SPINRAZA (NUSINERSEN)

Transcription

1 SPINRAZA (NUSINERSEN) UnitedHealthcare Oxfrd Clinical Plicy Plicy Number: PHARMACY T2 Effective Date: April 1, 2018 Table f Cntents Page INSTRUCTIONS FOR USE... 1 CONDITIONS OF COVERAGE... 1 BENEFIT CONSIDERATIONS... 1 COVERAGE RATIONALE... 2 U.S. FOOD AND DRUG ADMINISTRATION... 3 BACKGROUND... 3 APPLICABLE CODES... 4 CLINICAL EVIDENCE... 4 REFERENCES... 5 POLICY HISTORY/REVISION INFORMATION... 6 Related Plicies Nne INSTRUCTIONS FOR USE This Clinical Plicy prvides assistance in interpreting Oxfrd benefit plans. Unless therwise stated, Oxfrd plicies d nt apply t Medicare Advantage members. Oxfrd reserves the right, in its sle discretin, t mdify its plicies as necessary. This Clinical Plicy is prvided fr infrmatinal purpses. It des nt cnstitute medical advice. The term Oxfrd includes Oxfrd Health Plans, LLC all f its subsidiaries as apprpriate fr these plicies. When deciding cverage, the member specific benefit plan dcument must be referenced. The terms f the member specific benefit plan dcument [e.g., Certificate f Cverage (COC), Schedule f Benefits (SOB), /r Summary Plan Descriptin (SPD)] may differ greatly frm the stard benefit plan upn which this Clinical Plicy is based. In the event f a cnflict, the member specific benefit plan dcument supersedes this Clinical Plicy. All reviewers must first identify member eligibility, any federal r state regulatry requirements, the member specific benefit plan cverage prir t use f this Clinical Plicy. Other Plicies may apply. UnitedHealthcare may als use tls develped by third parties, such as the MCG Care Guidelines, t assist us in administering health benefits. The MCG Care Guidelines are intended t be used in cnnectin with the independent prfessinal medical judgment f a qualified health care prvider d nt cnstitute the practice f medicine r medical advice. CONDITIONS OF COVERAGE Applicable Lines f Business/ Prducts This plicy applies t Oxfrd Cmmercial plan membership. Benefit Type General Benefits Package Referral Required N (Des nt apply t nn-gatekeeper prducts) Authrizatin Required Yes 1 (Precertificatin always required fr inpatient admissin) Precertificatin with Medical Directr Review Required Yes 1 Applicable Site(s) f Service (If site f service is nt listed, Medical Directr review is required) Special Cnsideratins BENEFIT CONSIDERATIONS Spinraza (Nusinersen) Page 1 f 6 All 1 Precertificatin with review by a Medical Directr r their designee is required. Befre using this plicy, please check the member specific benefit plan dcument any federal r state mates, if applicable.

2 Sme Certificates f Cverage allw fr cverage f experimental/investigatinal/unprven treatments fr lifethreatening illnesses when certain cnditins are met. The member specific benefit plan dcument must be cnsulted t make cverage decisins fr this service. Sme states mate benefit cverage fr ff-label use f medicatins fr sme diagnses r under sme circumstances when certain cnditins are met. Where such mates apply, they supersede language in the benefit dcument r in the medical r drug plicy. Benefit cverage fr an therwise unprven service fr the treatment f serius rare diseases may ccur when certain cnditins are met. Refer t: Acquired Rare Disease Drug Therapy Exceptin Prcess. Essential Health Benefits fr Individual Small Grup Fr plan years beginning n r after January 1, 2014, the Affrdable Care Act f 2010 (ACA) requires fully insured nn-grfathered individual small grup plans (inside utside f Exchanges) t prvide cverage fr ten categries f Essential Health Benefits ( EHBs ). Large grup plans (bth self-funded fully insured), small grup ASO plans, are nt subject t the requirement t ffer cverage fr EHBs. Hwever, if such plans chse t prvide cverage fr benefits which are deemed EHBs, the ACA requires all dllar limits n thse benefits t be