As­traZeneca gives it­self top marks for R&D pro­duc­tiv­i­ty makeover — but the ju­ry is still out

Is As­traZeneca a mod­el for Big Phar­ma R&D suc­cess?

Look­ing over their num­bers for Q3 last No­vem­ber, you’d be hard pressed to make that case. Five years af­ter they promised to turn around a deeply trou­bled com­pa­ny, CEO Pas­cal So­ri­ot and his ex­ec­u­tive crew were still on the de­fen­sive as they walked an­a­lysts through the lat­est slip­page on the prod­uct rev­enue side of the busi­ness. Prod­uct sales were down 3%, fol­low­ing an 11% drop in H1. And af­ter five years at the helm, So­ri­ot was still not say­ing when the great de­cline would end.

Mene Pan­ga­los

In­side the R&D or­ga­ni­za­tion, though, a group led by Mene Pan­ga­los — who heads the In­no­v­a­tive Med­i­cines and Ear­ly De­vel­op­ment unit at As­traZeneca — has stud­ied 11 years of pro­duc­tiv­i­ty num­bers for the phar­ma gi­ant. And in a thor­ough analy­sis pub­lished in Na­ture Re­views Drug Dis­cov­ery they say they’re now whip­ping the in­dus­try stan­dard on R&D pro­duc­tiv­i­ty af­ter strip­ping down the ear­ly-stage pipeline — qua­dru­pling their suc­cess rate.

Key­ing off of a re­or­ga­ni­za­tion launched in 2011, As­traZeneca’s team says they tracked a nom­i­na­tion-through-Phase III suc­cess rate of 4% for the five years pre­vi­ous, even worse than the aw­ful 5% in­dus­try av­er­age they cite from the Cen­tre for Med­i­cines Re­search. (There are no agreed up­on fig­ures here, with some es­ti­mates set at a 90% fail­ure rate, though every­one would agree that suc­cess rates on this stan­dard are re­mark­ably low.)

The suc­cess rate in Phase II was 15%, well un­der a 22% stan­dard, says the com­pa­ny.

At that point, As­traZeneca be­gan its own ver­sion of an R&D re­struc­tur­ing fo­cused on what it calls the 5R frame­work that cen­tered on the right tar­get, the right tis­sue, the right safe­ty, the right pa­tient and the right com­mer­cial po­ten­tial. It’s al­so re­drawn the bound­aries of R&D around four core fields.

And As­traZeneca al­so gives it­self a pat on the back on the big C — cul­ture.

Plac­ing em­pha­sis on ‘truth-seek­ing’ be­hav­iour and ask­ing the ‘killer’ ques­tions for a project have been a cru­cial part of our cul­tur­al change. We have con­tin­ued to push the theme of ‘right cul­ture’ by im­ple­ment­ing stronger quan­ti­ta­tive sci­ences and quan­ti­ta­tive de­ci­sion-mak­ing.

Pas­cal So­ri­ot

Af­ter slash­ing the num­ber of pro­grams go­ing in­to the clin­ic, As­traZeneca says that it’s been able to track a clear rise in pro­duc­tiv­i­ty, with their start-through-Phase III suc­cess rate for 2012 to 2016 jump­ing to 19%. The cost for a suc­cess­ful pro­gram has gone down sig­nif­i­cant­ly as well.

And to top it all off, the com­pa­ny says that in­dus­try an­a­lysts are tac­it­ly en­dors­ing their ap­proach, much more like­ly to of­fer a buy rat­ing on the stock.

So every­thing is great?

Not by half.

As­traZeneca has had some no­table wins, par­tic­u­lar­ly in on­col­o­gy. But some of those same bull­ish an­a­lysts have been grow­ing restive about So­ri­ot’s strat­e­gy of sell­ing off what he con­sid­ers non-core — or of­ten dis­ap­point­ing — as­sets. They would al­so like some clear ev­i­dence that the com­pa­ny has hit rock bot­tom and is com­ing back up, a hard test for any R&D pro­duc­tiv­i­ty stan­dard.

So­ri­ot built the sto­ry of the com­pa­ny’s prospects in can­cer around a com­bi­na­tion of two check­point in­hibitors, Imfinzi and treme­li­mum­ab, which failed the first leg of the piv­otal tri­al. And the ex­ec­u­tive team still faces a moun­tain­ous chal­lenge in hit­ting am­bi­tious rev­enue pro­jec­tions So­ri­ot set while fend­ing off a buy­out at­tempt by Pfiz­er.

So­ri­ot him­self nev­er de­nied he was se­ri­ous­ly con­sid­er­ing a leap to Te­va last year, which didn’t ex­act­ly look like an en­dorse­ment of the com­pa­ny’s R&D suc­cess.

As­traZeneca was the in­dus­try’s bas­ket case when So­ri­ot took over in 2012. It’s less so now. But no one is call­ing the makeover a clear suc­cess, yet.

Ex­cept for As­traZeneca.

And if in fact you can turn around the suc­cess rate in R&D and still fail to achieve the kind of near-term com­mer­cial suc­cess you need, what does that say about ROI in Big Phar­ma over­all?

Qual­i­ty Con­trol in Cell and Gene Ther­a­py – What’s Re­al­ly at Stake?

In early 2021, Bluebird Bio was forced to suspend clinical trials of its gene therapy for sickle cell disease after two patients in the trial developed cancer. As company scientists rushed to assess whether there was any causal link between the therapy and the cancer cases, Bluebird’s stock value plummeted – as did those of multiple other biopharma companies developing similar therapies.

