profile symptoms andcraving. Taken together, nonopioidillicitdruguse. reduce illicitopioidusewith nocompensatory theseproperties effects ofillicitopioidsandhelping to control inthe brainof70%to 80%over withdrawal drug-liking thesubjective theentireoccupancy 1-month period, blocking inthe treatment shift ofopioid usedisorder.medications andis an evidence-based have Clinicaltrials suggested thatthistreatment receptor results in aμ-opioid Fig. 1|Four generations ofbuprenorphine treatments to fight opioid usedisorder. B8 nearly 50,000 deaths attributed to 50,000deathsattributed drugoverdose.nearly more to dollarsandcontributes thanhalfatrillion theUnited States alone,In opioidusedisorder costs Overcoming disorder use opioid recovery.” patientsontheirpathway topeutics thatsupport dedicated to thedevelopment ofinnovative thera- “Indivior’s R&D[research and development] is solutions,” said Indivior’s Heidbreder. CSO Christian nature ofrelapse requires scientific pioneering disorders ofaddiction. tion andthechronic conditions andco-occurring understandingofaddic- through its industry-leading tive medicationsthathelptransform patients’ lives pany withamissionto discover anddevelop innova- high rates ofnonadherence andrelapse. treatment, to illnessesthatcontribute orcomorbid to social stigma, lack of awareness of or access to needowing donotgetthehelp they with addiction ofmedications,ability many individuals who struggle has reached Despite theavail- epidemicproportions. Substance usedisorder that isaglobalhealthcrisis tional state whenaccessto thedrugiswithdrawn. ing intake, and the emergence of anegative emo- the drug,seek and take the loss of control in limit- tive processes regulatory leads to the compulsion to intheneural circuits that control cogni-Dysfunction bycharacterized long-lastingchangesinthebrain. isachronically relapsingDrug addiction disorder opioids, alcohol, andstimulants, aswell as accompanying illnesses such as schizophrenia. Taking a patient-centered approach, Indivior is developing innovative treatments to for addiction struggle against substance use disorder Fighting apathy and lack of awareness in the www.indivior.com Inc. Indivior Indivior is a global specialty pharmaceutical com- pharmaceutical isaglobalspecialty Indivior “The inherentandmultidimensional complexity “The |November 2018 | biopharmadealmakers.nature.com no compensatory non-opioid illicitdruguse( non-opioid no compensatory together, reduce illicitopioidusewith theseproperties to control withdrawal symptoms andcraving. Taken effects ofillicitopioidsandhelping tive drug-liking thesubjec- period, blocking the entire one-month receptor of 70% toμ-opioid 80% over occupancy have suggested thatthistreatment results inbrain in thetreatment ofopioidusedisorder. Clinicaltrials formulation (SUBLOCADE) ( buprenorphine injectable approved once-monthly the firstUSFood andDrugAdministration (FDA)- and naloxone sublingualfilm(SUBOXONE film),and sublingual tablets (SUBOXONE), buprenorphine tablets (SUBUTEX),buprenorphine andnaloxone and include buprenorphine countries sublingual pany’s medicationsare available inmore than40 treatment ofopioiddependencein1996. The com- medicationfor thethe firstbuprenorphine-based receptor antagonist. GroupThe launched Indivior agonistandκ-opioid receptor partial a μ-opioid andsupplyofbuprenorphine,the manufacture ofcare ofcontinuity and through the importance tion treatment through community educationon with adherent patients. relapse costs compared and higher total health-care cations has been associated with increased odds of ment, thehighrate ofnonadherence to dailymedi- received treatment. Even for thosereceiving treat- use disorder, ofpatientshave ever onlyaminority ofmedicationstoDespite theavailability treat opioid SUBLOCADE shift represents anevidence-based Indivior has a long history of supporting the addic- of supporting has a long history Indivior Fig. 1 SUBLOCADE represents generationofbuprenorphine-based thefourth ). Fig. 2 ). ADVERTISER RETAINS FOR CONTENTADVERTISER SOLERESPONSIBILITY understand how to address the unmet needs of only thefirststep ofalongcommitmentto better adaptive changes in several neurotransmitter sys- in patientsinitiatingtreatment withSUBLOCADE,” to ofrecovery understandthetrue determinants involves theimplementationofreal-world studies and potentially changestandards ofcare. environment to prevent repeated opioidoverdoses the effects ofSUBLOCADE room intheemergency and Virginia Tech to Research Carilion study Institute Commonwealth University, Fairfax Inova Hospital with recently establishedapartnership Virginia patients suffering from opioidusedisorder. Indivior abuse andmay to alsocontribute thenegative positive reinforcing of several drugs properties of dopaminergic system, whichplays arole inthe tion ofGABA to psychostimulants depresses func- thenormal tems, includingGABAreceptor signaling. Exposure dopamine (DA) D B(GABA acid type γ-aminobutyric is developing innovative approaches thattarget alcohol andstimulants. To thatend, thecompany address to the unmet needs of patients addicted use disorder, therapies to is pioneering Indivior Beyond thedevelopment oftreatments for opioid approach All-encompassing Heidbreder said. “Another exampleof ourfocus onpatientsalso The FDA approval ofSUBLOCADE lastyear was Long-term exposure to drugsofabusecauses B receptor signaling in the mesolimbic 3 receptors. ADVERTISEMENT FEATUREADVERTISEMENT B ), orexin-1, and of Excellence inHull, andhas United Kingdom, elements of the mesolimbic DA system, together for alcoholandstimulantusedisorders. is Indivior target for thedevelopment ofpharmacotherapies density localization of the DAdensity D in response to drugsofabuse. The restricted high- mesolimbic DA system asacommondenominator OX1a selective receptor antagonist. to develop theirleadmolecule,Discovery C4X3256, withC4X hasenteredIndivior into apartnership abstinenceinanimalmodelsofaddiction. during relapse behavior orreinstatement ofdrug-seeking OX1 receptor andprevents decreases drugseeking ofthehomeostasis, whereas blockade selective andenergy in theregulation cycle ofthesleep/wake theOX2 receptordifferential isinvolved functionality: have ofexpression patterns inthebrainand distinct identified orexin receptors (OX1 and OX2) seem to substance usedisorders istheorexin receptor. Two pathway for asapriority thetreatmentby Indivior of able for treatment long-term withouttolerance. andto besuit toexpected offer selectivity superior physiologically. As aresult, thisleadcompoundis of GABA activity lead moleculeADX71441, whichonlyenhancesthe is also pursuing anotherIndivior strategy with their use disorder. withAddex partnership In Therapeutics, baclofen enantiomers, for thetreatment ofalcohol prodrug of( developing arbaclofen placarbil, anovel transported GABA reinforcing effects associated withtheirwithdrawal. phrenia or first-episode psychosisphrenia was42%. orfirst-episode patientsdiagnosedtreatment-seeking with schizo that theprevalence ofany substanceusedisorder in recent systematic review and meta-analysis revealed disorder,sonality andschizophrenia. For example, a order, disorder, borderline personality antisocialper bipolar disorder, dis hyperactivity attention-deficit disorders,psychiatric including anxiety, depression, substance use disorders are with highly comorbid Epidemiological and clinical studies have shown that Addressing associated illnesses medicine,” Heidbreder said. significant to addiction contributions tion andmake research centers to advancethescienceofaddic capital investment inR&D, we willleverage these new with substanceusedisorders. “As Indivior’s largest to pioneernovel treatments for patientsstruggling expanded itsR&DfacilitiesinFort Collins, Colorado, withAptuit. inpartnership APV202701A, developing a selective DA D behavior,drug-taking orstress. iscurrently Indivior cues that have been previously associated with sure to thedrugitself, to environmental re-exposure behavior triggered eitherby re-expo of drug-seeking drug’s rewarding efficacy, andreduce reinstatement drug-induced incentive motivation,attenuate the DAing that selective D ofnonclinicalstudies demonstrat by aseries ported for substanceusedisorder. This hypothesis issup receptor may translate into treatment anew option abuse, suggested targeting thatselectively theDA D D ofchangesintheexpressionwith evidence oftheDA ADVERTISER RETAINS FOR CONTENTADVERTISER SOLERESPONSIBILITY ADVERTISEMENT FEATUREADVERTISEMENT 3 In addition, Indivior has built a new R&DCenter hasbuiltanew addition,Indivior In Research has also pointed toward of the activation A secondmoleculartarget that has beenidentified receptor following repeated exposure to drugsof B agonists such as baclofen have been the R )-baclofen, themore ofthetwo active B receptors when and where needed 3 receptor antagonists reduce 3 receptor antagonist, 3 receptor into key ------3