remved n all Grfathered Nn-Grfathered plans. The determinatin f which benefits cnstitute EHBs is made n a state by state basis. As such, when using this plicy, it is imprtant t refer t the member specific benefit plan dcument t determine benefit cverage. COVERAGE RATIONALE Spinraza (nusinersen) is prven medically necessary fr the treatment f spinal muscular atrphy (SMA) in patients wh meet ALL f the fllwing criteria: 1 Fr initial therapy, all f the fllwing: Diagnsis f spinal muscular atrphy type I, II, r III by, r in cnsultatin with, a neurlgist with expertise in the diagnsis f SMA; Submissin f medical recrds (e.g., chart ntes, labratry values) cnfirming bth f the fllwing: The mutatin r deletin f genes in chrmsme 5q resulting in ne f the fllwing: - Hmzygus gene deletin r mutatin (e.g., hmzygus deletin f exn 7 at lcus 5q13) 1,2, r - Cmpund heterzygus mutatin (e.g., deletin f SMN1 exn 7[allele 1] mutatin f SMN1 [allele 2]) Patient has at least 2 cpies f SMN2 Patient is nt dependent n either f the fllwing: Invasive ventilatin r trachestmy Use f nn-invasive ventilatin beynd use fr naps nighttime sleep Submissin f medical recrds (e.g., chart ntes, labratry values) f the baseline exam f at least ne f the fllwing exams (based n patient age mtr ability) t establish baseline mtr ability: Hammersmith Infant Neurlgical Exam Part 2 (HINE-2) 1,8,12 (infant t early childhd) Hammersmith Functinal Mtr Scale Exped (HFMSE) 1,9,13-14 Upper Limb Mdule (ULM) Test (Nn ambulatry) 1,9, Children s Hspital f Philadelphia Infant Test f Neurmuscular Disrders (CHOP INTEND) 1,8 Spinraza is prescribed by, r in cnsultatin with, a neurlgist with expertise in the treatment f SMA; Spinraza is t be administered intrathecally by, r under the directin f, healthcare prfessinals experienced in perfrming lumbar punctures; Spinraza dsing fr SMA is in accrdance with the United States Fd Drug Administratin apprved labeling: maximum dsing f 12mg fr each lading dse; Initial authrizatin will be fr n mre than 4 lading dses Fr cntinuatin therapy, all f the fllwing: Diagnsis f spinal muscular atrphy type I, II, r III by, r in cnsultatin with, a neurlgist with expertise in the diagnsis f SMA; Submissin f medical recrds (e.g., chart ntes, labratry values) cnfirming bth f the fllwing: The mutatin r deletin f genes in chrmsme 5q resulting in ne f the fllwing: - Hmzygus gene deletin r mutatin (e.g., hmzygus deletin f exn 7 at lcus 5q13) 1,2, r - Cmpund heterzygus mutatin (e.g., deletin f SMN1 exn 7[allele 1] mutatin f SMN1 [allele 2]) Patient has at least 2 cpies f SMN2 Spinraza (Nusinersen) Page 2 f 6

3 Patient is nt dependent n either f the fllwing: Invasive ventilatin r trachestmy Use f nn-invasive ventilatin beynd use fr naps nighttime sleep Submissin f medical recrds (e.g., chart ntes, labratry values) with the mst recent results (< 1 mnth prir t request) dcumenting a psitive clinical respnse frm pretreatment baseline status t Spinraza therapy as demnstrated by at least ne f the fllwing exams: HINE-2 milestnes: - One f the fllwing: Imprvement r maintenance f previus imprvement f at least 2 pint (r maximal scre) increase in ability t kick, r Imprvement r maintenance f previus imprvement f at least 1 pint increase in any ther HINE-2 milestne (e.g., head cntrl, rlling, sitting, crawling, etc.), excluding vluntary grasp - One f the fllwing: Imprvement r maintenance f previus imprvement in mre HINE mtr milestnes than wrsening, frm pretreatment baseline (net psitive imprvement), r Achieved maintained any new mtr milestnes when they wuld therwise be unexpected t d s (e.g., sit unassisted, st, walk) r HFMSE: One f the fllwing: - Imprvement r maintenance f previus imprvement f at least a 3 pint increase in scre frm pretreatment baseline, r - Achieved maintained any new mtr milestne frm pretreatment baseline when they wuld therwise