cerlipnase alfa (Brineura ) Applies t all prducts administered r underwritten by Blue Crss and Blue Shield f Luisiana and its subsidiary, HMO Luisiana, Inc.(cllectively referred t as the Cmpany ), unless therwise prvided in the applicable cntract. Medical technlgy is cnstantly evlving, and we reserve the right t review and update Medical Plicy peridically. When Services May Be Eligible fr Cverage Cverage fr eligible medical treatments r prcedures, drugs, devices r bilgical prducts may be prvided nly if: Benefits are available in the member s cntract/certificate, and Medical necessity criteria and guidelines are met. Based n review f available data, the Cmpany may cnsider cerlipnase alfa (Brineura ) t slw the lss f ambulatin in symptmatic pediatric patients with late infantile neurnal cerid lipfuscinsis type 2 (CLN2), als knwn as tripeptidyl peptidase 1 (TPP1) deficiency, t be eligible fr cverage. Patient Selectin Criteria Cverage eligibility fr cerlipnase alfa (Brineura) will be cnsidered when the fllwing criteria are met: Initial (6 mnths): Patient has a diagnsis f late infantile neurnal CLN2 [als knwn as TPP1 deficiency] as cnfirmed by ne f the fllwing diagnstic testing results: Deficient TPP1 activity in leukcytyes; OR Pathgenic variants/mutatins in each allele f the TPP1/CLN2 gene (includes single gene sequencing, gene panels, r whle exme sequencing); AND Patient is 3 years f age r lder; AND Patient has a scre f AT LEAST 3 n the CLN2 Clinical Rating Scale (with AT LEAST a 1 in each f the Mtr and Language Dmains); AND Patient is symptmatic (e.g., seizures, lss f language, mtr abilities, delay f language develpment, unsteady gait, visual failure, etc.); AND Underlying neurlgical disrders that may have caused the patient s seizures r cgnitive decline have been ruled ut; AND Patient des NOT have a cntraindicatin fr neursurgery (e.g., cngenital heart disease r severe respiratry impairment); AND Patient des NOT have an underlying cnditin that wuld make the patient prne t cmplicatins frm using an intraventricular shunt (e.g., hydrcephalus r ventricular shunts); AND Patient has NOT had generalized mtr status epilepticus r severe infectins within 4 weeks befre the first scheduled dse f Brineura; AND Page 1 f 5
Brineura is dsed at 300 mg given every ther week as an intraventricular infusin fllwed by infusin f intraventricular electrlytes. Cntinuatin (1 year) Initial criteria were met; AND Patient is respnding t Brineura therapy: e.g., Patient DOES NOT have an unreversed 2 pint (r greater) decline frm baseline in the Mtr Dmain f the CLN2 Clinical Rating Scale OR patient DOES NOT have a scre f 0 in the Mtr Dmain f the CLN2 Clinical Rating Scale. Nte that the CLN2 Clinical Rating Scale is lcated in the Backgrund sectin f this plicy. The baseline CLN2 Clinical Rating Scale Scre (brken dwn by dmain) MUST be prvided when requesting the drug. When Services Are Cnsidered Nt Medically Necessary Based n review f available data, the Cmpany cnsiders the use f cerlipnase alfa (Brineura) when any f the fllwing patient selectin criteria are nt met t be nt medically necessary**: Fr Initial: Patient has a scre f AT LEAST 3 n the CLN2 Clinical Rating Scale (with AT LEAST a 1 in each f the Mtr and Language Dmains). Underlying neurlgical disrders that may have caused the patient s seizures r cgnitive decline have been ruled ut. Patient has NOT had generalized mtr status epilepticus r severe infectins within 4 weeks befre the first scheduled dse f Brineura. Fr Cntinuatin: Patient is respnding t Brineura therapy: e.g., Patient DOES NOT have an unreversed 2 pint (r greater) decline frm baseline in the Mtr Dmain f the CLN2 Clinical Rating Scale OR patient DOES NOT have a scre f 0 in the Mtr Dmain f the CLN2 Clinical Rating Scale. When Services Are Cnsidered Investigatinal Cverage is nt available fr investigatinal medical treatments r prcedures, drugs, devices r bilgical prducts. Based n review f available data, the Cmpany cnsiders the use f cerlipnase alfa (Brineura) when patient selectin criteria are nt met (with the exceptin f thse dented as nt medically necessary**) t be investigatinal.* Backgrund/Overview Brineura is a hydrlytic lyssmal N-terminal tripeptidyl peptidase indicated t slw the lss f ambulatin in symptmatic pediatric patients 3 years f age and lder with late infantile CLN2, als knwn as TPP1 deficiency. Deficiency in TPP1 activity results in the accumulatin f lyssmal strage materials nrmally Page 2 f 5
