P&T Committee Meeting Minutes GHP Family January 15, 2019

Transcription

1 P&T Cmmittee Meeting Minutes GHP Family January 15, 2019 Present: Bret Yarczwer, MD, MBA Chair Kristen Bender, PharmD via phne Rajneel Chhan Pharm.D. Alyssa Cilia, RPh via phne Kimberly Clark, PharmD Kristi Clarke, PharmD, MHA via phne Tricia Heitzman, PharmD. Jasn Hway, PharmD. via phne Keith Hunsicker, PharmD. Kelli Hunsicker, PharmD. via phne Steven Khelussi, PharmD via phne Phillip Krebs, R.EEG T. via phne Jamie Miller, RPh Aubrielle Prater PharmD. Kristen Scheib, PharmD. via phne William Seavey, PharmD. via phne Michael Spishck, RPh via phne Tdd Spnenberg, PharmD. Jill Stne, Pharm.D. via phne Kevin Szczecina, RPh Kelly Yelenic PharmD Matthew Seltzer student Zachary Kehler - student Absent: Kenneth Bertka, MD Beverly Blaisure, MD Hlly Bnes, PharmD Kim Castelnv, RPh Dean Christian, MD Michael Evans, RPh Patrick Fergusn, RPh, MBA Sandra Garrett, RPh, MBA Perry Meadws, MD Stephen Mscell, RPh Jnas Pearsn, RPh Richard Silbert, MD Call t Order: Dr. Bret Yarczwer called the meeting t rder at 1:02 p.m., Tuesday, January 15, Review and Apprval f Minutes: Dr. Bret Yarczwer asked fr a mtin r apprval t accept the Nvember 20, 2018 minutes as written. Kim Clark accepted the mtin and Tdd Spnenberg secnded the mtin. Nne were ppsed.

2 DRUG REVIEWS Lrbrena (lrlatinib) Review: Lrbrena indicated fr the treatment f patients with anaplastic lymphma kinase (ALK)-psitive metastatic nn-small cell lung cancer (NSCLC) whse disease has prgressed n: criztinib and at least ne ther ALK inhibitr fr metastatic disease; r alectinib as the first ALK inhibitr therapy fr metastatic disease; r Ceritinib as the first ALK inhibitr therapy fr metastatic disease. Lrbrena is the fifth ALK-targeted TKI t market, cmpeting with ther FDA-apprved ALK inhibitrs, including Xalkri (criztinib), Zykadia (ceritinib), Alecensa (alectinib), and Alunbrig (brigatinib). Lrbrena, hwever, is unique in that it was specifically designed t inhibit tumr mutatins that drive resistance t ther ALK inhibitrs and t penetrate the bld brain barrier, allwing fr use in treatment f brain metastases. Additinally, Lrbrena is the first ALK-directed targeted therapy t be apprved as a third line ptin fr patients with metastatic disease. Xalkri has pr CNS penetratin, hwever Alecensa and Alunbrig have bth shwn prmising results in the setting f brain metastases. The NCCN Panel recmmends Alecensa, Alunbrig, r Zykadia fr patients with brain lesins. Lrbrena will likely cmpete against Alecensa and Alunbrig fr ALK- psitive metastatic NSCLC with the presence f intracranial metastases. Lrbrena is supplied as 25 mg and 100 mg tablets. The recmmended dsage f Lrbrena is 100 mg rally nce daily, with r withut fd, until disease prgressin r unacceptable txicity. Tablets shuld be swallwed whle and shuld nt be chewed, crushed r split. Fr adverse reactins, the first dse reductin wuld be Lrbrena 75 mg rally nce daily and the secnd dse reductin wuld be Lrbrena 50 mg rally nce daily. Lrbrena shuld be permanently discntinued in patients wh are unable t tlerate 50 mg rally nce daily. The efficacy f Lrbrena was evaluated in Study B , a phase 2, nn-randmized, dse-ranging and activity-estimating, multi-chrt, multicenter study in ALK-psitive metastatic NSCLC patients. Frty-eight percent f patients experienced an verall respnse rate (4% cmplete and 44% partial). The median duratin f respnse was 12.5 mnths. In patients with measurable intracranial lesins, the intracranial respnse rate was 60% (21% cmplete; 38% partial) with a median duratin f respnse f 19.5 mnths. Lrbrena is cntraindicated in patients taking strng CYP3A inducers, due t ptential fr serius hepattxicity. Use f Lrbrena has been assciated with an increased risk f serius hepattxicity when used with strng CYP3A4 inducers, central nervus system (CNS) effects, hyperlipidemia, atriventricular blck, interstitial lung disease/pneumnitis, and embry-fetal txicity. In clinical trials, the mst cmmnly reprted adverse events included edema, peripheral neurpathy, cgnitive effects, dyspnea, fatigue, weight gain, arthralgia, md effects, and diarrhea. The safety and effectiveness f Lrbrena in pediatric patients have nt been established. Per NCCN, Lrbrena is indicated as a single-agent therapy fr ALK rearrangement-psitive recurrent, advanced r metastatic disease fllwing disease prgressin n first-line therapy with criztinib and subsequent therapy with alectinib, brigatinib, r ceritinib and as subsequent therapy fllwing disease prgressin n first-line therapy with alectinib, brigatinib, r ceritinib. Lrbrena is als indicated as a single therapy fr recurrent, advanced r metastatic disease in patients with ROS1 rearrangement-psitive tumrs as subsequent therapy, fllwing disease prgressin n criztinib r ceritinib. A Clinical Review including Clinical Infrmatin, Efficacy Evidence, Safety Evidence, Other Cnsideratins and a Financial Review Based n Cst Analysis were presented. Clinical Discussin: N questins r cmments. Tricia Heitzman made a mtin t accept the criteria as written. Kevin Szczecina secnded the mtin. Nne were ppsed. Financial Discussin: N questins r cmments. Tricia Heitzman made a mtin t accept the criteria as written. Kevin Szczecina secnded the mtin. Nne were ppsed.

