How the sur­gi­cal set­ting con­tributes to the opi­oid cri­sis

The num­ber of Amer­i­cans who be­come ad­dict­ed to opi­oids fol­low­ing surgery is an un­der-re­port­ed im­pli­ca­tion of a cri­sis sweep­ing the na­tion. How did we get to a point where up to 440,000 peo­ple be­come ad­dicts this way — every year?

Amer­i­cans have the high­est rate of opi­oid con­sump­tion in the world. The per­son­al and pub­lic health costs of the opi­oid cri­sis are at the fore­front of the news cy­cle while the short- and long-term ef­fects in­crease every day. Un­der­stand­ing how the sur­gi­cal set­ting is a main con­trib­u­tor to the epi­dem­ic and tak­ing a snap­shot of its costs can spring­board ways to im­prove health­care by tak­ing a pre­ven­ta­tive ap­proach.

The re­liance on opi­oids in the sur­gi­cal set­ting

Opi­oids have been used in surgery since the sec­ond half of the 20th cen­tu­ry, as doc­tors ad­min­is­tered them in­tra­venous­ly along­side anes­thet­ic gas­es in an at­tempt to bal­ance anes­thet­ic tech­niques and min­i­mize the sig­nif­i­cant dan­gers and side ef­fects caused by use of the gas­es alone. While this progress fos­tered sur­gi­cal dis­cov­ery and ad­vance­ment, lit­tle room was made for con­cern about the ad­dic­tive na­ture of these med­i­cines. Re­lat­ed re­search was scant; in 1980, a short let­ter-to-the-ed­i­tor in the New Eng­land Jour­nal of Med­i­cine was heav­i­ly — and un­crit­i­cal­ly — cit­ed as ev­i­dence that ad­dic­tion was rare with long-term opi­oid ther­a­py. At the same time, the avail­abil­i­ty and af­ford­abil­i­ty of new syn­thet­ic opi­oids, like oxy­codone and hy­drocodone, in­creased as pain was viewed as a neg­a­tive out­come.

Mil­lions of surg­eries per­formed, mil­lions of opi­oids pre­scribed

In the Unit­ed States each year, 50 mil­lion surg­eries are per­formed and the con­tin­u­ing over-re­liance on post­op­er­a­tive opi­oids fu­els the cri­sis by both ex­pos­ing opi­oid naïve pa­tients to the nar­cotics and by leav­ing hun­dreds of mil­lions of left­over pills hid­ing in our com­mu­ni­ty med­i­cine cab­i­nets. Many peo­ple are first ex­posed to opi­oids at the time of surgery, fur­ther high­light­ing the role post-sur­gi­cal care can play in the opi­oid epi­dem­ic.  Cur­rent stud­ies rou­tine­ly point to post­op­er­a­tive sur­gi­cal opi­oid use as a gate­way to overuse and ad­dic­tion. As many as 6.5% of pa­tients that take opi­oids to man­age pain af­ter surgery may be­come per­sis­tent opi­oid users, rep­re­sent­ing 2.6 mil­lion peo­ple – and hun­dreds of thou­sands of those will be­come ad­dict­ed.

In­creased costs to so­ci­ety & the health­care sys­tem 

Opi­oid-re­lat­ed ad­verse drug events (ORADEs) that re­sult from opi­oids giv­en af­ter surgery add sig­nif­i­cant bur­den to a health­care sys­tem al­ready be­set by un­due fi­nan­cial pres­sure from all sides — and it’s use­ful to get an ap­prox­i­mate ac­count­ing of just how much and where the costs are in­curred.

A re­cent study in­di­cat­ed that 10.6% of pa­tients un­der­go­ing hos­pi­tal-based sur­gi­cal and en­do­scop­ic pro­ce­dures ex­pe­ri­ences at least one ORADE. Fur­ther, ORADEs were as­so­ci­at­ed with an $8225 in­crease in cost and 1.6-day in­crease in length of stay for the in­dex hos­pi­tal­iza­tion. This high­lights an im­por­tant op­por­tu­ni­ty for hos­pi­tals to im­prove both pa­tient safe­ty and cost through in­ter­ven­tions to re­duce opi­oids in the sur­gi­cal set­ting.

Be­yond the hos­pi­tal, chron­ic opi­oid users al­so con­sume more over­all health­care re­sources — to the tune of $18,074 ex­tra com­pared to nonusers.  This ac­counts for in­creased health­care spend­ing up­wards of $47 bil­lion an­nu­al­ly. Wor­ry­ing­ly, these num­bers may rep­re­sent an un­der­es­ti­ma­tion as sur­gi­cal pro­ce­dures may con­tin­ue to fun­nel pa­tients in­to ad­dic­tion faster than peo­ple tran­si­tion away from ad­dic­tion. And the fact re­mains that 46 peo­ple die every day from over­dos­es in­volv­ing pre­scrip­tion opi­oids.

