UCB Presents Final Results from Phase II Study of Rozanolixizumab in Primary Immune Thrombocytopenia (ITP) at 2019 ASH Annual Meeting

Brussels (ots/PRNewswire) - UCB, a global biopharmaceutical company, today announced positive results from a Phase II study (TP0001; NCT02718716) of its novel, first-in-class subcutaneous (SC, under the skin) monoclonal antibody, rozanolixizumab, in patients with primary immune thrombocytopenia (ITP). The data were presented during an oral presentation today at the 61st American Society of Hematology (ASH) Annual Meeting & Exposition in Orlando, Florida.

- Phase II data demonstrate that rozanolixizumab was well tolerated by patients with primary ITP across all dose groups

- Clinically relevant improvements in platelet count and decrease in immunoglobin G (IgG) levels were observed in all dose groups

- Safety, tolerability and efficacy data support Phase III development of rozanolixizumab for primary ITP

- Rozanolixizumab's subcutaneous route of administration could provide a new treatment option for patients with primary ITP

The Phase II TP0001 study to assess the safety, tolerability and efficacy of rozanolixizumab was designed to explore a multiple dose regimen in order to inform the dosing strategy for further development in ITP. Sixty-six patients received either a single dose (1 x 15 mg/kg or 1 x 20 mg/kg) or multiple doses (5 x 4 mg/kg, 3 x 7 mg/kg, 2 x 10 mg/kg weekly) of SC rozanolixizumab. The total weekly dose was similar in all treatment groups, ranging from 15 to 21 mg/kg.

Clinically relevant improvements (i.e., reaching >=50x109/L) in platelet count and decreases in immunoglobin G (IgG) levels were observed across all dose groups, with higher response rate (55-67% in 1 x 15 mg/kg and 1 x 20 mg/kg dose groups vs 36-45% in 5 x 4 mg/kg, 3 x 7 mg/kg and 2 x 10 mg/kg dose groups) and shorter time to response achieved by the 1 x 15 mg/kg and 1 x 20 mg/kg rozanolixizumab dose groups.i

Results confirm that rozanolixizumab was well tolerated across all dose groups,[i]consistentwithpreviousrozanolixizumabstudies.[ii],[iii]Themostcommonlyreportedadverseeventwasheadache,withmild-to-moderateheadachesseenathigherdoses;otherreportedadverseeventsincludeddiarrheaandvomiting.Theseeventswereusuallyofshortdurationandthemajorityofeventsresolvedwithouttreatment.Nopatientdiscontinuedthestudyduetosideeffects.i

"ITPisasevere,oftenchronicdiseasethatcanhaveasignificant,long-termimpactonpeople'shealthandqualityoflife.Despiteapprovedtherapies,thereisstillanurgentneedfornewtreatmentoptionsthatarewelltoleratedandprovideasustainedincreaseinplateletcount,"saidProfessorTadeuszRobak,ProfessorofHematologyattheMedicalUniversityofLodz,Poland."ThesePhaseIIresultsforrozanolixizumabsuggestthetreatmentcouldreduceIgGautoantibodylevelsandimproveplateletcountforpeoplelivingwithprimaryITP."

IndividualslivingwithITPexperienceunpredictableanddebilitatingsymptomsincludingspontaneousbruising,bleedingandfatiguethatcangreatlyimpacttheiractivitiesofdailylife.[iv]Additionally,thelimitedcurrenttreatmentoptionsforpeoplewithITPcanbetime-consumingandinvasive.Thereisaneedtodiscovernewsolutionsthathavethepotentialtoimprovepatients'healthoutcomesandqualityoflife.RozanolixizumabisanadvancedSCanti-neonatalFcreceptor(FcRn)therapycurrentlyinclinicaldevelopmentandhasthepotentialtoprovideatargeted,convenientoptiontooptimizeindividualizedpatientcare.

"Ourresearchhasenabledustobetterunderstandrare,IgGautoantibody-mediateddiseasessuchasITP,includingwheregapsexistwithinthetreatmentparadigmandtheoverallpatientexperience,"saidDr.IrisLoew-Friedrich,ChiefMedicalOfficer,ExecutiveVice-President,UCB."TheseresultsreaffirmourbeliefthattargetingtheneonatalFcreceptorpathwaycouldhavethepotentialtotransformthetreatmentexperienceforpeoplewithITP.WelookforwardtoexpandingthisknowledgeinPhaseIIItrialsinITPandotherpatientpopulations."