3 Outcme: Fr GHP Family, Lrbrena will be a pharmacy benefit. It is recmmended that Lrbrena be added t the Geisinger GHP Family frmulary at the Brand tier. The fllwing prir authrizatin criteria shuld apply. Prescriptin written by r in cnsultatin with an nclgist r hematlgist AND Medical recrd dcumentatin f age greater than r equal t 18 years AND Medical recrd dcumentatin f anaplastic lymphma kinase (ALK)-psitive metastatic nn-small cell lung cancer (NSCLC) AND Medical recrd dcumentatin f disease prgressin n ne f the fllwing: Criztinib (Xalkri) and at least ne ther ALK inhibitr fr metastatic disease; OR Alectinib (Alecensa) as the first ALK inhibitr therapy fr metastatic disease; OR Ceritinib (Zykadia) as the first ALK inhibitr therapy fr metastatic disease Authrizatin Duratin: Initial apprval will be fr 12 mnths r less if the reviewing prvider feels it is medically apprpriate. Subsequent apprvals will be fr an additinal 12 mnths r less if the reviewing prvider feels it is medically apprpriate and will require medical recrd dcumentatin f cntinued disease imprvement r lack f disease prgressin. The medicatin will n lnger be cvered if the member experiences unacceptable txicity r wrsening f disease. Quantity Limit: Pharmacist nte t CSR: Authrizatin shuld be entered by HICL and nly checking the Frmulary PA required bx (n QLs need t be entered within the authrizatin). 25 mg tablet: 3 tablets per day 100 mg tablet: 1 tablet per day ZEMDRI (plazmicin) Review: Zemdri is an aminglycside anti-infective agent indicated fr the treatment f patients 18 years f age and lder with cmplicated urinary tract infectins (cuti), including pyelnephritis caused by the fllwing susceptible micrrganisms: Escherichia cli, Klebsiella pneumniae, Prteus mirabilis, and Enterbacter clacae. Due t limited clinical safety and efficacy data, Zemdri is recmmended t be reserved fr use in cuti patients wh have limited r n alternative treatment ptins. Zemdri is administered via the intravenus rute at a dse f 15mg/kg ver 30 minutes every 24 hurs fr a maximum f 7 days. Due t the nephrtxic nature f Zemdri, renal dsage adjustments may be necessary. In clinical trials, Zemdri was prven t be nn-inferir t merpenem based n the 5-day cmpsite cure rate and Test f Cure visit rate f a micrbilgical mdified intent-t-treat ppulatin. The average Zemdri length f therapy was 6 days during clinical trials. The safety prfile f Zemdri is significant fr fur black bx warnings (nephrtxicity, ttxicity, neurmuscular blckage, and fetal harm), ne cntraindicatin (knwn hypersensitivity t aminglycside prducts), and three additinal warnings and precautins (hypersensitivity reactins, including anaphylaxis, Clstridium difficile-assciated diarrhea, and ptential develpment f drug-resistant bacteria). The mst cmmn adverse effects nt already mentined included decreased renal functin, diarrhea, hypertensin, headache, nausea, vmiting, and hyptensin. Zemdri has nt been studied in patients less than the age f 18 years. The geriatric ppulatin may be subject t a higher incidence f adverse effects, which may be due t the higher prbability f having decreased renal functin. Patients with renal impairment require clse mnitring as well as dsage adjustments; hwever, there is insufficient evidence t make dsing recmmendatins fr patients with a CrCl less than 15mL/min. Ricky

4 Rampulla, a Geisinger Infectius Disease pharmacist, des nt anticipate high utilizatin f plazmicin as he expects it t be used fr nly super resistant multi-drug resistant rganisms. He anticipates patients requiring plazmicin t be hspitalized due t the cmplicated nature f the patients wh wuld qualify fr this treatment. A Clinical Review including Clinical Infrmatin, Efficacy Evidence, Safety Evidence, Other Cnsideratins and a Financial Review Based n Cst Analysis were presented. Clinical Discussin: Bret Yarczwer asked if the reasn fr drug failures (i.e., was it resistance, etc) was knwn? Respnse was that it was nt specified in the trial. N ther questins r cmments. Kevin Szczecina made a mtin t accept the recmmendatins as presented. Kelly Yelenic secnded the mtin. Nne were ppsed. Financial Discussin: N questins r cmments. Tdd Spnenberg made a mtin t accept the recmmendatins as presented. Kim Clark secnded the mtin. Nne were ppsed. Outcme: Fr GHP Family, Zemdri will be a medical benefit requiring prir authrizatin.the fllwing prir authrizatin criteria shuld apply. Age f 18 years r greater AND Medical recrd dcumentatin f a diagnsis f cmplicated urinary tract infectins (cuti) including pyelnephritis caused by the fllwing susceptible micrrganisms: Escherichia cli, Klebsiella pneumniae, Prteus mirabilis, and Enterbacter clacae AND Medical recrd dcumentatin f culture and sensitivity shwing the patient s infectin is nt susceptible t ALL alternative antibitic treatments OR a dcumented histry f previus intlerance t r cntraindicatin t ALL ther antibitics shwn t be susceptible n the culture and sensitivity OR If initiated during an inpatient say: Medical recrd dcumentatin f a culture and sensitivity shwing the patient s infectin is nt susceptible t alternative antibitic treatments OR a dcumented histry f previus intlerance t r cntraindicatin t ther antibitics shwn t be susceptible n the culture and sensitivity Authrizatin Duratin: up t a maximum f 7 days Other Recmmendatins: Vabmere (Merpenem/Vabrbactam Injectin): T ensure cnsistency between anti-infective plicies, it is recmmended that the fllwing criteria be added t the respective Vabmere plicies fr all lines f business: OR If initiated during an inpatient say: Medical recrd dcumentatin f a culture and sensitivity shwing the patient s infectin is nt susceptible t alternative antibitic treatments OR a dcumented histry f previus intlerance t r cntraindicatin t ther antibitics shwn t be susceptible n the culture and sensitivity Other Recmmendatins: Sivextr (Tedizlid): T ensure cnsistency between anti-infective plicies and lines f business, it is recmmended that the fllwing be added t (r replace the existing inpatient stay criteria) the respective Sivextr plicies fr all lines f business: OR

