Lil­ly's ap­proved can­cer drug Lartru­vo fails con­fir­ma­to­ry study, set­ting the stage for with­draw­al of reg­u­la­to­ry en­dorse­ment

Back in 2016, Lil­ly won FDA ac­cel­er­at­ed ap­proval for its soft tis­sue drug olara­tum­ab on the ba­sis of en­cour­ag­ing da­ta from a small 133-pa­tient mid-stage study, but on Fri­day a larg­er, con­fir­ma­to­ry tri­al meant to ce­ment the ap­proval showed that the treat­ment failed to help pa­tients live longer, which means the US health reg­u­la­tor can re­scind its en­dorse­ment of the drug.

The drug, sold as Lartru­vo, had won the FDA nod in com­bi­na­tion with the chemother­a­py dox­oru­bicin as a first-line treat­ment for a sub­set of pa­tients with the dis­ease, which had seen no new ap­provals in decades. By the third quar­ter of 2018, Lil­ly had raked in $221.2 mil­lion in Lartru­vo sales last year.

The con­fir­ma­to­ry Phase III tri­al — AN­NOUNCE — test­ed Lartru­vo in com­bi­na­tion with dox­oru­bicin, ver­sus dox­oru­bicin monother­a­py in pa­tients with ad­vanced or metasta­t­ic soft tis­sue sar­co­ma. The study did not meet the main goal of im­prov­ing over­all sur­vival in the pa­tient pop­u­la­tion, in­clud­ing the sub­set of leiomyosar­co­ma pa­tients — there was no dif­fer­ence in sur­vival be­tween the study arms for ei­ther pop­u­la­tion, the com­pa­ny said.

Anne White

Da­ta from the pre­vi­ous, pos­i­tive Phase II tri­al had helped Lil­ly se­cure ac­cel­er­at­ed ap­proval in the Unit­ed States, and con­di­tion­al ap­proval in Eu­rope. But those ap­provals were con­tin­gent on fa­vor­able AN­NOUNCE re­sults con­firm­ing its ben­e­fit, and now the com­pa­ny will talk to reg­u­la­tors to de­ter­mine the next steps for the drug.

For now, the drug­mak­er has sus­pend­ed Lartru­vo pro­mo­tion, and ex­pects to in­cur a pre-tax charge in the range of $70 mil­lion to $90 mil­lion (or $0.10 per share, af­ter tax) in the first quar­ter of 2019.

“Lil­ly was sur­prised and dis­ap­point­ed that LARTRU­VO did not im­prove sur­vival for pa­tients with ad­vanced soft tis­sue sar­co­ma in this study,” said Anne White, pres­i­dent of Lil­ly On­col­o­gy in a state­ment. Lil­ly’s $LLY shares slipped about 3% pre-mar­ket.

The drug is cur­rent­ly al­so be­ing test­ed in com­bi­na­tion with gem­c­itabine and do­c­etax­el in a sep­a­rate Phase II tri­al in ad­vanced soft tis­sue sar­co­ma pa­tients.

The fail­ure fol­lows Lil­ly’s an­nounce­ment this month to swal­low Loxo On­col­o­gy for $8 bil­lion. Ac­cord­ing to a SEC fil­ing post­ed on Thurs­day, Lil­ly ex­ec­u­tives were look­ing for a swift deal when they sat down with Loxo CEO Josh Bilenker five days ahead of Christ­mas. They were will­ing to fork out $230 a share for the small­er com­pa­ny, in a hur­ry to get the deal done in time for the JP­Mor­gan ex­trav­a­gan­za. There were no oth­ers bid­ders for the com­pa­ny, but in or­der to has­ten the buy­out, Lil­ly agreed even­tu­al­ly to pay $235 per Loxo share, al­low­ing for the ac­qui­si­tion to be re­vealed on Jan­u­ary 7.

UP­DAT­ED: Mer­ck pulls Keytru­da in SCLC af­ter ac­cel­er­at­ed nod. Is the FDA get­ting tough on drug­mak­ers that don't hit their marks?

In what could be an early shot in the battle against drugmakers that whiff on confirmatory studies to support accelerated approvals, the FDA ordered Bristol Myers Squibb late last year to give up Opdivo’s approval in SCLC. Now, Merck is next on the firing line — are we seeing the FDA buckling down on post-marketing offenders?

Merck has withdrawn its marketing approval for PD-(L)1 inhibitor Keytruda in metastatic small cell lung cancer as part of what it describes as an “industry-wide evaluation” by the FDA of drugs that do not meet the post-marketing checkpoints on which their accelerated nods were based, the company said Monday.

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Paul Sekhri

The next big biotech su­per­star? Paul Sekhri has some thoughts on that

It occasionally occurs to Paul Sekhri that if they pull this off, his company will be on the front page of the New York Times and a lead story in just about every major news outlet on the planet. He tries not to dwell on it, though.

“I just want to be laser-focused on getting to that point,” Sekhri says, before acknowledging, “Yes, it absolutely crossed my mind.”

Sekhri, a longtime biopharma executive with tenures at Sanofi and Novartis, is now entering year three as CEO of eGenesis, the biotech that George Church protégé Luhan Yang founded to genetically alter pigs so that they can be used for organ transplants. He led them through one megaround and has just closed another, raising $125 million from 17 different investors to push the first-ever (humanized) pig to human transplants into the clinic.

