Déjà vu for Zaf­gen: Still fret­ting about lin­ger­ing car­dio con­cerns, FDA clamps a hold on lead obe­si­ty drug -- shares plunge

Two years af­ter Zaf­gen torched its lead obe­si­ty com­pound fol­low­ing an ug­ly crash in late-stage test­ing that cost lives, the FDA is still fret­ting whether the com­pa­ny is con­tin­u­ing to ex­pose more peo­ple to harm.

The biotech re­port­ed to­day that the FDA has slapped a clin­i­cal hold on their MetAP2 drug ZGN-1061, wor­ried that the car­dio threat posed by their first-gem drug be­lo­ranib might still be in play. They plan to fol­low up with a face-to-face meet­ing, but there’s no clar­i­ty on how long their drug could be in lim­bo now.

In­vestors hat­ed the sound of it. Zaf­gen’s shares cratered, plung­ing 46% short­ly af­ter the mar­ket opened Mon­day.

Zaf­gen’s shares $ZFGN — once over $40 — nev­er re­vived af­ter the plunge that oc­curred in the fall of 2015, when man­age­ment ini­tial­ly stonewalled in­vestors clam­or­ing to find out what had prompt­ed the com­pa­ny to abrupt­ly drop out of a promi­nent in­vest­ment con­fer­ence. Back-to-back deaths, though, along with a clin­i­cal hold that led to a list of re­quire­ments for be­lo­ranib’s clin­i­cal de­vel­op­ment that Zaf­gen de­cid­ed had cre­at­ed a hur­dle too steep to clear, killed that ef­fort.

Ac­cord­ing to their state­ment, Zaf­gen got the lat­est hold let­ter some­time last week.

The FDA cit­ed the pos­si­bil­i­ty of car­dio­vas­cu­lar (CV) safe­ty risk based on the Com­pa­ny’s pri­or com­pound and out­lined mul­ti­ple po­ten­tial paths for mov­ing for­ward, in­clud­ing non­clin­i­cal or clin­i­cal op­tions, to ad­dress these con­cerns in the on­go­ing de­vel­op­ment of ZGN-1061. The Com­pa­ny plans to as­sess these op­tions and re­quest a Type A meet­ing with the Agency to dis­cuss next steps with the pro­gram.

Tom Hugh­es

De­spite the reg­u­la­to­ry con­cerns in the US, Zaf­gen says it plans to sol­dier on with a dose-es­ca­lat­ing Phase II study for ZGN-1061 in Eu­rope, which is be­yond the FDA’s reach.

Like their first drug be­lo­ranib, ZGN-1061 has demon­strat­ed an abil­i­ty to knock off a sig­nif­i­cant amount of weight. But the safe­ty bar for a drug now guid­ed to­ward di­a­betes is clear­ly very high.

Leerink’s Joseph Schwartz had this to say af­ter the news hit:

As we pre­vi­ous­ly high­light­ed in de­tail, pre­clin­i­cal da­ta sug­gests that ZGN-1061 has the po­ten­tial to in­duce clot­ting fac­tors if it is not cleared. De­spite a clean safe­ty re­port card to date in a small Ph.2 study, our main con­cerns have stemmed from lack of dis­clo­sure about how the drug is me­tab­o­lized and cleared, and the po­ten­tial for drug-drug in­ter­ac­tions that could de­lay the drug’s clear­ance when test­ed in a larg­er Ph.3 study of T2D pa­tients, which we be­lieve could have played in­to the FDA’s de­ci­sion. How this de­ci­sion will af­fect the over­all time­line for this pro­gram is un­known, but the com­pa­ny plans on defin­ing a path for­ward with reg­u­la­tors.

Over the last few months Zaf­gen has seen a big change at the top, with Tom Hugh­es leav­ing the com­pa­ny af­ter lead­ing it for 9 years — to take the CEO’s job at Nav­i­tor — just ahead of board mem­ber Bruce Booth. 

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.

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.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 60,200+ biopharma pros reading Endpoints daily — and it's free.

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.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 60,200+ biopharma pros reading Endpoints daily — and it's free.

[via AP Images]

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.

David Grainger [file photo]

'Dis­con­nect the bas­tard­s' — one biotech's plan to break can­cer cell­s' uni­fied de­fens­es

Chemotherapy and radiotherapy are the current gladiators of cancer treatment, but they come with well-known limitations and side-effects. The emergence of immunotherapy — a ferocious new titan in oncologist’s toolbox — takes the brakes off the immune system to kill cancer cells with remarkable success in some cases, but the approach is not always effective. What makes certain forms of cancer so resilient? Scientists may have finally pieced together a tantalizing piece of the puzzle, and a new biotech is banking on a new approach to fill the gap.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 60,200+ biopharma pros reading Endpoints daily — and it's free.

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.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 60,200+ biopharma pros reading Endpoints daily — and it's free.

Scott Gottlieb, AP Images

Scott Got­tlieb is once again join­ing a team that en­joyed good times at the FDA un­der his high-en­er­gy stint at the helm

Right after jumping on Michael Milken’s FasterCures board on Monday, the newly departed FDA commissioner is back today with news about another life sciences board post that gives him a ringside chair to cheer on a lead player in the real-world evidence movement — one with very close ties to the FDA.

Aetion is reporting this morning that Gottlieb is joining their board, a group that includes Mohamad Makhzoumi, a general partner at New Enterprise Associates, where Gottlieb returned after stepping out of his role at the FDA 2 years after he started.

Gottlieb — one of the best connected execs in biopharma — knows this company well. As head of FDA he championed the use of real-world evidence to help guide drug developers and the agency in gaining greater efficiencies, which helped set up Aetion as a high-profile player in the game.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 60,200+ biopharma pros reading Endpoints daily — and it's free.

Tower Bridge in London [Shutterstock]

#UK­BIO19: Join GSK’s Hal Bar­ron and a group of top biotech ex­ecs for our 2nd an­nu­al biotech sum­mit in Lon­don

Over the past 10 years I’ve made a point of getting to know the Golden Triangle and the special role the UK biopharma industry plays there in drug development. The concentration of world class research institutes, some of the most accomplished scientists I’ve ever seen at work and a rising tide of global investment cash leaves an impression that there’s much, much more to come as biotech hubs are birthed and nurtured.