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?

The FDA on Tuesday released a warning letter sent earlier this month to the Mason, OH-based site of Procter & Gamble Manufactura, raising questions about the list of ingredients on the label and in the electronic filing.

The warning says that for P&G’s over-the-counter Vicks Nyquil Severe Hot Remedy Cold and Flu Plus Congestion, there’s a “mismatched” list of active ingredients between the labeling and the electronic listing file. The listing file for the active ingredients did not match the active ingredients in the electronic file.

The Federal Trade Commission has gotten involved in a patent feud over Supernus’ Parkinson’s drug Apokyn, a case the agency said may have ‘‘significant implications” for patients who rely on the drug.

Sage Chemical won the first generic approval for its Apokyn formulation (also known as apomorphine hydrochloride injection) back in 2022. The non-ergoline dopamine agonist is approved to treat Parkinson’s symptoms during “off episodes,” such as difficulty moving, tremors and intense cramping. However, regulators specified that the approval pertained to the generic drug cartridges only, not the injector pen required for administration.

The White House’s Office of Science and Technology Policy (OSTP) last year sought to find ways to better coordinate large-scale clinical trials in the US — as the UK lead by example during the pandemic — especially for these emergency clinical trials.

The lobbying group PhRMA Tuesday called for more clinical trial diversity in underserved areas, including by making participation less of a burden, and expanding eligibility criteria when appropriate.