be unexpected t d s r ULM: One f the fllwing: - Imprvement r maintenance f previus imprvement f at least a 2 pint increase in scre frm pretreatment baseline, r - Achieved maintained any new mtr milestne frm pretreatment baseline when they wuld therwise be unexpected t d s r CHOP INTEND: One f the fllwing: - Imprvement r maintenance f previus imprvement f at least a 4 pint increase in scre frm pretreatment baseline - Achieved maintained any new mtr milestne frm pretreatment baseline when they wuld therwise be unexpected t d s Spinraza is prescribed by, r in cnsultatin with, a neurlgist with expertise in the treatment f SMA; Spinraza is t be administered intrathecally by, r under the directin f, healthcare prfessinals experienced in perfrming lumbar punctures; Spinraza dsing fr SMA is in accrdance with the United States Fd Drug Administratin apprved labeling: maximum dsing f 12mg every 4 mnths, starting 4 mnths after the last lading dse; Reauthrizatin will be fr n mre than 3 maintenance dses (12 mnths) Spinraza is nt prven r medically necessary fr spinal muscular atrphy withut chrmsme 5q mutatins r deletins. 1 U.S. FOOD AND DRUG ADMINISTRATION (FDA) Spinraza is a survival mtr neurn-2 (SMN2)-directed antisense lignucletide indicated fr the treatment f spinal muscular atrphy (SMA) in pediatric adult patients. BACKGROUND Spinal muscular atrphy (SMA) is a rare, autsmal recessive neurmuscular disease that affects the survival f mtr neurns f the spinal crd. 2 SMA is caused by the deletin/mutatin f the SMN1 gene. 2 The estimated annual incidence f SMA is 5.1 t 16.6 cases per 100,000 live births. Apprximately 1/40 t 1/60 peple are SMA carriers, equating t 3.5 t 5.2 millin 12 t 18 millin individuals in the United States Eurpe, respectively. 3-6 SMA is characterized by the degeneratin f mtr neurns f the spinal crd, resulting in hyptnia muscle weakness. Five subtypes f SMA (0-IV) have been described based n age f symptm nset mtr functin achieved. 7 Spinraza (Nusinersen) Page 3 f 6

4 Spinraza (nusinersen) is a mdified antisense lignucletide designed t treat SMA caused by mutatins in chrmsme 5q that lead t SMN prtein deficiency. Nusinersen binds t a specific sequence in the intrn dwnstream f exn 7 f the SMN2 transcript. Using in vitr assays studies in transgenic animal mdels f SMA, nusinersen was shwn t increase exn 7 inclusin in SMN2 messenger ribnucleic acid (mrna) transcripts prductin f fulllength SMN prtein. 1 APPLICABLE CODES The fllwing list(s) f prcedure /r diagnsis cdes is prvided fr reference purpses nly may nt be all inclusive. Listing f a cde in this plicy des nt imply that the service described by the cde is a cvered r nncvered health service. Benefit cverage fr health services is determined by the member specific benefit plan dcument applicable laws that may require cverage fr a specific service. The inclusin f a cde des nt imply any right t reimbursement r guarantee claim payment. Other Plicies may apply. HCPCS Cde J2326 Injectin, nusinersen, 0.1 mg Descriptin ICD-10 Diagnsis Cde Descriptin G12.0 Infantile spinal muscular atrphy, type I [Werdnig-Hffmann] G12.1 Other inherited spinal muscular atrphy CLINICAL EVIDENCE A Phase III, multicenter, rmized, duble-blind, sham-prcedure cntrlled study assessed the clinical efficacy safety f nusinersen, administered intrathecally in 121 symptmatic infants, 7 mnths f age at the time f first dse, diagnsed with SMA (symptm nset befre 6 mnths f age). Patients were rmized 2:1 t receive either nusinersen r sham injectin. A planned interim efficacy analysis was cnducted based n patients wh died, withdrew, r cmpleted at least 183 days f treatment. Of the 82 patients included in the interim analysis, 44% were male 56% were female. Age at first treatment ranged frm 30 t 262 days (median 181). Eighty-seven (87%) f subjects were Caucasian, 2% were