Pre­vent­ing post-sur­gi­cal opi­oid use re­quires a mul­ti­fac­eted ap­proach

To ad­dress the scourge of ad­dic­tion that can fol­low from this un­der-re­port­ed path­way, a mul­ti-pronged strat­e­gy emerges.

A big step is ed­u­cat­ing health­care providers on the role of post-sur­gi­cal opi­oids in per­pet­u­at­ing the epi­dem­ic and il­lus­trat­ing meth­ods that uti­lize non-opi­oid treat­ment op­tions as the foun­da­tion of post­op­er­a­tive acute pain man­age­ment are key as they can pre­vent un­nec­es­sary ex­po­sure to opi­oids. There’s al­so the mat­ter of pa­tients ex­pect­ing ze­ro pain af­ter surgery. In­deed, many pa­tients ex­pect to have “pain-free” surgery. Pain is a nor­mal part of heal­ing and pa­tients should be giv­en re­al­is­tic ex­pec­ta­tions in or­der to pre­pare for the qual­i­ty, quan­ti­ty, lo­ca­tion, and du­ra­tion of pain that they will ex­pe­ri­ence. Teach­ing sur­geons and health­care providers new ways to re­boot the ex­pec­ta­tions of pa­tients with re­spect to post-sur­gi­cal pain is nec­es­sary — while al­so em­pha­siz­ing non-opi­oid treat­ment foun­da­tion to acute post­op­er­a­tive pain man­age­ment as a ma­jor step­ping stone in pre­ven­tion.

By putting an em­pha­sis on re­ly­ing on non-opi­oid treat­ment for acute post­op­er­a­tive pain man­age­ment and health­care provider ed­u­ca­tion strat­e­gy, we may be­gin to see sig­nif­i­cant re­duc­tions in health­care costs on top of po­ten­tial­ly curb­ing the opi­oid ad­dic­tions al­ready crip­pling so­ci­ety. Ad­di­tion­al­ly, non-opi­oid post­op­er­a­tive pain man­age­ment can re­sult in bet­ter pa­tient care and out­comes, pro­vid­ing ad­e­quate treat­ment with­out ex­pos­ing pa­tients to the risks as­so­ci­at­ed with opi­oids.

For more in­for­ma­tion click here.

Nick Leschly via Getty

UP­DAT­ED: Blue­bird shares sink as an­a­lysts puz­zle out $1.8M stick­er shock and an un­ex­pect­ed de­lay

Blue­bird bio $BLUE has un­veiled its price for the new­ly ap­proved gene ther­a­py Zyn­te­glo (Lenti­Glo­bin), which came as a big sur­prise. And it wasn’t the on­ly un­ex­pect­ed twist in to­day’s sto­ry.

With some an­a­lysts bet­ting on a $900,000 price for the β-tha­lassemia treat­ment in Eu­rope, where reg­u­la­tors pro­vid­ed a con­di­tion­al ear­ly OK, blue­bird CEO Nick Leschly said Fri­day morn­ing that the pa­tients who are suc­cess­ful­ly treat­ed with their drug over 5 years will be charged twice that — $1.8 mil­lion — on the con­ti­nent. That makes this drug the sec­ond most ex­pen­sive ther­a­py on the plan­et, just be­hind No­var­tis’ new­ly ap­proved Zol­gens­ma at $2.1 mil­lion, with an­a­lysts still wait­ing to see what kind of pre­mi­um can be had in the US.


Glob­al Blood Ther­a­peu­tics poised to sub­mit ap­pli­ca­tion for ac­cel­er­at­ed ap­proval, with new piv­otal da­ta on its sick­le cell dis­ease drug

Global Blood Therapeutics is set to submit an application for accelerated approval in the second-half of this year, after unveiling fresh data from a late-stage trial that showed just over half the patients given the highest dose of its experimental sickle cell disease drug experienced a statistically significant improvement in oxygen-wielding hemoglobin, meeting the study's main goal.

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Gene ther­a­pies seize the top of the list of the most ex­pen­sive drugs on the plan­et — and that trend has just be­gun

Anyone looking for a few simple reasons why the gene therapy field has caught fire with the pharma giants need only look at the new list of the 10 most expensive therapies from GoodRx.

Two recently approved gene therapies sit atop this list, with Novartis’ Zolgensma crowned the king of the priciest drugs at $2.1 million. Right below is Luxturna, the $850,000 pioneer from Spark, which Roche is pushing hard to acquire as it adds a gene therapy group to the global mix.

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Bain’s biotech team has cre­at­ed a $1B-plus fund — with an eye to more Big Phar­ma spin­outs

One of the biggest investors to burst onto the biotech scene in recent years has re-upped with more than a billion dollars flowing into its second fund. And this next wave of bets will likely include more of the Big Pharma spinouts that highlighted their first 3 years in action.

Adam Koppel and Jeff Schwartz got the new life sciences fund at Bain Capital into gear in the spring of 2016, as they were putting together a $720 million fund with $600 million flowing in from external investors and the rest drawn from the Bain side of the equation. This time the external investors chipped in $900 million, with Bain coming in for roughly $180 million more.

