“There hasn’t been a lot go­ing on in the pain space”

A startup ze­roes in on non­ad­dic­tive pain treat­ments “Physi­cians feel like they only have one bul­let in their tool­box”

Bloomberg Businessweek (Asia) - - CONTENTS - Cyn­thia Koons

A paint­ing of bright red chilies hangs in the boss’s of­fice at Cen­trex­ion Ther­a­peu­tics. A wreath of the spicy pep­pers sits on the desk of the com­pany’s chief sci­en­tist. Chilies in one form or an­other seem to be ev­ery­where at the com­pany’s Bal­ti­more head­quar­ters. Led by for­mer Pfizer Chief Ex­ec­u­tive Of­fi­cer Jef­frey Kindler, Cen­trex­ion is de­vel­op­ing a new gen­er­a­tion of non­ad­dic­tive painkiller­s, and hot pep­pers could play a role.

About 100 mil­lion Amer­i­cans suf­fer from chronic pain—more than those liv­ing with di­a­betes, heart dis­ease, and can­cer com­bined, ac­cord­ing to the In­sti­tute of Medicine. “Peo­ple for the last 100,000 years have been chew­ing or smear­ing or smok­ing or try­ing agents in their en­vi­ron­ment to re­lieve pain,” says Daniel Carr, pres­i­dent of the Amer­i­can Acad­emy of Pain Medicine.

Many peo­ple in pain turn to opi­oid­based drugs such as Oxy­Con­tin, which are a lead­ing cause of drug ad­dic­tion and over­dose deaths in the U.S. Nar­cotics, in­clud­ing heroin, were re­spon­si­ble for more than 28,000 deaths in 2014, ac­cord­ing to the Cen­ters for Dis­ease Con­trol and Pre­ven­tion, which fig­ures at least half in­volved a pre­scrip­tion drug. The re­sult­ing bur­den on the Amer­i­can econ­omy is $635 bil­lion a year in med­i­cal costs and lost pro­duc­tiv­ity, ac­cord­ing to the In­sti­tute of Medicine. “When we talk about chronic pain, like chronic low-back pain, physi­cians feel like they only have one bul­let in their tool­box that works for many, many pa­tients,” says Michael Oshin­sky, pro­gram di­rec­tor for pain and mi­graine at the Na­tional In­sti­tutes of Health, about opi­oids.

The pharma in­dus­try has strug­gled to come up with al­ter­na­tives. No fewer than 33 ex­per­i­men­tal medicines for chronic pain went into clin­i­cal tri­als from 2009 to 2015, and all failed, Oshin­sky says.

The prob­lem with nar­cotics is that in treat­ing pain they af­fect an area of the brain that reg­is­ters in­tense plea­sure. Cen­trex­ion’s drugs are de­signed to tar­get pain di­rectly, with­out trig­ger­ing the brain’s re­ward sys­tem. The com­pany is de­vel­op­ing an in­jectable drug to treat arthri­tis and foot pain that con­tains a syn­thetic ver­sion of cap­saicin, a substance in chili plants. It’s the fur­thest along of five drugs Cen­trex­ion has in de­vel­op­ment and could hit the mar­ket by 2020. “Truth­fully, there aren’t many, if any, really safe, ef­fec­tive chron­ic­pain treat­ments that have good du­ra­tion, good safety, and non­ad­dic­tive prop­er­ties,” Kindler says.

Other com­pa­nies work­ing on nono­pi­oid pain re­lief in­clude Hy­dra Bio­sciences of Cam­bridge, Mass., and

Heron Ther­a­peu­tics of Red­wood City, Calif., which are tar­get­ing di­a­betic and post­op­er­a­tive pain, re­spec­tively. Pfizer and Eli Lilly last year re­sumed lat­estage tri­als of a non-opi­oid medicine for arthritic pain, which they halted after the U.S. Food and Drug Ad­min­is­tra­tion raised con­cerns that the en­tire class of drugs might have side ef­fects on the ner­vous sys­tem.

Kindler has kept a rel­a­tively low pro­file since abruptly re­tir­ing from the top job at Pfizer in 2010, at the age of 55. At the time, he said he needed to “recharge” after a “pe­riod ex­tremely de­mand­ing on me per­son­ally.” His more than four years as the head of Amer­ica’s big­gest pharma com­pany were dif­fi­cult ones: Pfizer’s top-selling drug, Lip­i­tor, was on the eve of los­ing patent pro­tec­tion, while promis­ing treat­ments for choles­terol and Alzheimer’s failed in tri­als. In one of the higher-pro­file moves of his ten­ure, Kindler bought ri­val drug­maker Wyeth for $68 bil­lion in 2009.

Since mov­ing into the CEO suite at Cen­trex­ion in 2013, Kindler has taken up de­vel­op­ment of a top­i­cal li­do­caine gel for mus­cle pain and painful skin con­di­tions. The ben­e­fits of work­ing with in­gre­di­ents like li­do­caine, used in den­tal work, and cap­saicin, avail­able as an over-the-counter top­i­cal pain re­lief cream, is that their side ef­fects are well un­der­stood, says Ker­rie Brady, the com­pany’s chief busi­ness of­fi­cer.

Cen­trex­ion has also ac­quired three drugs from

Boehringer In­gel­heim that tar­get dif­fer­ent forms of chronic pain. One works on the same re­cep­tor that a cannabi­noid tar­gets but with­out the min­dal­ter­ing ef­fects that mar­i­juana-de­rived med­i­ca­tions some­times exhibit. “There hasn’t been a lot go­ing on in the pain space,” says Brady. “There really hasn’t been a lot of in­no­va­tion out there.”

The bot­tom line Some 33 ex­per­i­men­tal ther­a­pies for pain failed in tri­als from 2009 to 2015. Cen­trex­ion thinks it can beat the odds.

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