Abouttherozanolixizumabclinicalstudyi

TP0001(NCT02718716)isaPhaseII,multi-center,open-label,multiple-dosestudyofrozanolixizumabinpatientswithprimaryITP.Sixty-sixpatientswereassignedtooneoffivegroupswithdifferentdosingregimens(5x4mg/kg,3x7mg/kg,2x10mg/kgweekly,1x15mg/kgor1x20mg/kg),receivingrozanolixizumabbySCinfusion(multipledoseswereadministeredatweeklyintervals).Allpatientsweremonitoredforan8-weekobservationperiodaftercompletionoftreatment.TheprimaryobjectiveofthestudyassessedsafetyandtolerabilityofrozanolixizumabadministeredbySCinfusion,andthesecondaryobjectiveconsideredtheclinicalefficacy(plateletcount)andpharmacodynamic(totalIgG)effects.ThestudywasdesignedtoexplorearangeoftherapeuticdosesinordertodevelopanappropriatedosingregimenforpatientswithITP.

Rozanolixizumabwaswelltoleratedacrossalldosegroups(4-20mg/kg)withmild-to-moderateheadachesseenathigherdoses;nopatientdiscontinuedthestudyduetosideeffects.

Inthestudy,clinicallyrelevantimprovementsinplateletcount(to>=50x109/L)wereobservedinpatientswithprimaryITPreceivingrozanolixizumabacrossalldosegroupsanddecreasesinserumIgGconcentrationwereobserved.Byday8,morepatientsreceivingasingle,higher-doseinfusionachievedplateletcountsof>=50x109/L(58.3%and54.5%inthe1x15mg/kgand1x20mg/kgdosegroups,respectively)comparedwithpatientsinthemultiple-dosecohorts(7.1%,14.3%and27.3%inthe5x4mg/kg,3x7mg/kg,and2x10mg/kggroups,respectively).Afastertimetoresponsewasalsoobservedinthe1x15and1x20mg/kgdosegroups(median7daysand5days,respectively),comparedwithpatientsinthemultiple-dosecohorts(14daysinboththe5x4mg/kgand3x7mg/kggroupsand8daysinthe2x10mg/kggroup)followingtreatment.

Aboutprimaryimmunethrombocytopenia

PrimaryITPisanacquiredautoimmunedisordercharacterized,inmostcases,bythepresenceofpathogenicIgGautoantibodies,withanestimatedprevalenceofapproximately10peopleper100,000(USA)[v].PathogenicIgGautoantibodiestargetplateletsandmegakaryocytes(plateletprecursors),leadingtotheremovalanddestructionofbothcirculatingandnewlyformedplatelets[vi],[vii],[viii]ultimatelyresultinginapropensityforbleedinginpatientswithITP.ThestandardofcareforpatientswithnewlydiagnosedITPconsistsofcorticosteroidsorintravenousimmunoglobulin(IVIg).[ix]PatientsintoleranttocorticosteroidsorwithcontraindicationsaretreatedwithIVIgoranti-D(whereappropriate),eitheraloneorincombination.Subsequenttreatmentsincludeimmunosuppressiveagents(e.g.,azathioprineandmycophenolatemofetil),rituximab,TPOreceptoragonists(e.g.,eltrombopagandromiplostim)orsplenectomy.[x]

Aboutrozanolixizumab

Rozanolixizumabisasubcutaneouslyadministered,humanizedmonoclonalantibodythatspecificallybinds,withhighaffinity,tohumanFcRn.IthasbeendesignedtoblocktheinteractionofFcRnandIgG,inhibitingIgGrecyclingandinducingtheremovalofpathogenicIgGautoantibodies.[ii],[xi]

RozanolixizumabisunderclinicaldevelopmentwiththeaimofimprovingthelivesofpeoplewithpathogenicIgG-autoantibody-drivenautoimmunediseases,includingITP,myastheniagravis(MG)andchronicinflammatorydemyelinatingpolyneuropathy(CIDP),bydrivingremovalofpathogenicIgGautoantibodies.