5 If initiated during an inpatient say: Medical recrd dcumentatin f a culture and sensitivity shwing the patient s infectin is nt susceptible t alternative antibitic treatments OR a dcumented histry f previus intlerance t r cntraindicatin t ther antibitics shwn t be susceptible n the culture and sensitivity LOKELMA (sdium zircnium cyclsilicate) Review: Lkelma is a ptassium binder indicated fr the treatment f hyperkalemia in adults. Lkelma is nt t be used in emergency treatment fr life threatening hyperkalemia. Lkelma is dsed as 10 g three times a day fr up t 48 hurs as a starting dse, then as 5 g every ther day t 15 g nce daily fr maintenance treatment. Lkelma can be stred at rm temperature cmpared t Veltassa, which needs t be stred in the refrigeratr. Other medicatins with ph dependent slubility must be administered at least 2 hurs befre r 2 hurs after Lkelma administratin. Lkelma has been shwn t significantly decrease serum ptassium in the first 48 hurs and maintain nrmal levels during the extended phase. Lkelma des nt have any black bx warnings r cntraindicatins. It has a warning fr patients with mtility disrders due t pssible gastrintestinal adverse events. The adverse events f Lkelma include edema and hypkalemia. Lkelma is safe in pregnancy, lactatin, and geriatrics, hwever safety in pediatrics has nt been established. UpTDate recmmends the use f dietary mdificatin, diuretics (if therwise apprpriate), and reversal f factrs that can cause hyperkalemia (e.g., NSAIDs, hypvlemia, RAAS inhibitrs) befre using a gastrintestinal catin exchanger, like Lkelma and Veltassa fr patients withut an urgent need t lwer their ptassium levels (mst patients with serum ptassium levels < 6.5 meq/l). Veltassa and Lkelma are recmmended ver SPS fr chrnic hyperkalemia due t multiple warnings and cntraindicatins with SPS, particularly intestinal necrsis, which may be fatal. A Clinical Review including Clinical Infrmatin, Efficacy Evidence, Safety Evidence, Other Cnsideratins and a Financial Review Based n Cst Analysis were presented. Fr geriatric members, n verall difference in safety r effectiveness were bserved between elderly and yunger patients. Clinical Discussin: N cmments r questins. Tricia Heitzman made a mtin t accept the recmmendatins as written. Keith Hunsicker secnded the mtin. Nne were ppsed Financial Discussin: N cmments r questins. Rajneel Chhan made a mtin t accept the recmmendatins as written. Tricia Heitzman secnded the mtin. Nne were ppsed. Outcme: Lkelma is a pharmacy benefit and shuld be added t the Brand tier f the GHP Family frmulary at this time. The fllwing prir authrizatin criteria shuld apply. - Medical recrd dcumentatin f a diagnsis f mild t mderate hyperkalemia (greater than r equal t 5.1 meq/l and less than 6.5 meq/l) AND - Medical recrd dcumentatin f age greater than r equal t 18 years AND - Medical recrd dcumentatin that attempt has been made t identify and crrect the underlying cause f the patient s hyperkalemia OR ratinale as t why the underlying cause cannt be crrected AND - Fr mild hyperkalemia (serum ptassium greater than r equal t 5.1 meq/l and less than 5.5 meq/l): Medical recrd dcumentatin that a lw ptassium diet has been tried and was unsuccessful at cntrlling the patient s serum ptassium level AND - Medical recrd dcumentatin f a therapeutic failure n, intlerance t, r cntraindicatin t lp diuretic r thiazide diuretic therapy

6 Quantity Limit:5 g packet: 1 packet daily; 10 g packet: 34 packets/30 days LUMOXITI (mxetummab pasudtx-tdfk) Review: Lumxiti is a CD22-directed cyttxin indicated fr the treatment f adult patients with relapsed r refractry hairy cell leukemia (HCL) wh received at least tw prir systemic therapies, including treatment with a purine nucleside analg (PNA). Hairy Cell Leukemia (HCL) is a rare frm f chrnic lymphcytic leukemia (CLL), a cancer that riginates in the bne marrw. HCL affects abut 1,000 peple per year in the United States and cmprises abut 2% f all leukemias. Apprximately 40% f patients relapse after respnding t initial treatment with a purine nucleside analg after being in remissin fr 10 t 15 years. Lumxiti marks the first new treatment ptin fr patients with hairy cell leukemia in ver 20 years. Lumxiti is a CD22-directed cyttxin that wrks by delivering a bund txic substance directly t the cancer cells, limiting its effects n healthy cells by virtue f its targeted delivery. This is the first drug f this type apprved fr the treatment f HCL. Lumxiti is given via intravenus infusin n Days 1, 3, and 5 f each 28-day cycle, fr a maximum f 6 cycles, r until disease prgressin r unacceptable txicity. Safety and Efficacy were established in a phase 3, single arm, pen-label, multicenter trial f Lumxiti in relapsed r refractry HCL. Patients had a diagnsis f HCL and had received prir treatment with at least tw systemic therapies, including ne purine nucleside analg (PNA). Efficacy was shwn with a Cmplete Respnse (CR) rate f 30% (24/80 patients; 95% CI: 20-41%). Cmplete Respnse was cnfirmed by maintenance f hematlgic remissin (hemglbin 11 g/dl, neutrphils 1,500/mm3, and platelets 100,000/mm3 withut transfusins r grwth factr fr at least 4 weeks) mre than 180 days after internal review cmmittee assessed CR. Lumxiti has a black bx warning fr the risk f capillary leak syndrme (CLS) and hemlytic uremic syndrme (HUS), which can be life-threatening. There are additinal warnings and precautins fr renal txicity, infusin related reactins, and electrlyte abnrmalities. The mst cmmn adverse reactins ccurring in >20% f patients are infusin related reactins, edema, nausea, fatigue, headache, pyrexia, cnstipatin, anemia, and diarrhea. The mst cmmn labratry abnrmalities ccurring in > 50% f patients are hypalbuminemia, hypcalcemia, hypphsphatemia, and increased creatinine, ALT and AST. NCCN Guidelines cnsider purine nucleside analgs (PNA) (e.g. cladribine, pentstatin) first-line therapy fr initial treatment f previusly untreated classic HCL. Patients with disease relapse after > 2 years after achieving CR t initial PNA may benefit frm retreatment with the same PNA with r withut rituximab. Other ptins include treatment with an alternative PNA with r withut rituximab r rituximab mntherapy (if unable t receive PNA). Optins fr patients with disease relapse within 2 years after achieving CR t initial therapy, r wh d nt attain CR n first-line therapy, include enrllment in clinical trials, treatment with interfern alfa, alternate PNA + rituximab mntherapy (if unable t receive PNA), and vemurafenib. Fr further disease prgressin f relapsed r refractry HCL, secnd-line therapy ptins include enrllment in clinical trials, ibrutinib r vemurafenib + rituximab r Lumxiti. A Clinical Review including Clinical Infrmatin, Efficacy Evidence, Safety Evidence, and Other Cnsideratins and a Financial Review Based n Cst Analysis were presented.

