Safe­ty fears spur FDA to pause check­point com­bo stud­ies by Bris­tol-My­ers, Cel­gene

Two months af­ter the FDA or­dered Mer­ck to slam the brakes on three Keytru­da com­bo stud­ies tar­get­ing mul­ti­ple myelo­ma, alarmed reg­u­la­tors have fol­lowed up by post­ing a stop sign on en­rolling any new pa­tients in Bris­tol-My­ers Squibb’s three ri­val stud­ies con­cen­trat­ing on the same dis­ease with the same com­bi­na­tion ap­proach­es. And hours lat­er Cel­gene $CELG added that it is be­ing forced to pause 5 com­bo stud­ies us­ing As­traZeneca’s Imfinzi while get­ting slammed with a full hold on one oth­er.

First to be of­fi­cial­ly frozen in place were Mer­ck’s KEYNOTE-183 and KEYNOTE-185 af­ter re­searchers spot­ted a high­er risk of death in the drug arms. Those mul­ti­ple myelo­ma tri­als matched Mer­ck’s block­buster ther­a­py with two drugs from Cel­gene: Po­m­a­lyst and its big drug Revlim­id. The FDA al­so or­dered pa­tients tak­en off of treat­ment in KEYNOTE-023 Co­hort 1, match­ing Keytru­da in com­bi­na­tion with lenalido­mide and dex­am­etha­sone in pa­tients who re­ceived pri­or an­ti-mul­ti­ple myelo­ma treat­ment with an im­munomod­u­la­to­ry (IMiD) treat­ment (lenalido­mide, po­ma­lido­mide or thalido­mide).

Wor­ried by ev­i­dence of safe­ty is­sues, the FDA fol­lowed up Wednes­day evening by or­der­ing a halt to en­roll­ment of new pa­tients in Bris­tol-My­ers’ stud­ies mar­ry­ing Op­di­vo with the same drugs: CA209602 (Check­Mate-602), CA209039 (Check­Mate-039) and CA204142 — al­so mul­ti­ple myelo­ma com­bo stud­ies.

At Cel­gene the dam­age is worse, with a full hold forc­ing re­searchers drop an ear­ly study look­ing at dur­val­um­ab in com­bi­na­tion with lenalido­mide with and with­out low-dose dex­am­etha­sone in mul­ti­ple myelo­ma pa­tients.

Com­bined, therse com­pa­nies have hun­dreds of com­bo stud­ies un­der­way, but reg­u­la­tors clear­ly be­lieve that there’s some oth­er threat to pa­tients in these par­tic­u­lar com­bi­na­tion stud­ies us­ing Cel­gene’s main­stay ther­a­pies. The FDA high­light­ed that con­cern just a week ago, care­ful­ly spelling out their rea­sons for sus­pend­ing the three Mer­ck stud­ies and point­ing out they were hunt­ing down and re­view­ing oth­er, sim­i­lar PD-(L)1 com­bos in the clin­ic.

Bris­tol-My­ers made for a nat­ur­al first stop in that process, with Cel­gene get­ting tagged at vir­tu­al­ly the same time.

The lat­est or­der from the FDA fol­lowed a stun­ning re­ver­sal for Cel­lec­tis, which was slammed with a clin­i­cal hold on Tues­day af­ter the first pa­tient treat­ed in its de­but off-the-shelf CAR-T study died, un­der­scor­ing the un­known risks that still con­front ad­vanced can­cer pa­tients sign­ing up for these ex­per­i­men­tal im­muno-on­col­o­gy tri­als.

Mer­ck and Bris­tol-My­ers are way out front with check­point in­hibitors Keytru­da and Op­di­vo as their PD-1 su­per­stars con­tin­ue to post jaw-drop­ping re­sults in can­cer. Clear­ly, though, as re­searchers con­tin­ue to test the bound­aries of what these new ther­a­pies can do un­ex­pect­ed safe­ty is­sues con­tin­ue to arise, rais­ing ques­tions of just how far de­vel­op­ers should take the drugs.

That same kind of safe­ty is­sue scut­tled Juno’s lead drug, which wound up killing three pa­tients last year af­ter the FDA pre­ma­ture­ly of­fered a green light to re­sume test­ing of its CAR-T af­ter a brief clin­i­cal hold. At this point, reg­u­la­tors ap­pear to be shift­ing their po­si­tion from an en­cour­ag­ing sig­nal to floor it, to a more cau­tious po­si­tion of study­ing safe­ty threats be­fore bar­rel­ing ahead.

For now, safe­ty is still a gray zone in im­muno-on­col­o­gy, as the da­ta con­tin­ues to pour in.

Here comes the oral GLP-1 drug for di­a­betes — but No­vo Nordisk is­n't dis­clos­ing Ry­bel­sus price just yet

Novo Nordisk’s priority review voucher on oral semaglutide has paid off. The FDA approval for the GLP-1 drug hit late Friday morning, around six months after the NDA filing.