Rozanolixizumab,aninvestigationalmonoclonalantibody,wasgrantedorphandrugdesignationforthetreatmentofITPbytheUSFoodandDrugAdministrationon30April2018andbytheEuropeanCommissionon11January2019.[xii],[xiii]Thesafetyandefficacyofrozanolixizumabhasnotbeenestablished;itisnotcurrentlyapprovedbyanyregulatoryauthorityworldwide.

AboutUCB

UCB,Brussels,Belgium(www.ucb.com)isaglobalbiopharmaceuticalcompanyfocusedonthediscoveryanddevelopmentofinnovativemedicinesandsolutionstotransformthelivesofpeoplelivingwithseverediseasesoftheimmunesystemorofthecentralnervoussystem.With7,500peopleinapproximately40countries,thecompanygeneratedrevenueofEUR4.6billionin2018.UCBislistedonEuronextBrussels(symbol:UCB).FollowusonTwitter:@UCB_news

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References

[i] Robak, T., Kasmierczak, M., Jarque, I. et al. (2019). Rozanolixizumab, an anti-FcRn Antibody: Final results from a phase II, multiple-dose study in patients with primary immune thrombocytopenia. Blood. 134(1)

[ii] Kiessling, P., R. Lledo-Garcia, S. Watanabe et al. (2017) The FcRn inhibitor rozanolixizumab reduces human serum IgG concentration: A randomized phase 1 study. Sci Transl Med. 9(414)

[iii] Bril, V., M. Benatar, M. Brock et al. (2019) Proof-of-Concept and Safety of the Anti-FcRn Antibody Rozanolixizumab in Patients with Moderate-to-Severe Generalized Myasthenia Gravis (GMG): A Phase 2a Study. Neurology(Abstracts: AAN 71th Annual Meeting, Philadelphia):pS43.001

[iv] Kohli, R. and S. Chaturvedi (2019) Epidemiology and Clinical Manifestations of Immune Thrombocytopenia. Hamostaseologie(EFirst)

[v] National Organization for Rare Disorders (NORD). Immune thrombocytopenia. Retrieved from: https://rarediseases.org/rare-diseases/immune-thrombocytopenia/ Accessed December 2019

[vi] Cortelazzo, S., G. Finazzi, M. Buelli, A. Molteni, P. Viero, and T. Barbui (1991) High risk of severe bleeding in aged patients with chronic idiopathic thrombocytopenic purpura. Blood. 77(1):p31-3

[vii] Chang, M., P.A. Nakagawa, S.A. Williams et al. (2003) Immune thrombocytopenic purpura (ITP) plasma and purified ITP monoclonal autoantibodies inhibit megakaryocytopoiesis in vitro. Blood. 102(3):p887-95

[viii] Chan, H., J.C. Moore, C.N. Finch, T.E. Warkentin, and J.G. Kelton (2003) The IgG subclasses of platelet-associated autoantibodies directed against platelet glycoproteins IIb/IIIa in patients with idiopathic thrombocytopenic purpura. Br J Haematol. 122(5):p818-24

[ix] Neunert, C., W. Lim, M. Crowther et al. (2011) The American Society of Hematology 2011 evidence-based practice guideline for immune thrombocytopenia. Blood. 117(16):p4190-207

[x] Provan, D., R. Stasi, A.C. Newland et al. (2010) International consensus report on the investigation and management of primary immune thrombocytopenia. Blood. 115(2):p168-86

[xi] Smith B, Kiessling A, Lledo-Garcia R, et al. Generation and characterization of a high affinity anti-human FcRn antibody, rozanolixizumab, and the effects of different molecular formats on the reduction of plasma IgG concentration. MAbs2018;10:1111-30

[xii] U.S. Food and Drug Administration (FDA). (2018). Orphan drug designations and approvals. Retrieved from: https://www.accessdata.fda.gov/scripts/opdlisting/oopd/detailedIndex.cfm?cfgridkey=636618 Accessed December 2019

[xiii] European Medicines Agency (EMA). (2019). Public summary of opinion on orphan designation. Retrieved from: https://www.ema.europa.eu/en/medicines/human/orphan-designations/eu3182131 Accessed December 2019

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