7 Clinical Discussin: Keith Hunsicker suggested amending the reauthrizatin requirement beynd six mnths t require literature supprt fr dsing that exceeds prduct labeling. Keith Hunsicker made a mtin t accept the recmmendatins as amended. Rajneel Chhan secnded the mtin. Nne were ppsed Financial Discussin: N cmments r questins. Kevin Szczecina made a mtin t accept the recmmendatins as written. Tdd Spnenberg secnded the mtin. Nne were ppsed Outcme: Lumxiti will be a medical benefit requiring prir authrizatin as utlined belw fr Geisinger GHP Family members. Hairy Cell Leukemia Prescriptin is written by a hematlgist/nclgist AND Medical recrd dcumentatin that member is 18 years f age r lder AND Medical recrd dcumentatin f a diagnsis f relapsed r refractry hairy cell leukemia (HCL) AND Medical recrd dcumentatin that member has received at least tw prir systemic therapies, ne f which must be a purine nucleside analg (e.g., cladribine, pentstatin (Nipent), etc.) Authrizatin Duratin: Initial apprval will be limited t 6 cycles (6 mnths) r less if the reviewing prvider feels it is medically necessary. Subsequent apprval fr treatment past 6 cycles (6 mnths) will require dcumentatin f well-cntrlled, peer-reviewed literature with evidence t supprt this request. ONPATTRO (patisiran) Review: Onpattr is indicated fr the treatment f the plyneurpathy f hereditary transthyretin-mediated amylidsis in adults. Onpattr is the first apprved agent fr the treatment f hereditary transthyretin amylidsis (hattr), a rare, genetic, and prgressive multi-rgan disrder. Onpattr is als the first FDA apprval f a new class f drugs called small interfering ribnucleic acid (sirna) treatment, which wrk by silencing a prtin f the RNA invlved in causing the disease. Onpattr causes degradatin f mutant and wild-type TTR mrna thrugh RNA interference, which results in a reductin in serum TTR prtein and TTR prtein depsits in tissues. Onpattr is available as a lipid cmplex slutin fr intravenus infusin and is supplied as a 10 mg/5 ml single-dse vial. Onpattr requires administratin nly by a healthcare prfessinal. Dsing is based n actual bdy weight. Fr patients weighing less than 100 kg, the recmmended dsage is 0.3 mg/kg nce every 3 weeks. Fr patients weighing 100 kg r mre, the recmmended dsage is 30 mg nce every 3 weeks. All patients shuld receive premedicatins (crticsterid, acetaminphen, H1 blcker, H2 blcker) 60 minutes prir t Onpattr t reduce the risk f infusin-related reactins. The safety and efficacy fr Onpattr was demnstrated in a Phase 3 randmized, duble-blind, placebcntrlled clinical trial in adult patients with plyneurpathy caused by hattr. T be included in the clinical trial patients had t have a diagnsis f hattr amylidsis with plyneurpathy caused by an TTR mutatin and neurpathy impairment scre (NIS) f Abut half f the patients were previusly treated with tafamidis r diflunisal. Patients wh were wheelchair-bund r bedridden were excluded frm the trial. Patients with a histry f liver transplant, thse planning t underg a liver transplant, r thse with NYHA class III r IV heart failure were excluded. Patients were randmized in a 2:1 rati t receive Onpattr 0.3 mg/kg (N=148) r placeb (N=77) intravenusly nce every 3 weeks fr 18 mnths. The change frm baseline t mnth 18 n bth endpints met statistical significance in favr f Onpattr, as well as did ther secndary endpints. Patients wh received Onpattr had similar imprvements relative t placeb in mnis+7 and Nrflk QL-DN acrss all subgrups f patients (age, sex, race, regin, mutatin type, NIS scre, prir tafamidis r diflunisal use, and disease stage). The effects were seen as early as 9 mnths. The mnis +7 is an bjective assessment f neurpathy that measures

8 deficits in cranial nerve functin, muscle strength, and reflexes, as well as pstural bld pressure, quantitative sensry testing, and peripheral nerve electrphysilgy (higher scres indicate a greater severity f disease). The QL-DN scre is a patient-reprted assessment that evaluates the experience f neurpathy in functining, largefiber/small-fiber neurpathy, activities f daily living, and autnmic neurpathy (higher scres indicate a greater impairment). There were changes in BMI and gait speed that significantly favred Onpattr. Patients receiving Onpattr experienced a statistically significant reductin in autnmic symptms such as dizziness, cnstipatin, diarrhea, vmiting, and incntinence. Thse receiving Onpattr saw a significant benefit in the ability t perfrm activities f daily living and everyday functin (eating, bathing, dressing, mtr strength, standing, mbility, selfcare, usual activities, and pain/discmfrt and anxiety/depressin. The plyneurpathy disability scre was stable in 65% f patients and imprved in 8% f patients receiving Onpattr. This included transitin frm assisted t unassisted walking. Amng patients whse plyneurpathy disability scre wrsened at 18 mnths, wrsening by mre than 1 level was bserved in 17% f patients in the patisiran grup as cmpared t 50% in the placeb grup. Patisiran was als assciated with better cardiac structure and functin cmpared t placeb. There are n black bx warnings r cntraindicatins t Onpattr. There are warnings fr infusin-related reactins and reduced serum vitamin A levels. Supplementatin f recmmended daily allwances f vitamin A is advised fr patients taking Onpattr. Upper respiratry tract infectins and infusin-related reactins were the mst cmmn adverse reactins. Fur serius adverse reactins f atriventricular (AV) heart blck (2.7%) ccurred in Onpattr-treated patients, including 3 cases f cmplete AV blck. N serius adverse reactins f AV blck were reprted in placeb-treated patients. Safety and effectiveness in pediatric patients have nt been established. Nathan Sauers, clinical pharmacist at Geisinger, had sme discussins with cardilgists regarding the use f Onpattr in patients with wild type ATTR cardiac amylid. At this time, they believe that the apprval fr wild type ATTR cardiac amylid is years away. Until further studies are cmpleted, they believe the FDA apprved indicatin is the mst apprpriate use fr Onpattr at this time. Dan Grassi, neurlgy clinical pharmacist at Geisinger, had discussins regarding Onpattr with Dr, Friedenberg and Dr. Avila. They agree that treatment f Onpattr shuld be avided in patients that are wheelchair bund r bedridden, based n the inclusin criteria in the APOLLO study. Patients with TTR gentype with hattr amylidsis neurpathy (cnfirmed via genetic testing) with FAP stage 1-2 and PND scres I-IIIb shuld meet criteria fr treatment. Fr these patients, initial treatment wuld be Onpattr, nt diflunisal. A Clinical Review including Clinical Infrmatin, Efficacy Evidence, Safety Evidence, and Other Cnsideratins and a Financial Review Based n Cst Analysis were presented. Clinical Discussin: N cmments r questins. Tricia Heitzman made a mtin t accept the recmmendatins as written. Kevin Szczecina secnded the mtin. Nne were ppsed Financial Discussin: Bret Yarczwer asked if it was knwn if Geisinger Medical Center was able t btain the medicatin. It was nt knwn at this time. N ther cmments r questins. Tricia Heitzman make a mtin t accept the recmmendatins as written. Kevin Szczecina secnded the mtin. Nne were ppsed Outcme: Onpattr will be cvered as a medical benefit fr Geisinger GHP Family members. The fllwing prir authrizatin criteria shuld apply. Prescriptin written by r in cnsultatin with a neurlgist, specialist at a hereditary transthyretin-mediated amylidsis treatment center, r geneticist AND Medical recrd dcumentatin f age greater than r equal t 18 years AND Medical recrd dcumentatin f diagnsis f hereditary transthyretin-mediated amylidsis as cnfirmed by all f the fllwing: Bipsy f tissue/rgan t cnfirm amylid presence AND Immunhistchemistry r mass spectrscpy t differentiate ATTR amylidsis frm amylid light-chain amylidsis AND