They’re not done with Fund I, with plans to add a couple more deals to the 15 they’ve already posted. And once again, they’re estimating another 15 to 20 investments over a 3- to 5-year time horizon for Fund II.

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News­mak­ers at #EHA19: Re­gen­eron, Ar­Qule track progress on re­sponse rates

Re­gen­eron’s close­ly-watched bis­pe­cif­ic con­tin­ues to ring up high re­sponse rates

Re­gen­eron’s high-pro­file bis­pe­cif­ic REGN1979 is back in the spot­light at the Eu­ro­pean Hema­tol­ogy As­so­ci­a­tion sci­en­tif­ic con­fab. And while the stel­lar num­bers we saw at ASH have erod­ed some­what as more blood can­cer pa­tients are eval­u­at­ed, the re­sponse rates for this CD3/CD20 drug re­main high.

A to­tal of 13 out of 14 fol­lic­u­lar lym­phomas re­spond­ed to the drug, a 93% ORR, down from 100% at the last read­out. In 10 out of 14, there was a com­plete re­sponse. In dif­fuse large B-cell lym­phoma the re­sponse rate was 57% among pa­tients treat­ed at the 80 mg to 160 mg dose range. They were all com­plete re­spons­es. And 2 of these Cars were for pa­tients who had failed CAR-T ther­a­py.

Neil Woodford, Woodford Investment Management via YouTube

Un­der siege, in­vest­ment man­ag­er Wood­ford faces an­oth­er in­vest­ment shock

Em­bat­tled UK fund man­ag­er Neil Wood­ford — who has con­tro­ver­sial­ly blocked in­vestors from pulling out from his flag­ship fund to stem the blood­let­ting, af­ter a slew of dis­ap­point­ed in­vestors fled fol­low­ing a se­ries of sour bets — is now pay­ing the price for his ac­tions via an in­vestor ex­o­dus on an­oth­er fund.

Har­g­reaves Lans­down, which has in the past sold and pro­mot­ed the Wood­ford funds via its re­tail in­vest­ment plat­form, has re­port­ed­ly with­drawn £45 mil­lion — its en­tire po­si­tion — from the in­vest­ment man­ag­er’s In­come Fo­cus Fund.

Search­ing for the next block­buster to fol­low Darza­lex, J&J finds a $150M an­ti-CD38 drug from part­ner Gen­mab

Now that J&J and Genmab have thrust Darzalex onto the regulatory orbit for first-line use in multiple myeloma, the partners are lining up a deal for a next-gen follow-on to the leading CD38 drug.

Janssen — J&J’s biotech unit — has its eyes on HexaBody-CD38, a preclinical compound generated on Genmab’s tech platform designed to make drugs more potent via hexamerization.

Genmab is footing the bill on studies in multiple myeloma and diffuse large B-cell lymphoma; once it completes clinical proof of concept, Janssen has the option to license the drug for a $150 million exercise fee. There’s also $125 million worth of milestones in play.

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Ab­b­Vie touts new da­ta for Hu­mi­ra suc­ces­sor; Gilead inks dis­cov­ery deal

→ Ab­b­Vie is tout­ing new pos­i­tive da­ta com­par­ing their ag­ing block­buster Hu­mi­ra with their hoped-for block­buster upadac­i­tinib. Over 48 weeks a larg­er pro­por­tion of pa­tients tak­ing the ex­per­i­men­tal drug ex­pe­ri­enced clin­i­cal re­mis­sion than in the con­trol arm with Hu­mi­ra. Their drug brought in $20 bil­lion last year, top­ping the scales in the num­ber 1 slot.

→ Gilead has turned to Van­cou­ver-based Ab­Cellera for its lat­est dis­cov­ery deal. Ab­Cellera will use its know-how in “sin­gle-cell screen­ing of nat­ur­al im­mune sources” to find an­ti­body can­di­dates for Gilead to pur­sue in the in­fec­tious dis­ease field. The deal in­cludes an up­front and mile­stones.

Turns out, Rudy Tanzi did­n't see much of a sto­ry about a hid­den link be­tween En­brel and Alzheimer's ei­ther

The Wash­ing­ton Post man­aged to whip up the quick­est in­dus­try con­sen­sus I’ve ever seen that one of its re­porters was pur­vey­ing overblown non­sense with a sto­ry that Pfiz­er was sit­ting on da­ta sug­gest­ing that En­brel could be an ef­fec­tive treat­ment for Alzheimer’s. 

In cov­er­ing that bit of an­ti-Big Phar­ma fan­ta­sy — there are lots of rea­sons to go af­ter phar­ma, but this piece was lu­di­crous — I not­ed com­ments in the sto­ry from some promi­nent peo­ple in the field crit­i­ciz­ing Pfiz­er for not pub­lish­ing the da­ta. I sin­gled out Rudy Tanzi at Har­vard and then ap­plied some added crit­i­cism for the things he’s done to hype — in my opin­ion — high­ly ques­tion­able as­sump­tions. You can see it in the link.