Black, 4% were Asian. Length f treatment ranged frm 6 t 442 days (median 261 days). Baseline demgraphics were balanced between the nusinersen cntrl grups with the exceptin f age at first treatment (median age 175 vs. 206 days, respectively). The nusinersen cntrl grups were balanced with respect t gestatinal age, birth weight, disease duratin, SMN2 cpy number (2 cpies in 98% f subjects in bth grups). Median disease duratin was 14 weeks. There was sme imbalance in age at symptm nset with 88% f subjects in the nusinersen grup 77% in the cntrl grup experiencing symptms within the first 12 weeks f life. The primary endpint assessed at the time f interim analysis was the prprtin f respnders: patients with an imprvement in mtr milestnes accrding t Sectin 2 f the Hammersmith Infant Neurlgic Exam (HINE). A treatment respnder was defined as any patient with at least a 2-pint increase (r maximal scre f 4) in ability t kick (cnsistent with imprvement by at least 2 milestnes), r at least a 1-pint increase in the mtr milestnes f head cntrl, rlling, sitting, crawling, sting r walking (cnsistent with imprvement by at least 1 milestne). T be classified as a respnder, patients needed t exhibit imprvement in mre categries f mtr milestnes than wrsening. Of the 82 patients wh were eligible fr the interim analysis, a statistically significantly greater percentage f patients achieved a mtr milestne respnse in the nusinersen grup cmpared t the sham-cntrl grup. A significantly higher percentage f infants in the nusinersen grup than in the cntrl grup had a mtr-milestne respnse (21 f 51 infants [41%] vs. 0 f 27 [0%], P<0.001), resulting in the early terminatin f the trial. In the final analysis, a significantly higher percentage f infants in the nusinersen grup than in the cntrl grup had a mtr-milestne respnse (37 f 73 infants [51%] vs. 0 f 37 [0%]), the likelihd f event-free survival was higher in the nusinersen grup than in the cntrl grup (hazard rati fr death r the use f permanent assisted ventilatin, 0.53; P = 0.005). The likelihd f verall survival was higher in the nusinersen grup than in the cntrl grup (hazard rati fr death, 0.37; P = 0.004), infants with a shrter disease duratin at screening were mre likely than thse with a lnger disease duratin t benefit frm nusinersen. The incidence severity f adverse events were similar in the tw grups. The authrs cncluded that infants with SMA wh received nusinersen were mre likely t be alive have imprvements in mtr functin than thse in the cntrl grup. The authrs suggested that early treatment may be necessary t maximize the benefit f the drug. 1, 8 A Phase III multicenter, duble-blind, rmized, sham-prcedure cntrlled study assessed the clinical efficacy safety f nusinersen in patients with later-nset SMA cnsistent with Type II SMA. Subjects were rmized 2:1 t receive intrathecal nusinersen r a sham prcedure cntrl, respectively. Inclusin criteria included diagnsis with SMA, have clinical signs symptms cnsistent with SMA at greater than 6 mnths f age, be able t sit independently, but never able t walk independently have a HFMSE scre greater than r equal t 10 less than r equal t 54 at Screening. The primary endpint is change frm baseline in HFMSE scre (at 15 mnths). Secndary Endpints are (at 15 mnths): prprtin f subjects wh achieve a 3-pint increase frm baseline in Spinraza (Nusinersen) Page 4 f 6

