Dimethyl fumarate (Tecfidera ) Drug Formulary Review and Multiple Sclerosis Class Review

Transcription

1 Oregn Regin Pharmacy and Therapeutic Cmmittee (ORPTC) August 9, 2013 Key Decisins in Acute Care Dimethyl fumarate (Tecfidera ) Drug Frmulary Review and Multiple Sclersis Class Review With the recent release f dimethyl fumarate (Tecfidera ), an ral agent with minimal side effects was added t the agents fr treatment f multiple sclersis (MS). Cnsidering that this agent may have a significant impact n the treatment f MS, a review f the MS agent class was dne.. Direct and indirect cmparisn trials were reviewed. The beta interferns (Avnex, Rebif, Betasern, Extavia ) were cnsidered t be equivalent in safety and efficacy t each ther, t glatiramer (Cpaxne ) and t teriflunmide (Aubagi ). Currently, Aubagi lacks any lng term efficacy r safety data. Finglimd (Gilenya ) and natalizumab (Tysabri ) are tw f the mre effective agents; hwever cardivascular txicity and prgressive multifcal leukencephalpathy (PML) limit their use as primary agents. Data frm the trials published t date demnstrate that Tecfidera is at least as efficacius as the first line agents, the beta interferns (Avnex, Rebif, Betasern and Extavia ) and glatiramer (Cpaxne ) and suggests that it is mre efficacius. Lng-term experience limits this cnclusin. As an ral agent, it prvides an alternative fr patients with intlerance t injectins r infusins. The key trial DEFINE, fr Tecfidera, was a phase 3, randmized, placeb cntrlled trial that was cnducted at varius investigatinal sites in several cuntries. Patients were randmized t the active agent given twice daily r three times daily, r t placeb. Results demnstrated that dimethyl fumarate significantly reduced the risk f relapse and significantly reduced the risk f disability prgressin in patients with Relapsing- Remitting MS (RRMS) at tw years versus placeb. The mst cmmn adverse effects identified s far relate t flushing and gastrintestinal issues, which are less severe than many f the adverse events seen with ther agents in the MS class. Dimethyl fumarate is ne f the three ral agents apprved fr this chrnic cnditin. It has greater r equal efficacy t Aubagi and seems t be in line with Gilenya and Tysabri with regards t efficacy. Issues identified Due t side effect issues, there is limited infrmatin regarding cmbinatin therapy.

2 Pharmacy and Therapeutics Decisin Acute Care: Tecfidera and ther agents will nt be n preference lists. Patient wn meds will be used, if patients are admitted. Ambulatry Clinics: Tysabri n frmulary Health Plan: Frmulary with n restrictin: Avnex, Rebif, Tecfidera, Cpaxne Medical benefit with criteria fr usetysabri Nn-frmulary with criteria fr use(prir authrizatin): Betasern, Extavia, Gilenya, and Aubagi Sertnin Agnists (Triptans) Class Review Currently there are fur generic triptans nw n the market: sumatriptan (Imitrex ), naratriptan (Amerge ), rizatriptan (Maxalt ), and zlmitriptan (Zmig ). Fur brand name triptans are als available: almtriptan (Axert ), frvatriptan (Frva ), eletriptan (Relpax ) and zlmitriptan nasal (Zmig ). All f these agents are available as ral tablets. Sumatriptan is the nly triptan available as injectable prduct. Sumatriptan and Zmig are tw triptans that can be administered via nasal spray. The efficacy f the triptans has been measured using a variety f different utcmes which makes cmparing individual cmparatr trials mre difficult. In general, headache relief within tw hurs f medicatin administratin, recurrence f headache within 24 hurs, and the need fr an alternative rescue medicatin are parameters that have been cnsistently studied. Sumatriptan is the gld standard t which ther triptans have been cmpared, primarily because it has the lngest clinical experience and the widest range f frmulatins. In a meta-analysis review, the triptans appear t be equally as effective with eletriptan slightly better fr initial 2 hur relief. Rizatriptan, eletriptan, and almtriptan all appear t ffer better sustained pain-free intervals ver the ther agents. Naratriptan and almtriptan demnstrated better patient tlerability; hwever, naratriptan was nt as effective in the ther utcmes that were measured. In a review f the cmparatr trials, the differences amng the triptans are relatively small but may be clinically relevant fr individual patients. In the clinical trials, there were n cnsistent differences between triptans in the rate f verall adverse events. All triptans are cntraindicated in the presence f cardivascular disease. The safety f treating mre than fur headaches per mnth has nt been established. Therefre, the Eurpean Federatin f Neurlgic Sciences have established headache veruse criteria. Overuse was qualified as having a headache n mre than fifteen days per mnth and the use f triptans n mre than ten days per mnth fr three mnths. Lcal experts stated that sumatriptan is the drug f chice in the triptan class. Having available ther agents as ptins prvide flexibility fr the treatment f individual patients needs.