Rybelsus will be the first GLP-1 pill to enter the type 2 diabetes market — a compelling offering that analysts have pegged as a blockbuster drug with sales estimates ranging from $2 billion to $5 billion.

Ozempic, the once-weekly injectable formulation of semaglutide, brought in around $552 million (DKK 3.75 billion) in the first half of 2019.

As Nas­daq en­rolls the fi­nal batch of 2019 IPOs, how have the num­bers com­pared to past years?

IGM Biosciences’ upsized IPO haul, coming after SpringWorks’ sizable public debut, has revved up some momentum for the last rush of biotech IPOs in 2019.

With 39 new listings on the books and roughly two more months to go before winding down, Nasdaq’s head of healthcare listings Jordan Saxe sees the exchange marking 50 to 60 biopharma IPOs for the year.

“December 15 is usually the last possible day that companies will price,” he said, as companies get ready for business talks at the annual JP Morgan Healthcare Conference in January.

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A fa­vorite in Alex­ion’s C-suite is leav­ing, and some mighty sur­prised an­a­lysts aren’t the least bit hap­py about it

Analysts hate to lose a biotech CFO they’ve come to trust and admire — especially if they’re being blindsided by a surprise exit.

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Oxitec biologist releases genetically modified mosquitoes in Piracicaba, Brazil in 2016 [credit: Getty Images]

In­trex­on unit push­es back against claims its GM mos­qui­toes are mak­ing dis­ease-friend­ly mu­tants

When the hysteria of Zika transmission sprang into the American zeitgeist a few years ago, UK-based Oxitec was already field-testing its male Aedes aegypti mosquito, crafted to possess a gene engineered to obliterate its progeny long before maturation.

But when a group of independent scientists evaluated the impact of the release of these genetically-modified mosquitoes in a trial conducted by Oxitec in Brazil between 2013 and 2015, they found that some of the offspring had managed to survive — prompting them to speculate what impact the survivors could have on disease transmission and/or insecticide resistance.

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Pur­due threat­ens to walk away from set­tle­ment, asks to pay em­ploy­ees mil­lions in bonus­es

There are two updates on the lawsuit against Purdue Pharma over its role in fueling the opioid epidemic, as the Sackler family threatens to walk away from their pledge to pay out $3 billion if a bankruptcy judge does not stop outstanding state lawsuits against them. At the same time, the company has asked permission to pay millions in bonuses to select employees.

Purdue filed for chapter 11 bankruptcy this week as part of its signed resolution to over 2,000 lawsuits. The deal would see the Sackler family that owns Purdue give $3 billion from their personal wealth and the company turned into a trust committed to curbing and reversing overdoses.

Aerial view of Genentech's campus in South San Francisco [Credit: Getty]

Genen­tech sub­mits a big plan to ex­pand its South San Fran­cis­co foot­print

The sign is still there, a quaint reminder of whitewashed concrete not 5 miles from Genentech’s sprawling, chrome-and-glass campus: South Francisco The Industrial City. 

The city keeps the old sign, first erected in 1923, as a tourist site and a kind of civic memento to the days it packed meat, milled lumber and burned enough steel to earn the moniker “Smokestack of the Peninsula.” But the real indication of where you are and how much has changed both in San Francisco and in the global economy since a couple researchers and investors rented out an empty warehouse 40 years ago comes in a far smaller blue sign, resembling a Rotary Club post, off the highway: South San Francisco, The Birthplace of Biotech.

While No­var­tis ban­ish­es Zol­gens­ma scan­dal scars — Bio­gen goes on a Spin­raza 'of­fen­sive'

While Novartis painstakingly works to mop up the stench of the data manipulation scandal associated with its expensive gene therapy for spinal muscular atrophy (SMA) Zolgensma— rival Biogen is attempting to expand the use of its SMA therapy, Spinraza. 

The US drugmaker $BIIB secured US approval for Spinraza for use in the often fatal genetic disease in 2016. The approval covered a broad range of patients with infantile-onset (most likely to develop Type 1) SMA. 

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Eye­ing big ther­a­peu­tic push, Gink­go bags $290M to build a cell pro­gram­ming em­pire

Ginkgo Bioworks is on a roll. Days after publicizing a plan to nurture new startups via partnerships with accelerators Y Combinator and Petri, the Boston biotech says it has raised another $290 million for its cell programming platform to reach further and wider.

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UP­DAT­ED: Speak­er Nan­cy Pelosi to un­veil bill for fed­er­al­ly ne­go­ti­at­ed drug prices

After months of buzz from both sides of the aisle, Speaker Nancy Pelosi will today introduce her plan to allow the federal government to negotiate prices for 250 prescription drugs, setting up a showdown with a pharmaceutical industry working overtime to prevent it.

The need to limit drug prices is a rare point of agreement between President Trump and Democrats, although the president has yet to comment on the proposal and will likely face pressure to back a more conservative option or no bill at all. Republican Senator Chuck Grassley is reportedly lobbying his fellow party members on a more modest proposal he negotiated with Democratic Senator Ron Wyden in July.