metablized by this enzyme in the central nervus system (CNS), leading t prgressive decline in mtr functin. Brineura, r cerlipnase alfa (rhttp1), a prenzyme, is taken up by target cells in the CNS and is translcated t the lyssmes thrugh the Catin Independent Mannse-6-Phsphate Receptr (CI-MPR, als knwn as M6P/IGF2 receptr). Brineura is activated in the lyssme and the activated prtelytic frm f rhtpp1 cleaves tripeptides frm the N-terminus f prteins. Brineura is essentially an enzyme replacement fr this cnditin. CLN2 is a rare cnditin (0.5 t 1 cases per 100,000 live births). As mentined earlier, this disease results in prgressive neurdegeneratin. The nset f CLN2 typically ccurs between 2 and 3 years f age. Lss f ambulatin is usually arund 6 years f age while prgressive visin lss and death ccur between 6 and 16 years f age. The rating scale used in clinical trials fr Brineura is listed belw: CLN2 Clinical Rating Scale: Dmain Scre CLN2 Scale Mtr 3 Grssly nrmal gait 2 Abnrmal gait, independent 10 steps, frequent falls, bvius clumsiness 1 N unaided walking r crawling nly; cannt walk 10 unassisted steps 0 Immbile, mstly bedridden Language 3 Grssly nrmal (age apprpriate) 2 Has becme recgnizably abnrmal (wrse than the individual maximum) 1 Hardly understandable 0 Unintelligible r n language FDA r Other Gvernmental Regulatry Apprval U.S. Fd and Drug Administratin (FDA) Brineura was apprved in 2017 t slw the lss f ambulatin in symptmatic pediatric patients 3 years f age and lder with late infantile CLN2, als knwn as TPP1 deficiency. Ratinale/Surce This medical plicy was develped thrugh cnsideratin f peer-reviewed medical literature generally recgnized by the relevant medical cmmunity, U.S. FDA apprval status, natinally accepted standards f medical practice and accepted standards f medical practice in this cmmunity, Blue Crss and Blue Shield Assciatin technlgy assessment prgram (TEC) and ther nn-affiliated technlgy evaluatin centers, reference t federal regulatins, ther plan medical plicies, and accredited natinal guidelines. The safety and efficacy f Brineura was assessed ver 96 weeks in a nn-randmized single-arm dse escalatin study with extensin in patients with late infantile CLN2 disease, as cnfirmed by TPP1 deficiency. The Brineura treated patients were cmpared t untreated patients frm a natural histry chrt. Page 3 f 5
Brineura treated patients had a Mtr-Language CLN2 Clinical Rating Scale scre f 3 prir t enrllment. Twenty-fur patients were enrlled. Patients were assessed fr decline in the Mtr Dmain f the CLN2 Clinical Rating Scale at 48, 72, and 96 weeks. Per the package insert, due t the inability t establish cmparability fr the CLN2 Language dmain ratings between the clinical study with extensin and the natural histry chrt, efficacy f Brineura fr the Language dmain cannt be established. In this study, f the 22 patients treated with Brineura, 95% were respnders (e.g., absence f a 2 pint decline in the Mtr Dmain f the CLN2 Clinical Rating Scale scre r absence f a scre f 0 in the Mtr Dmain f the CLN2 Clinical Rating Scale) at week 96 as cmpared t 50% in the natural histry chrt. References 1. Brineura [package insert]. Bimarin Pharmaceutical, Inc. Nvat, Califrnia. 2. Brineura Drug Evaluatin. Express Scripts. Updated June 2017. Plicy Histry 12/07/2017 Medical Plicy Cmmittee review 12/20/2017 Medical Plicy Implementatin Cmmittee apprval. New plicy. 