9 Genetic testing t differentiate between hereditary and wild-type ATTR amylidsis AND Medical recrd dcumentatin f Onpattr being used t treat plyneurpathy AND Medical recrd dcumentatin f familial amylid plyneurpathy (FAP) stage 1-2 and/r plyneurpathy disability scre f I, II, IIIA, r IIIB AND Medical recrd dcumentatin that Onpattr will nt be used in cmbinatin with ther RNA interference treatment Nte: FAP stage: 1-unimpairmend ambulatin 2- assistance with ambulatin 3- wheelchair-bund r bedridden Plyneurpathy disability scre: I- preserved walking, sensry disturbances II- impaired walking withut need fr stick/crutches IIIa- walking with 1 stick/crutch IIIb- walking with 2 sticks/crutches IV-wheelchair-bund r bedridden Authrizatin Duratin: Initial apprval will be fr 12 mnths r less if the reviewing prvider feels it is medically apprpriate. Subsequent apprvals will be fr an additinal 12 mnths r less if the reviewing prvider feels it is medically apprpriate. The medicatin will n lnger be cvered if the member prgresses t FAP stage 3 and/r plyneurpathy disability scre IV (wheelchair-bund r bedridden). Quantity Limit: 15 ml per 21 days PLENVU (plyethylene glycl 3350, sdium ascrbate, sdium sulfate, ascrbic acid, sdium chlride and ptassium chlride fr ral slutin) Review: Plenvu (plyethylene glycl 3350, sdium ascrbate, sdium sulfate, ascrbic acid, sdium chlride and ptassium chlride fr ral slutin) is an smtic laxative indicated fr cleansing f the cln in preparatin fr clnscpy in adults. Plenvu (plyethylene glycl 3350, sdium ascrbate, sdium sulfate, ascrbic acid, sdium chlride and ptassium chlride fr ral slutin) is supplied as a white t yellw pwder fr recnstitutin. Tw dses f Plenvu are required fr a cmplete preparatin fr clnscpy, using a Tw-Day r One- Day dsing regimen. Plenvu must be recnstituted in water prir t ingestin. Additinal clear liquids must be cnsumed after each dse f Plenvu in bth dsing regimens. Patients shuld be instructed t nt take ral medicatins within 1 hur f starting each dse. The Tw-Day Split-Dsing Regimen cmmences in the evening f the day befre the clnscpy. Instruct adult patients that n the day befre the clinical prcedure, they can cnsume a light breakfast fllwed by a light lunch, which must be cmpleted at least 3 hurs prir t the start f the first Plenvu dse. Instruct patients t take tw separate dses in cnjunctin with clear liquids. The One-Day Mrning Dsing Regimen cmmences in the mrning f the day f the clnscpy. Instruct adult patients that n the day befre the clinical prcedure, they can cnsume a light breakfast fllwed by a light lunch, and clear brth sup and/r plain ygurt fr dinner, which shuld be cmpleted by apprximately 8 pm. Instruct patients t take tw separate dses in cnjunctin with clear liquids.

10 Apprval was based n multiple Phase III clinical trials, including the NOCT study, a multicenter, randmized, parallel-grup trial that enrlled 540 patients acrss tw arms. The study cmpared Plenvu with a trisulfate bwel cleansing slutin (sdium sulfate, ptassium sulfate, and magnesium sulfate fr ral slutin [Suprep]) using a 2- day split-dsing regimen in adults. Participants met bth primary endpints, achieving nninferir verall bwel cleansing success and excellent plus gd cleansing f the ascending cln accrding t the Harefield Cleansing Scale. The Phase III prgram als included tw clinical trials in Eurpe. The MORA study cmpared Plenvu t a standard 2-liter PEG with ascrbate (sdium sulfate, sdium chlride, ptassium chlride, sdium ascrbate, and ascrbic acid fr ral slutin [Mviprep]) using a 2-day evening/mrning split-dsing regimen and a 1-day, mrning-nly split-dsing regimen in adults. The study met bth f its primary endpints: when administered using either dsing regimen, Plenvu was as effective as Mviprep in achieving verall bwel cleansing success and superir t Mviprep in achieving high-quality cleansing f the ascending cln. In the ther Eurpean study, DAYB, Plenvu achieved statistically significant imprvements in adequate cleansing rates using a day-befre-nly dsing regimen in adults when cmpared with a sdium picsulfate and magnesium salt slutin. The mst cmmn adverse reactins (>2% f participants) are nausea, vmiting, dehydratin, and abdminal pain/discmfrt. Patients shuld stp drinking Plenvu temprarily r drink each prtin at lnger intervals if they develp severe abdminal discmfrt r distentin A Clinical Review including Clinical Infrmatin, Efficacy Evidence, Safety Evidence, and Other Cnsideratins and a Financial Review Based n Cst Analysis were presented. Clinical Discussin: Keith Hunsicker made a mtin t accept the recmmendatins as written. Tdd Spnenberg secnded the mtin. Nne were ppsed Financial Discussin: N cmments r questins. Tricia Heitzman made a mtin t accept the recmmendatins as written. Tdd Spnenberg secnded the mtin. Nne were ppsed Outcme: Plenvu will be nn-frmulary fr Geisinger GHP Family members. MULPLETA (lusutrmbpag) Review: Mulpleta (lusutrmbpag) jins Dptelet (avatrmbpag) as the secnd FDA-apprval ral thrmbpietin receptr agnist (TPO-RA) apprved specifically fr use in chrnic liver disease (CLD) adult patients with thrmbcytpenia anticipating an invasive prcedure. Prmacta (eltrmbpag) is anther ral TPO-RA used fr the treatment f thrmbcytpenia; hwever, it is indicated t allw initiatin and maintenance f interfern treatment in hepatitis C patients with lw platelets. It is anticipated that Mulpleta will share the same place in therapy as Dptelet. Mulpleta prvides an additinal treatment ptin fr adult CLD patients with thrmbcytpenia and it may ffer several advantages ver Dptelet: Dptelet s dsing is based n a patient s platelet cunt whereas Mulpleta has a fixed dse fr all patients. Additinally, Mulpleta s ne-tablet-per-day dsing may be a mre desirable ptin fr patients with a high pill burden, as patients n Dptelet may be required t take up t 3 tablets per day. Hwever, Mulpleta is taken fr a lnger duratin (7 days) cmpared t Dptelet (5 days). The efficacy f Mulpleta was evaluated in L-PLUS 1 and L-PLUS 2; tw randmized, multicenter, dubleblind, placeb-cntrlled clinical trials. T be included in the trials, patients had t have CLD with thrmbcytpenia defined as <50 x 10 9 platelets/l with a scheduled prcedure. Patients were randmized 1:1 t