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Amit Munshi, Arena

One of Are­na's top drugs flops in a PhI­Ib study for IBS pain. But re­searchers tease out a pos­si­ble path for­ward as CEO ex­plores 's­trate­gic op­tion­s'

Four years ago, when Arena CEO Amit Munshi cut its ties to a troubled weight drug and doubled down on the pipeline, a cannabinoid receptor 2 agonist figured prominently in the biotech’s future. On Tuesday evening, however, Munshi’s high hopes for the drug took a nasty hit after it failed a Phase IIb study for patients with irritable bowel syndrome pain.

Put through a randomized pace with 273 patients, researchers said it flat failed the primary endpoint among the large group with abdominal pain. But they quickly went on to highlight subgroup data, always a tricky and controversial ploy, where they spotlighted a positive p value for patients with moderate to severe pain who received the high dose of the drug — one of 3 provided in the study.

Bob Nelsen (Photo by Michael Kovac/Getty Images)

With stars aligned and cash in re­serve, Bob Nelsen's Re­silience plans a makeover at 2 new fa­cil­i­ty ad­di­tions to its drug man­u­fac­tur­ing up­start

Bob Nelsen’s new, state-of-the-art drug manufacturing initiative is taking shape.

Just 3 months after gathering $800 million of launch money, a dream team board and a plan to shake up a field where he found too many bottlenecks and inefficiencies for the era of Covid-19, Resilience has snapped up a pair of facilities now in line for a retooling.

The company has acquired a 310,000-square-foot plant in Boston from Sanofi along with a 136,000-square-foot plant in Ontario to add to a network which CEO Rahul Singhvi says is just getting started on building his company’s operations up. The Sanofi deal comes with a contract to continue manufacturing one of its drugs.

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CEO Marco Taglietti (Scynexis)

'N­ev­er been more ur­gent:' Scynex­is looks to tack­le su­per­bug cri­sis with late-stage read­out for an­ti­fun­gal hope­ful

As the superbug crisis heats up around the world, Scynexis says it has new data from two interim analyses that prove its antifungal has the potential to treat a broad range of infections.

“The need for new anti-infectives capable of fighting the most resistant pathogens has never been more urgent as we confront the ongoing COVID-19 global pandemic,” CEO Marco Taglietti said in a statement.

A spot­light schiz­o­phre­nia drug in Neu­ro­crine's $2B Take­da deal flunks its first ma­jor test. But it's not giv­ing up yet

When Takeda spun out a pipeline of experimental psychiatry drugs to Neurocrine in a $2 billion deal amid a post-merger shakeout, R&D chief Andy Plump described the therapies as “very interesting but still difficult.”

On Tuesday, we got some idea of how difficult.

San Diego-based Neurocrine revealed that one of the three spotlight clinical programs they’d acquired failed the primary endpoint in a Phase II trial for schizophrenia, registering a negative outcome on the change from baseline in the positive and negative syndrome scale/negative symptom factor score (PANSS NSFS).

Af­ter bail­ing on Covid-19 vac­cines, Mer­ck will team up with J&J to pro­duce its shot as part of un­usu­al Big Phar­ma pact

Merck took a big gamble when it opted to jump into the Covid-19 vaccine race late, and made an equally momentous decision to back out in late January. Now, looking to chip in on the effort, Merck reportedly agreed to team up with one of the companies that has already crossed the finish line.

President Joe Biden on Tuesday is expected to announce a partnership between drugmakers Merck and Johnson & Johnson to jointly produce J&J’s recombinant protein Covid-19 vaccine that received the FDA’s emergency use authorization Saturday, the Washington Post reported.

Ab­b­Vie tees up a biotech buy­out af­ter siz­ing up their Parkin­son's drug spun out of Ke­van Shokat's lab

AbbVie has teed up a small but intriguing biotech buyout after looking over the preclinical work it’s been doing in Parkinson’s disease.

The company is called Mitokinin, a Bay Area biotech spun out of the lab of UCSF’s Kevan Shokat, whose scientific explorations have formed the academic basis of a slew of startups in the biotech hub. One of Shokat’s PhD students in the lab, Nicholas Hertz, co-founded Mitokinin using their lab work on PINK1 suggesting that amping up its activity could play an important role in regulating the mitochondrial dysfunction contributing to Parkinson’s disease pathogenesis and progression.

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Fi­bro­Gen shares skid low­er as a sur­prise ad­comm rais­es risks on roxa OK

FibroGen will likely have to delay its US rollout for roxadustat once again.

In an unexpected move, the FDA is convening its Cardiovascular and Renal Drugs Advisory Committee to review the NDA in an advisory committee meeting. The date is yet to be confirmed.

Just a few weeks ago, SVB Leerink analyst Geoffrey Porges predicted that the roxa approval could come ahead of the PDUFA date on March 20 — effusive despite already being let down once by the FDA’s extension of its review back in December. AstraZeneca, which is partnered with FibroGen on the chronic kidney disease-related anemia drug, disclosed regulators had requested further clarifying analyses of clinical data.