5 HFMSE scre, prprtin f subject that achieve any new mtr milestne, number f mtr milestnes achieved per subject, change frm baseline in Upper Limb Mdule Test, prprtin f subjects that achieve sting alne, prprtin f subject that achieve walking with assistance. In a pre-planned interim analysis, a significant difference (p = ) f 5.9 pints in HFMSE was bserved at 15 mnths between patients given nusinersen (n = 84) cmpared t the sham-prcedure cntrl (n = 42). Patients receiving nusinersen experienced a mean imprvement f 4.0 pints in the HFMSE cmpared t a mean decrease f 1.9 pints in the sham prcedure cntrl grup (5). A change f 3 pints in the HFMSE has previusly been determined t be clinically imprtant. Results fr ther endpints were cnsistent with a favrable respnse t nusinersen cmpared t sham-prcedure cntrl. Adverse events were mstly cnsidered t be related t SMA disease, cmmn events fund in the general ppulatin, r events related t the lumbar puncture prcedure. N patients discntinued the study. Nusinersen was well tlerated with a favrable safety prfile. 9 The results f the cntrlled trial in infantile-nset SMA patients were supprted by pen-label uncntrlled trials cnducted in symptmatic SMA patients wh ranged in age frm 30 days t 15 years at the time f first dse, in presymptmatic patients, wh ranged in age frm 8 days t 42 days at the time f first dse. The patients in these studies had r were likely t develp Type 1, 2, r 3 SMA. Sme patients achieved milestnes such as ability t sit unassisted, st, r walk when they wuld therwise be unexpected t d s, maintained milestnes at ages when they wuld be expected t be lst, survived t ages unexpected cnsidering the number f SMN2 gene cpies f patients enrlled in the studies. 10,11 REFERENCES The freging Oxfrd plicy has been adapted frm an existing UnitedHealthcare Pharmacy, Clinical Pharmacy Prgram that was researched, develped apprved by the UnitedHealth Grup Natinal Pharmacy & Therapeutics Cmmittee. [2018D0059D] 1. Spinraza [package insert]. Cambridge, MA: Bigen, Inc, December Markwitz JA, Singh P, Darras BT. Spinal Muscular Atrphy: A Clinical Research Update. Pediatric Neurlgy 46 (2012) Sugarman EA, Nagan N, Zhu H, et al. Pan-ethnic carrier screening prenatal diagnsis fr spinal muscular atrphy: clinical labratry analysis f >72,400 specimens. Eur J Hum Genet 2012;20: Prir TW, Snyder PJ, Rink BD, et al. Newbrn carrier screening fr spinal muscular atrphy. Am J Med Genet A Jul;152A(7): United States Census Bureau. Accessed January Wrld Ppulatin Statistics. Accessed January Lunn MR, Wang CH. Spinal muscular atrphy. Lancet Jun 21;371(9630): Finkel Rs, Mercuri E, Darras BT, et al. Nusinersen versus Sham Cntrl in Infantile-Onset Spinal Muscular Atrphy. N Engl J Med 2017;377: Inis Pharmaceuticals, Inc. A Study t Assess the Efficacy Safety f IONIS-SMN Rx in Patients with Laternset Spinal Muscular Atrphy. In: ClinicalTrials.gv [Internet]. Bethesda (MD): Natinal Library f Medicine (US) [cited 2017 Jan 6]. Available frm: NLM Identifier: NCT Finkel RS, Chiribga CA, Vajsar J, et al. Treatment f infantile-nset spinal muscular atrphy with nusinersen: a phase 2, pen-label, dse-escalatin study. Lancet Dec 17;388(10063): Chiribga CA, Swbda KJ, Darras BT, et al. Results frm a phase 1 study f nusinersen (ISIS-SMN(Rx)) in children with spinal muscular atrphy. Neurlgy Mar 8;86(10): Haataja L, Mercuri E, Regev R, et al. Optimality scre fr the neurlgic examinatin f the infant at mnths f age. J Pediatr Aug;135(2 Pt 1): Glanzman AM, O'Hagen JM, McDermtt MP, et al. Validatin f the Exped Hammersmith Functinal Mtr Scale in spinal muscular atrphy type II III. J Child Neurl. 2011;26(12): O'Hagen JM, Glanzman AM, McDermtt MP, et al. An exped versin f the Hammersmith Functinal Mtr Scale fr SMA II III patients. Neurmuscular disrders: NMD. 2007;17(9-10): Spinraza (Nusinersen) Page 5 f 6

6 POLICY HISTORY/REVISION INFORMATION Date 04/01/2018 Actin/Descriptin Updated cverage ratinale: Refrmatted/clarified cverage criterin addressing applicable diagnsis treating physician Replaced references t Hammersmith Infant Neurlgical Exam (HINE) with Hammersmith Infant Neurlgical Exam Part 2 (HINE-2) Updated supprting infrmatin t reflect the mst current clinical evidence references Archived previus plicy versin PHARMACY T2 Spinraza (Nusinersen) Page 6 f 6