11 receive 3 mg f Mulpleta r placeb nce daily fr up t 7 days. Randmizatin was stratified by prcedure: liver ablatin/cagulatin r ther prcedure, with the majrity (57% in L-PLUS 1 and 98% in L-PLUS 2) underging a prcedure ther than liver ablatin/cagulatin. Patients were excluded if their prcedure included lapartmy, thractmy, pen-heart surgery, cranitmy, r rgan resectin. Patients were als excluded if they had a histry f splenectmy, partial splenic emblizatin, thrmbsis, Child-Pugh class C liver disease, absence f hepatpetal bld flw, r a prthrmbtic cnditin ther than CLD. The primary endpint was met in bth L-PLUS 1 and 2, and mre patients in the Mulpleta grup shwed respnse in platelet increase cmpared t their crrespnding placeb grup. There are n black bx warnings r cntraindicatins assciated with the use f Mulpleta. Safety and effectiveness in pediatric patients have nt been established. Clinical studies f Mulpleta did nt include sufficient numbers f subjects aged 65 and ver t determine whether they respnd differently frm yunger subjects. A ppulatin pharmackinetic analysis did nt find a clinically meaningful effect f mild) and mderate renal impairment n the pharmackinetics f Mulpleta. N clinically significant differences in the pharmackinetics f lusutrmbpag were bserved based n mild t mderate hepatic impairment. The mean bserved Mulpleta Cmax and AUC0 τ decreased by 20% t 30% in patients with severe hepatic impairment cmpared t patients with Child Pugh class A and class B liver disease. Hwever, the ranges fr Cmax and AUC0 τ verlapped amng patients with mild, mderate, and severe liver disease. There are n dsage adjustments due t renal r hepatic insufficiency prvided in the manufacturer's labeling. Sandra Gaines, PharmD, Clinical Pharmacist at Geisinger Medical Center was cnsulted, and she stated there is very little utilizatin f Mulpleta r Dptelet and she des nt prefer ne agent ver the ther. A Clinical Review including Clinical Infrmatin, Efficacy Evidence, Safety Evidence, and Other Cnsideratins and a Financial Review Based n Cst Analysis were presented. Clinical Discussin: Tdd Spnenberg made a mtin t accept the recmmendatins as written. Tricia Heitzman secnded the mtin. Nne were ppsed. Financial Discussin: N cmments r questins. Tricia Heitzman made a mtin t accept the recmmendatins as written. Tdd Spnenberg secnded the mtin. Nne were ppsed. Outcme: Mulpleta is a pharmacy benefit and shuld be added t the Geisinger GHP Family Frmulary n the Brand tier requiring prir authrizatin. The fllwing prir authrizatin criteria shuld apply: - Medical recrd dcumentatin f thrmbcytpenia in adult patients with chrnic liver disease AND - Medical recrd dcumentatin f member s age being 18 years ld AND - Medical recrd dcumentatin f a platelet cunt f < 50 x 10 9 /L measured within the past 30 days AND - Medical recrd dcumentatin f a planned invasive prcedure t be perfrmed 8-14 days after initiatin date fr Mulpleta treatment AND - Medical recrd dcumentatin that the prescriptin fr Mulpleta is written by r in cnsultatin with a hematlgist, gastrenterlgist, hepatlgist, immunlgist, transplant specialist, r endcrinlgist AND - Medical recrd dcumentatin that the member is nt receiving ther TPO-RAs (Nplate/rmiplstim, Prmacta/eltrmbpag) AND - Medical recrd dcumentatin f the crrect dse being used (3 mg rally nce daily fr 7 days) Authrizatin Duratin: 30 days Quantity Limit: 7 tablets per fill, ne fill per Rx.

12 Additinal frmulary recmmendatin: Add the fllwing criterin t the Dptelet plicy fr all lines f business: Medical recrd dcumentatin f therapeutic failure n, intlerance t r cntraindicatin t Mulpleta ILUMYA (tildrakizumab-asmn) Review: Ilumya is an IgG1/k mnclnal antibdy indicated fr the treatment f adults with mderate t severe plaque psriasis wh are candidates fr systemic therapy r phttherapy, which jins 12 ther bilgic agents used t treat the same indicatin. Ilumya must be prvider administered and is dsed as a subcutaneus injectin at weeks 0, 4, and every 12 weeks thereafter. While the frequency f dsing makes Ilumya preferable amng sme f the alternatives, the requirement f prvider administratin may be a drawback fr patients wh prefer selfadministratin. In clinical trials, Ilumya cnsistently utperfrmed placeb and etanercept in the achievement f PASI (Psriasis Area and Severity Index) 75 imprvement, PASI 90 imprvement, PASI 100 imprvement, clear r minimal PGA (Physician s Glbal Assessment), and DLQI (Dermatlgy Life Quality Index) scre at week 12. These results were maintained ut t week 28 and were als maintained when switching frm placeb t tildrakizumab. Switching frm etanercept t tildrakizumab was nt tested. At week 28, patients respnding t tildrakizumab were re-randmized t an additinal 36 weeks f either Ilumya r placeb. 84% f patients wh cntinued t receive Ilumya maintained PASI 75 cmpared t 22% f patients wh received placeb at week % f patients wh cntinued t receive Ilumya cmpared t 14% f patients wh received placeb maintained a PGA f 0 r 1 frm week 28 t 64. The median time t lss f PASI 75 in patients wh transitined frm tildrakizumab t placeb was abut 20 weeks. The median time t lss f PGA f 0 r 1 in these patients was abut 16 weeks. The safety prfile f Ilumya is relatively benign. Ilumya s warnings and precautins are significant fr hypersensitivity reactins, infectins, and tuberculsis. The mst cmmn adverse reactins included upper respiratry infectins, injectin site reactins, and diarrhea. Guidelines generally reserve bilgic treatments fr patients with extensive disease r if patients d nt have extensive disease but have ther risk factrs such as pr quality f life r ineffectiveness f ther therapies. The American Academy f Dermatlgy guidelines nly discuss the rle f IL-12/23 blckade in the pathphysilgy f psriasis. The guidelines have nt been updated since the intrductin f these agents t make recmmendatins n nn-tnf bilgics. The Geisinger Psriasis PrvenCare Pathway generally reserves bilgic treatment fr patients with extensive disease after failure f light therapy and ral therapies and fr patients with less extensive disease after failure f tpical, light, and ral therapies. The pathway prefers Humira as a first-line bilgic and Csentyx as a secnd-line bilgic due t the lack f clear evidence that ne therapy is mre clinically significant than anther. A Clinical Review including Clinical Infrmatin, Efficacy Evidence, Safety Evidence, and Other Cnsideratins and a Financial Review Based n Cst Analysis were presented. Clinical Discussin: N cmments r questins. Kim Clark made a mtin t accept the recmmendatins as written. Kelly Yelenic secnded the mtin. Nne were ppsed. Financial Discussin: N cmments r questins. Kevin Szczecina made a mtin t accept the recmmendatins as written. Tdd Spnenberg Heitzman secnded the mtin. Nne were ppsed.

