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?

UP­DAT­ED: FDA’s golodirsen CRL: Sarep­ta’s Duchenne drugs are dan­ger­ous to pa­tients, of­fer­ing on­ly a small ben­e­fit. And where's that con­fir­ma­to­ry tri­al?

Back last summer, Sarepta CEO Doug Ingram told Duchenne MD families and investors that the FDA’s shock rejection of their second Duchenne MD drug golodirsen was due to some concerns regulators raised about the risk of infection and the possibility of kidney toxicity. But when pressed to release the letter for all to see, he declined, according to a report from BioPharmaDive, saying that kind of move “might not look like we’re being as respectful as we’d like to be.”

He went on to assure everyone that he hadn’t misrepresented the CRL.

But Ingram’s public remarks didn’t include everything in the letter, which — following the FDA’s surprise about-face and unexplained approval — has now been posted on the FDA’s website and broadly circulated on Twitter early Wednesday.

The CRL raises plenty of fresh questions about why the FDA abruptly decided to reverse itself and hand out an OK for a drug a senior regulator at the FDA believed — 5 months ago, when he wrote the letter — is dangerous to patients. It also puts the spotlight back on Sarepta $SRPT, which failed to launch a confirmatory study of eteplirsen, which was only approved after a heated internal controversy at the FDA. Ellis Unger, director of CDER’s Office of Drug Evaluation I, notes that study could have clarified quite a lot about the benefit and risks associated with their drugs — which can cost as much as a million dollars per patient per year, depending on weight.

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2019 Trin­i­ty Drug In­dex Eval­u­ates Ac­tu­al Com­mer­cial Per­for­mance of Nov­el Drugs Ap­proved in 2016

Fewer Approvals, but Neurology Rivals Oncology and Sees Major Innovations

This report, the fourth in our Trinity Drug Index series, outlines key themes and emerging trends in the industry as we progress towards a new world of targeted and innovative products. It provides a comprehensive evaluation of the performance of novel drugs approved by the FDA in 2016, scoring each on its commercial performance, therapeutic value, and R&D investment (Table 1: Drug ranking – Ratings on a 1-5 scale).

How to cap­i­talise on a lean launch

For start-up biotechnology companies and resource stretched pharmaceutical organisations, launching a novel product can be challenging. Lean teams can make setting a launch strategy and achieving your commercial goals seem like a colossal undertaking, but can these barriers be transformed into opportunities that work to your brand’s advantage?
We spoke to Managing Consultant Frances Hendry to find out how Blue Latitude Health partnered with a fledgling subsidiary of a pharmaceutical organisation to launch an innovative product in a
complex market.
What does the launch environment look like for this product?
FH: We started working on the product at Phase II and now we’re going into Phase III trials. There is a significant unmet need in this disease area, and everyone is excited about the launch. However, the organisation is still evolving and the team is quite small – naturally this causes a little turbulence.

Stephen Hahn, AP

The FDA has de­val­ued the gold stan­dard on R&D. And that threat­ens every­one in drug de­vel­op­ment

Bioregnum Opinion Column by John Carroll

A few weeks ago, when Stephen Hahn was being lightly queried by Senators in his confirmation hearing as the new commissioner of the FDA, he made the usual vow to maintain the gold standard in drug development.

Neatly summarized, that standard requires the agency to sign off on clinical data — usually from two, well-controlled human studies — that prove a drug’s benefit outweighs any risks.

Over the last few years, biopharma has enjoyed an unprecedented loosening over just what it takes to clear that bar. Regulators are more willing to drop the second trial requirement ahead of an accelerated approval — particularly if they have an unmet medical need where patients are clamoring for a therapy.

That confirmatory trial the FDA demands can wait a few years. And most everyone in biopharma would tell you that’s the right thing for patients. They know its a tonic for everyone in the industry faced with pushing a drug through clinical development. And it’s helped inspire a global biotech boom.

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Eli Lil­ly’s $1.6B can­cer drug failed to spark even the slight­est pos­i­tive gain for pa­tients in its 1st PhI­II

Eli Lilly had high hopes for its pegylated IL-10 drug pegilodecakin when it bought Armo last year for $1.6 billion in cash. But after reporting a few months ago that it had failed a Phase III in pancreatic cancer, without the data, its likely value has plunged. And now we’re getting some exact data that underscore just how little positive effect it had.

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Am­gen aug­ments Asia foothold by tak­ing over Astel­las joint ven­ture in Japan

California-based Amgen, which does the bulk of its business in the United States, made its ambition to reinvigorate its growth prospects by expanding its presence in Asia clear at the sidelines of the JP Morgan healthcare conference in San Francisco earlier this month.

The Thousand Oaks-based company on Thursday executed its plan to dissolve the joint venture with Astellas — created in 2013 — to operate the unit independently in Japan. With its rapidly aging population, the region represents an appealing market for Amgen’s osteoporosis treatments Prolia and Evenity as well as a cholesterol-lowering injection Repatha.

Daphne Zohar (PureTech)

PureTech bags $200M from sale of Karuna shares — still siz­zling from promis­ing schiz­o­phre­nia da­ta

Cashing in on the exuberance around Karuna Therapeutics and its potential blockbuster CNS drug, PureTech has sold a chunk of the biotech’s shares to Goldman Sachs for $200 million.

Boston-based PureTech had helped Eli Lilly vet Steve Paul launch Karuna and invent its lead program, which combines two old drugs that both act on the muscarinic receptor and balances each other out. Xanomeline, a discard from Lilly, stimulates the M1 and M4 receptors; trospium is an muscarinic receptor antagonist approved to treat overactive bladders.

UP­DAT­ED: New play­ers are jump­ing in­to the scram­ble to de­vel­op a vac­cine as pan­dem­ic pan­ic spreads fast

When the CNN news crew in Wuhan caught wind of the Chinese government’s plan to quarantine the city of 11 million people, they made a run for one of the last trains out — their Atlanta colleagues urging them on. On the way to the train station, they were forced to skirt the local seafood market, where the coronavirus at the heart of a brewing outbreak may have taken root.

And they breathlessly reported every moment of the early morning dash.

In shuttering the city, triggering an exodus of masked residents who caught wind of the quarantine ahead of time, China signaled that they were prepared to take extreme actions to stop the spread of a virus that has claimed 17 lives, sickened many more and panicked people around the globe.

CNN helped illustrate how hard all that can be.

The early reaction in the biotech industry has been classic, with small-cap companies scrambling to headline efforts to step in fast. But there are also new players in the field with new tech that has been introduced since the last of a series of pandemic panics that could change the usual storylines. And they’re volunteering for a crash course in speeding up vaccine development — a field where overnight solutions have been impossible to prove.

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Roche cracks Chi­na's ADC mar­ket open as Kad­cy­la scores its first breast can­cer OK in the coun­try

Roche’s Kadcyla has become the first antibody-drug conjugate to enter the Chinese market, marking a dramatic advance for both the Swiss pharma giant and the therapeutic class.

The local arm of Roche announced the approval late Tuesday, which covers the therapy’s use in the adjuvant setting in patients with early HER-2 positive breast cancer who still have residual invasive disease after receiving paclitaxel and Herceptin as neoadjuvant treatment.