While investigations concluded that the gene therapy was unlikely to have caused cancer, investors and the public may be more skittish regarding the safety of gene and cell therapies after this episode. This recent example highlights how delicate the fields of cell and gene therapy remain today, even as they show great promise.

Law pro­fes­sors call for FDA to dis­close all safe­ty and ef­fi­ca­cy da­ta for drugs

Back in early 2018 when Scott Gottlieb led the FDA, there was a moment when the agency seemed poised to release redacted complete response letters and other previously undisclosed data. But that initiative never gained steam.

Now, a growing chorus of researchers are finding that a dearth of public data on clinical trials and pharmaceuticals means industry and the FDA cannot be held accountable, two law professors from Yale and New York University write in an article published Wednesday in the California Law Review.

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Novavax CEO Stanley Erck at the White House in 2020 (Andrew Harnik, AP Images)

As fears mount over J&J and As­traZeneca, No­vavax en­ters a shaky spot­light

As concerns rise around the J&J and AstraZeneca vaccines, global attention is increasingly turning to the little, 33-year-old, productless, bankruptcy-flirting biotech that could: Novavax.

In the now 16-month race to develop and deploy Covid-19 vaccines, Novavax has at times seemed like the pandemic’s most unsuspecting frontrunner and at times like an overhyped also-ran. Although they started the pandemic with only enough cash to last 6 months, they leveraged old connections and believers into $2 billion and emerged last summer with data experts said surpassed Pfizer and Moderna. They unveiled plans to quickly scale to 2 billion doses. Then they couldn’t even make enough material to run their US trial and watched four other companies beat them to the finish line.

FDA of­fers scathing re­view of Emer­gent plan­t's san­i­tary con­di­tions, em­ploy­ee train­ing af­ter halt­ing pro­duc­tion

The FDA wrapped up its inspection of Emergent’s troubled vaccine manufacturing plant in Baltimore on Tuesday, after halting production there on Monday. By Wednesday morning, the agency already released a series of scathing observations on the cross contamination, sanitary issues and lack of staff training that caused the contract manufacturer to dispose of millions of AstraZeneca and J&J vaccine doses.

Brad Bolzon (Versant)

Ver­sant pulls the wraps off of near­ly $1B in 3 new funds out to build the next fleet of biotech star­tups. And this new gen­er­a­tion is built for speed

Brad Bolzon has an apology to offer by way of introducing a set of 3 new funds that together pack a $950 million wallop in new biotech creation and growth.

“I want to apologize,” says the Versant chairman and managing partner, laughing a little in the intro, “that we don’t have anything fancy or flashy to tell you about our new fund. Same team, around the same amount of capital, same investment strategy. If it ain’t broke, don’t fix it.”

But then there’s the flip side, where everything has changed. Or at least speeded into a relative blur. Here’s Bolzon:

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Emma Walmsley, GlaxoSmithKline CEO (Kevin Dietsch/Pool via CNP/Alamy)

Glax­o­SmithK­line hus­tles the 7th PD-1 past the fin­ish line with Jem­per­li. But how big will up­take be?

Everything came up sevens for GlaxoSmithKline on Thursday as the pharma notched the seventh PD-1 approval seven years after the first such drugs were OK’ed in Keytruda and Opdivo. But will it bring GSK good fortune?

The FDA granted accelerated approval to dostarlimab, to be branded Jemperli, to treat recurrent or advanced endometrial cancer in a specific subset of patients following platinum-based chemo. It’s a drug that came to GSK through its buyout of Tesaro, which it snapped up for $5.1 billion back in December 2018.

JP Gabriel, Ocugen

JP Gabriel watched from the bleach­ers as the pan­dem­ic raged. Now head of sup­ply chain at Ocu­gen, he's ready to bat

The world was in the middle of the most pressing public health risk his generation had ever seen, and JP Gabriel felt like he was sitting on the sidelines. As a VP of biologics and mRNA manufacturing at Ultragenyx, Gabriel watched from the sidelines as players like Pfizer/BioNTech and Moderna used mRNA tech to chase their own Covid-19 vaccines.

This month, Gabriel got the chance to get his hands dirty against the pandemic — but it won’t be with mRNA.

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Sen. Patty Murray (D-WA) (Graeme Sloan/Sipa USA/Sipa via AP Images)

Sen­a­tors to NIH: Do more to pro­tect US bio­med­ical re­search from for­eign in­flu­ence

Although Thursday’s Senate health committee hearing was focused on how foreign countries and adversaries might be trying to steal or negatively influence biomedical research in the US, the only country mentioned by the senators and expert witnesses was China.

Committee chair Patty Murray (D-WA) made clear in her opening remarks that the US cannot “let the few instances of bad actors” overshadow the hard work of the many immigrant researchers in the US, many of which have won Nobel prizes for their work. But she also said, “There is more the NIH can be doing here.”

Michel Vounatsos, Biogen CEO (Biogen via YouTube)

Damn the crit­ics, Bio­gen CEO Vounatsos or­ders full speed ahead on prep­ping a con­tro­ver­sial ad­u­canum­ab launch as FDA de­ci­sion looms

Right now one of the most interesting parlor games on Wall Street is offering odds on Biogen’s chances of getting an FDA OK on their controversial Alzheimer’s drug aducanumab.

For most objective players, it looks about like a coin toss, maybe a little worse than 50/50, as the Street balances the bull case of a full, mega blockbuster approval, a restricted approval or a disastrous order to go back to the clinic and mount a new Phase III. That last option was clearly the guidance most of the outside experts in the panel review offered the agency, as the industry is still puzzling out the question of whether or not the FDA is getting tougher in its oversight of drug development.

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