13 Outcme: Fr GHP Family, Ilumya will be a medical benefit and shuld nt be added t the Geisinger GHP Family pharmacy frmulary. A prir authrizatin with the fllwing criteria shuld apply. 1. Prescribed by a dermatlgist AND 2. Medical recrd dcumentatin that the patient is 18 years f age r lder AND 3. Medical recrd dcumentatin f a diagnsis f mderate t severe plaque psriasis characterized by greater than r equal t 5% bdy surface area invlved r disease affecting crucial bdy areas such as the hands, feet, face, r genitals AND 4. Medical recrd dcumentatin that Ilumya is nt being used cncurrently with a TNF blcker r ther bilgic agent AND 5. Medical recrd dcumentatin f an inadequate respnse t, cntraindicatin t, r failure n at least 3 mnths f Humira AND Csentyx Authrizatin Duratin: Apprval will be given fr an initial duratin f six (6) mnths. Fr cntinuatin f cverage, medical recrd dcumentatin f clinical imprvement r lack f prgressin in the signs and symptms f the treated indicatin at six (6) mnths f Ilumya therapy is required. After the initial six (6) mnth apprval, subsequent apprvals fr cverage will be fr a duratin f ne (1) year. Reevaluatin f cverage will be every ne (1) year requiring medical recrd dcumentatin f cntinued r sustained imprvement in the signs and symptms f the treated indicatin while n Ilumya therapy. GALAFOLD (migalastat) Review: Galafld is an alpha-galactsidase A (alpha-gal A) pharmaclgical chaperne indicated fr the treatment f adults with a cnfirmed diagnsis f Fabry disease and an amenable galactsidase alpha gene (GLA) variant based n in vitr assay data. Galafld is the first ral medicatin fr the treatment f Fabry disease. As an alpha-gal A pharmaclgical chaperne, Galafld reversibly binds t the active site f the alpha-gal A prtein. This selective binding stabilizes and caxes alpha-gal A int its prper cnfrmatin, enabling augmented enzymatic functin f residual alpha-gal A and, thereby, clearance f glycsphinglipids including GL-3. The management f Fabry disease currently centers arund enzyme replacement therapy (ERT) with Fabrazyme (agalsidase beta), a recmbinant frm f the alpha-gal A enzyme. Fabrazyme can be used in all variants f Fabry disease fr the treatment f bth children (8 years and lder) and adults. In cntrast, Galafld is nly indicated in a subset f adult patients with amenable GLA mutatins (with FDA apprval fr 348 amenable variants) as Galafld wrks by stabilizing and enhancing the activity f residual alpha-gal A. Galafld ffers the advantage f being an ral medicatin with n significant safety cncerns, whereas Fabrazyme requires administratin via intravenus infusin by a healthcare prfessinal and is assciated with a risk f anaphylactic and infusin reactins. Galafld is available as 123 mg capsules in a blister pack cntaining 14 capsules fr a 28-day supply. The recmmended dsage f Galafld is 123 mg rally nce every ther day (Galafld shuld nt be taken n tw cnsecutive days). Dses shuld be taken n an empty stmach. The efficacy and safety f Galafld was evaluated in a 6-mnth, randmized, duble-blind, placebcntrlled trial fllwed by a 6-mnth, pen-label treatment phase and a 12-mnth, pen-label extensin phase. In the initial 6-mnth phase, a ttal f 67 participants were randmized in a 1:1 rati t receive either placeb r Galafld at the recmmended dsing regimen. In the 6-mnth, pen-label phase, all patients were treated with Galafld. Of the 67 enrlled patients, 50 had amenable GLA variants based n the in vitr amenability assay. The primary efficacy endpint f the average number f GL-3 inclusins per kidney interstitial capillary (KIC) in renal bipsy samples was assessed by light micrscpy befre and after treatment. Efficacy was evaluated after 6 mnths

14 f treatment. A greater prprtin f patients receiving Galafld experienced 50% reductin frm baseline in the average number f GL-3 inclusins per KIC. Patients with nn-amenable GLA variants had n change frm baseline in the average number f GL-3 inclusins per KIC at 6 mnths. There are n black bx warnings, cntraindicatins, r warnings and precautins assciated with the use f Galafld. The safety and effectiveness f Galafld have nt been established in pediatric patients. A Clinical Review including Clinical Infrmatin, Efficacy Evidence, Safety Evidence, and Other Cnsideratins and a Financial Review Based n Cst Analysis were presented. Clinical Discussin: N cmments r questins. Kevin Szczecina made a mtin t accept the recmmendatins as written. Kelly Yelenic secnded the mtin. Nne were ppsed. Financial Discussin: N cmments r questins. Tdd Spnenberg made a mtin t accept the recmmendatins as written. Keith Hunsicker secnded the mtin. Nne were ppsed. Outcme: Galafld will be a pharmacy benefit and shuld nt be added t the Geisinger GHP Family pharmacy frmulary. The fllwing prir authrizatin criteria will apply: Patient is 18 years f age r lder AND Prescriptin written by r in cnsultatin with a geneticist, nephrlgist, cardilgist, r a physician wh specializes in the treatment f Fabry disease AND Medical recrd dcumentatin f a diagnsis f Fabry disease as cnfirmed by ne f the fllwing: Enzyme assay indicating deficiency f Alpha Gal-A (if male) OR Genetic test dcumenting galactsidase alpha gene mutatin AND Medical recrd dcumentatin f in vitr assay data cnfirming the presence f an amenable galactsidase alpha gene (GLA) variant, in accrdance with the FDA-apprved prescribing infrmatin AND Medical recrd dcumentatin that Galafld will nt be used cncurrently with enzyme replacement therapy intended fr the treatment f Fabry disease, such as agalsidase beta (Fabrazyme). Quantity Limit: 14 capsules per 28 days Authrizatin Duratin: Initial apprval will be fr a duratin f six (6) mnths. Fr cntinuatin f cverage, medical recrd dcumentatin f clinical imprvement r lack f prgressin in signs and symptms f Fabry disease n six (6) mnths f migalastat is required. After the initial six (6) mnth apprval, subsequent apprvals fr cverage will be fr a duratin f ne (1) year. Reevaluatin f cverage will be every ne (1) year requiring medical recrd dcumentatin f clinical imprvement r lack f prgressin in signs and symptms f Fabry disease while n migalastat therapy. Nte: Examples f disease imprvement may include: Decreased symptms f Fabry disease (e.g., pain, hyphidrsis/anhidrsis, exercise intlerance, GI symptms, angikeratmas, abnrmal crnea, tinnitus/hearing lss) Imaging (brain/cardiac MRI, DEXA, renal ultrasund) Labratry testing (e.g., GL-3 in plasma/urine) r histlgical tests (e.g., renal bipsy)