02/06/2018 Cding update Next Scheduled Review Date: 12/2018 Cding The five character cdes included in the Blue Crss Blue Shield f Luisiana Medical Plicy Cverage Guidelines are btained frm Current Prcedural Terminlgy (CPT ), cpyright 2016 by the American Medical Assciatin (AMA). CPT is develped by the AMA as a listing f descriptive terms and five character identifying cdes and mdifiers fr reprting medical services and prcedures perfrmed by physician. The respnsibility fr the cntent f Blue Crss Blue Shield f Luisiana Medical Plicy Cverage Guidelines is with Blue Crss and Blue Shield f Luisiana and n endrsement by the AMA is intended r shuld be implied. The AMA disclaims respnsibility fr any cnsequences r liability attributable r related t any use, nnuse r interpretatin f infrmatin cntained in Blue Crss Blue Shield f Luisiana Medical Plicy Cverage Guidelines. Fee schedules, relative value units, cnversin factrs and/r related cmpnents are nt assigned by the AMA, are nt part f CPT, and the AMA is nt recmmending their use. The AMA des nt directly r indirectly practice medicine r dispense medical services. The AMA assumes n liability fr data cntained r nt cntained herein. Any use f CPT utside f Blue Crss Blue Shield f Luisiana Medical Plicy Cverage Guidelines shuld refer t the mst current Current Prcedural Terminlgy which cntains the cmplete and mst current listing f CPT cdes and descriptive terms. Applicable FARS/DFARS apply. CPT is a registered trademark f the American Medical Assciatin. Cdes used t identify services assciated with this plicy may include (but may nt be limited t) the fllwing: Cde Type Cde CPT N cdes HCPCS J3490, J3590 Page 4 f 5
Cde added eff 1/1/18: C9014 ICD-10 Diagnsis E75.4, E75.6 *Investigatinal A medical treatment, prcedure, drug, device, r bilgical prduct is Investigatinal if the effectiveness has nt been clearly tested and it has nt been incrprated int standard medical practice. Any determinatin we make that a medical treatment, prcedure, drug, device, r bilgical prduct is Investigatinal will be based n a cnsideratin f the fllwing: A. Whether the medical treatment, prcedure, drug, device, r bilgical prduct can be lawfully marketed withut apprval f the U.S. Fd and Drug Administratin (FDA) and whether such apprval has been granted at the time the medical treatment, prcedure, drug, device, r bilgical prduct is sught t be furnished; r B. Whether the medical treatment, prcedure, drug, device, r bilgical prduct requires further studies r clinical trials t determine its maximum tlerated dse, txicity, safety, effectiveness, r effectiveness as cmpared with the standard means f treatment r diagnsis, must imprve health utcmes, accrding t the cnsensus f pinin amng experts as shwn by reliable evidence, including: 1. Cnsultatin with the Blue Crss and Blue Shield Assciatin technlgy assessment prgram (TEC) r ther nnaffiliated technlgy evaluatin center(s); 2. Credible scientific evidence published in peer-reviewed medical literature generally recgnized by the relevant medical cmmunity; r 3. Reference t federal regulatins. **Medically Necessary (r Medical Necessity ) - Health care services, treatment, prcedures, equipment, drugs, devices, items r supplies that a Prvider, exercising prudent clinical judgment, wuld prvide t a patient fr the purpse f preventing, evaluating, diagnsing r treating an illness, injury, disease r its symptms, and that are: A. In accrdance with natinally accepted standards f medical practice; B. Clinically apprpriate, in terms f type, frequency, extent, level f care, site and duratin, and cnsidered effective fr the patient's illness, injury r disease; and C. Nt primarily fr the persnal cmfrt r cnvenience f the patient, physician r ther health care prvider, and nt mre cstly than an alternative service r sequence f services at least as likely t prduce equivalent therapeutic r diagnstic results as t the diagnsis r treatment f that patient's illness, injury r disease. Fr these purpses, natinally accepted standards f medical practice means standards that are based n credible scientific evidence published in peer-reviewed medical literature generally recgnized by the relevant medical cmmunity, Physician Specialty Sciety recmmendatins and the views f Physicians practicing in relevant clinical areas and any ther relevant factrs. Indicated trademarks are the registered trademarks f their respective wners. NOTICE: Medical Plicies are scientific based pinins, prvided slely fr cverage and infrmatinal purpses. Medical Plicies shuld nt be cnstrued t suggest that the Cmpany recmmends, advcates, requires, encurages, r discurages any particular treatment, prcedure, r service, r any particular curse f treatment, prcedure, r service. Page 5 f 5