doses of300 SUBLOCADE 300 which corresponded to 75%μORO. SUBLOCADE 300/300 and long-term, providing evidence-based training to providingand long-term, evidence-based patientprogressmonitoring medium, intheshort, ofcare,“Focusing ofcontinuity ontheimportance disorders andtheirtreatment,” Heidbreder said. andmisconceptionsaboutsubstanceuse barriers communities andwillprogressivelybreak down ment programs engagepatientsandtheir actively drugscreening.employment, andurine utilization,crime, housing,cal health,health-care family relationships, oflife, quality mentalandphysi encompass demographics, druguse, drugtreatment, fering from opioidusedisorder. The datacollected up to 24-monthlongitudinal datafrom patientssuf as the RECOVERknown Study), which is collecting Factorsand Socioeconomic (also onRecovery from Chronic OpioidUse:StudyingEnvironmental ment plans. ofitsclinicaldevelop outcome measures aspart into theintegrationand effort ofpatient-reported hasinvestedIndivior asubstantialamountoftime symptoms, oflife. theirmedication,andquality patients’ to withrespect their personalexperiences istheelucidationofprocess. Equally important to approval drug development and the regulatory remains pharmacotherapies safety essential ofnew and Thoroughly theclinicalefficacy characterizing Patient-focused culture Heidbreder said. address any may mentalillnessesthey suffer from,” use disorders from amore and holisticperspective for usto lookatpatientswithsubstance important issometimesdifficultto establish,itis comorbidity of schizophrenia inadults. forthe antipsychotic drugrisperidone thetreatment only once-monthly, form injectable of long-acting recently received FDA approval for PERSERIS,the improvements inmedication compliance. Indivior to 90%μORO. SUBLOCADE 300/100 increased withintherangeof70%to 90%μORO. The probabilityofzero craving alsoincreased 70% between wasfoundμORO to be2 effects ofafullopioidagonistsuchashydromorphone effectively drug-liking with70% blockthesubjective receptorμ-opioid (μORO). occupancy Fig. “Although ofthe ordirectionality thecausality antipsychoticsLong-acting may injectable facilitate “We believe that theseintegrated“We clinicaldevelop For haslaunchedtheRemission example, Indivior

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avg mg datasuggested that repeated monthlydosesof nature.com/biopharmadealmakers | November 2018| “Through agrassroots we’ve effort, “Through established Through closecollaborationwithregulators, contact of6.32 Email: [email protected] Tel: +1-804-594-4456 VA, USA Richmond, Indivior Inc. CSO Heidbreder, Christian

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