneca has a land­mark an­swer

Given the way the FDA has been whisking through new drug approvals months ahead of their PDUFA date, AstraZeneca and their partners Daiichi Sankyo may not have to wait until Q2 of next year to get a green light on trastuzumab deruxtecan (DS-8201).

The pharma giant this morning played their ace in the hole, showing off why they were willing to commit to a $6.9 billion deal — with $1.35 billion in a cash upfront — to partner on the drug.

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Parkin­son's trans­plants emerge as stem cell pi­o­neer Jeanne Lor­ing joins R&D race

Jeanne Loring hadn’t studied Parkinson’s in 22 years when she got an email from a local neurologist.

The neurologist, Melissa Houser, didn’t know Loring had ever published on the disease. She was just looking for a stem cell researcher who might hear her out. 

“I think I was just picked out a hat,” Loring told Endpoints News. 

At a meeting in Loring’s Scripps Research office, Houser and a Parkinson’s nurse practitioner, Sherrie Gould, asked her why there was so much research done in stem cell transplants for other neurodegenerative diseases but not Parkinson’s. They wanted to know if she would work on one. 

Paul Hudson, Sanofi

Paul Hud­son promis­es a bright new fu­ture at Sanofi, kick­ing loose me-too drugs and fo­cus­ing on land­mark ad­vances. But can he de­liv­er?

Paul Hudson was on a mission Tuesday morning as he stood up to address Sanofi’s new R&D and business strategy.

Still fresh into the job, the new CEO set out to convince his audience — including the legions of nervous staffers inevitably devoting much of their day to listening in — that the pharma giant is shedding the layers of bureaucracy that had held them back from making progress in the past, dropping the duds in the pipeline and reprioritizing a more narrow set of experimental drugs that were promised as first-in-class or best-in-class.  The company, he added, is now positioned to “go after other opportunities” that could offer a transformational approach to treating its core diseases.

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Large advertisements for the drug Vivitrol decorate the walls of Grand Central Station on June 15, 2017 in New York City. (Photo: Andrew Lichtenstein via Getty)

FDA slaps down Alk­er­mes for mis­lead­ing Viv­it­rol ads — don't for­get vul­ner­a­bil­i­ty to opi­oid over­dose

The ads piqued interest as soon as they started appearing in 2016: at Grand Central Station, on the Red Line in Cambridge, and on a billboard off the New Jersey Turnpike. All showed a young person, generally with his or her arms crossed, and the question, “what is Vivitrol?”

Vivitrol’s maker, Alkermes, was in the midst of a marketing and lobbying campaign to promote the anti-opioid addiction drug — a campaign that would face significant backlash for tarnishing competitors despite little evidence for Vivitrol’s superiority.