15 TAKHZYRO (lanadelumab-fly) Review: Takhzyr (lanadelumab-fly) jins Cinryze and Haegarda as the third agent t be apprved fr prphylaxis against attacks caused by HAE. It ffers several advantages ver Cinryze and Haegarda: it is lnger-acting, allwing fr a dsing frequency f every 2 weeks. Additinally, Takhzyr prvides a different mechanism fr preventing bradykinin prductin: inhibitin f plasma kallikrein. Bradykinin is a ptent vasdilatr that increases vascular permeability resulting in swelling and pain assciated with HAE. Takhzyr is administered as a 300mg subcutaneus injectin, given nce every 2 weeks. Its efficacy was demnstrated in a randmized, placeb-cntrlled clinical trial in patients 12 years and lder with HAE. Patients in the study were allwed t cntinue use f rescue medicatin and were randmized t placeb, Takhzyr 150mg every 4 weeks, Takhzyr 300mg every 4 weeks, r Takhzyr 300mg every 2 weeks. All treatment arms prduced clinical and statistically significant reductins in HAE attack rate versus placeb. The mean reductin in attack rates was cnsistently greater fr patients treated with Takhzry regardless f baseline histry f prir lng-term prphylaxis, laryngeal attacks, r attack rate during run in perid. There are n black bx warnings r cntraindicatins t Takhzyr. The mst cmmn adverse reactins seen in studies were injectin site reactin, upper respiratry infectin, headache, rash, myalgia, dizziness, and diarrhea. Plasma derived C1-INH is currently the preferred lng-term prphylaxis fr preventin f HAE attacks, per the 2017 guidelines. Lanadelumab, the first kallikrein inhibitr, is nt included in these guidelines. Up T Date als des nt prvide any specific recmmendatins regarding lanadelumab s place in therapy. A Clinical Review including Clinical Infrmatin, Efficacy Evidence, Safety Evidence, and Other Cnsideratins and a Financial Review Based n Cst Analysis were presented. Clinical Discussin: Tricia Heitzman made a mtin t accept the recmmendatins as written. Kevin Szczecina secnded the mtin. Nne were ppsed. Financial Discussin: N cmments r questins. Kevin Szczecina made a mtin t accept the recmmendatins as written. Keith Hunsicker secnded the mtin. Nne were ppsed. Outcme: Takhzyr is a pharmacy benefit and shuld be added t the Geisinger GHP Family frmulary at the Brand Tier. The fllwing prir authrizatin criteria shuld apply: Medical recrd dcumentatin f age greater than r equal t 12 years AND Medical recrd dcumentatin that Takhzyr is prescribed by an allergist, immunlgist, hematlgist, r dermatlgist AND Medical recrd dcumentatin f a diagnsis f hereditary angiedema (HAE) established and supprted by dcumentatin f: Recurrent, self-limiting, nn-inflammatry subcutaneus angiedema withut urticaria which lasts mre than 12 hurs OR Laryngeal edema OR Recurrent, self-remitting abdminal pain which lasts mre than 6 hurs, withut clear rganic etilgy AND Medical recrd dcumentatin f specific abnrmalities in cmplement prteins, in the setting f a suggestive clinical histry r episdic angiedema withut urticaria; supprted by: Medical recrd dcumentatin f tw (2) r mre sets f cmplement studies, separated by ne mnth r mre, shwing cnsistent results f:

16 Lw C4 levels AND Less than 50% f the lwer limit f nrmal C1-INH antigenic prtein levels OR Less than 50% f the lwer limit f nrmal C1-INH functins levels AND Medical recrd dcumentatin f histry f mre than ne (1) severe event per mnth OR a histry f laryngeal attacks AND Medical recrd dcumentatin that Takhzyr is being used as prphylactic therapy fr hereditary angiedema (HAE) attacks AND Medical recrd dcumentatin f therapeutic failure n, intlerance t, r cntraindicatin t danazl Reauthrizatin inf: Initial apprval will be fr 6 mnths r less if the reviewing prvider feels it is medically apprpriate. Subsequent apprvals will be fr an additinal 12 mnths r less if the reviewing prvider feels it is medically apprpriate and will required medical recrd dcumentatin f cntinued disease imprvement r lack f disease prgressin. Takhzyr will n lnger be cvered if the member experiences unacceptable txicity r wrsening f disease Authrizatin Duratin: Initial apprval: 6 mnths, Reauthrizatin: 12 mnths Quantity Limit: 4ml per 28 days TALZENNA (talazparib) Review: Talzenna is indicated fr the treatment f adult patients with deleterius r suspected deleterius germline BRCA-mutated (gbrcam) HER2-negative lcally advanced r metastatic breast cancer. Select patients fr therapy based n an FDA-apprved cmpanin diagnstic fr Talzenna. Talzenna (talazparib) jins Lynparza (laparib) as the secnd FDA-apprved ply (ADP-ribse) plymerase (PARP) inhibitr t treat breast cancer. Lynparza is indicated in patients with deleterius r suspected deleterius gbrcam HER2-negative metastatic breast cancer wh have been treated with chemtherapy in the neadjuvant, adjuvant, r metastatic setting. Per NCCN, bth agents are recmmended as single agents (preferred regimen) fr recurrent r stage (IV) (M1) HER2-negative, BRCA 1/2- germline mutated disease with symptmatic visceral disease r visceral crisis and that is hrmne receptr-negative r hrmne receptr-psitive and endcrine therapy refractry. Talzenna is available as 0.25 mg and 1 mg ral capsules. The recmmended dsage is 1 mg taken as a single ral dse daily, with r withut fd. Fr patients with mderate renal impairment (CLcr ml/min) the recmmended dse is 0.75 mg daily. Talzenna was apprved based upn data frm the EMBRACA study, an pen-label clinical trial in 431 patients with gbrcam HER2-negative lcally advanced r metastatic breast cancer. Patients received Talzenna 1 mg r healthcare prvider s chice f chemtherapy (capecitabine, eribulin, gemcitabine, r vinrelbine) until disease prgressin r unacceptable txicity. Talzenna demnstrated a statistically significant imprvement in median PFS, with a median PFS f 8.6 mnths in the Talzenna arm cmpared t 5.6 mnths in the chemtherapy arm. Cnsistent PFS results were bserved acrss patient subgrups defined by study stratificatin factrs (line f therapy, triplenegative breast cancer status, and histry f CNS metastases). There are n cntraindicatins r black bx warnings assciated with the use f Talzenna. Like Lynparza, Talzenna has warnings and precautins fr myeldysplastic Syndrme/Acute Myelid Leukemia (MDS/AML) and embry-fetal txicity; Talzenna has an additinal warning fr myelsuppressin. Unlike Lynparza, the labeling fr Talzenna des nt cntain a warning fr pneumnitis. The mst cmmn adverse reactins reprted in clinical studies (incidence 20%) were fatigue, anemia, nausea, neutrpenia, headache, thrmbcytpenia, vmiting, alpecia, diarrhea, decreased appetite. The mst cmmn labratry abnrmalities (incidence 25%) were: Decreases in hemglbin, platelets, neutrphils, lymphcytes, leukcytes, and calcium. Increases in glucse, alanine