3 Issues identified N issues identified Pharmacy and Therapeutics Decisin Acute Care: A therapeutic interchange fr triptans will be develped if it is financially reasnable t d s. This prject is being addressed at the system level thrugh the Pharmacy Frmulary Wrkgrup. At this time, there is n change recmmended t the current status: The fur generic prducts (naratriptan, rizatriptan, sumatriptan, and zlmitriptan) are n frmulary. The brand name prducts (Axert, Frva, Relpax and Zmig nasal spray) are nn-frmulary. Ambulatry Clinics: On preference list: all fur generic prducts (naratriptan, rizatriptan, sumatriptan and zlmitriptan). Nt n preference list: the brand-name tablets Axert, Frva and Relpax and Zmig nasal spray. Health Plan: Criteria fr use have been develped fr brand name prducts because all triptans have been added t the state wide Individual and Small Grup Frmulary. Fr this frmulary, the quantity limits fr the brand name prducts will be defined as fllws: Almtriptan (Axert ) tablets: 12 tablets/30 days Eletriptan (Relpax ) tablets: 12 tablets/30 days Frvatriptan (Frva ) tablets: 9 tablets/30 days Zlmitrptan (Zmig ) nasal spray: 6 single use nasal spray units (package size = 6 sprays) All brand name triptan prducts are Nn-Frmulary fr OHP/Cmmercial/Medicare lines f business and clinical criteria fr use will include the trial and failure f tw generic triptan medicatins Algliptin (Nesina ) and Algliptin cmbinatin Frmulary Review A new dipeptidyl peptidase-4 inhibitr (DPP-4), algliptin (Nesina ) and tw cmbinatin agents [Oseni (algliptin/piglitazne) and Kazan (algliptin/metfrmin)] were recently marketed. The DPP-4 inhibitrs are taken as mntherapy r as cmbinatin prducts t treat diabetes, and have similar efficacy t ne anther, with an average HbA1c reductin f %

4 depending n the agent. Algliptin demnstrated efficacy in lwering bld glucse levels frm 0.5 t 0.9% in seven clinical trials. The cmbinatin prducts, Kazan and Oseni, prvide additive, but nt synergistic lwering f the HbA1c. There have been n clinical studies cnducted that evaluate the efficacy f the cmbinatin DPP-4 inhibitr agents (i.e., Kazan, Oseni, Jentaduet, Janumet, Janumet XR, Kmbiglyze XR ), hwever, the biequivalence f these agents has been demnstrated and the efficacy f the cmbinatin f the individual agents has als been demnstrated in clinical studies. One benefit f DPP-4 inhibitrs ver ther antihyperglycemic agents is lw t n risk f hypglycemia r weight gain when used alne. Because these agents have lw efficacy, the individual DPP-4 medicatins are usually given in cmbinatin with ther prducts. Adverse events assciated with the different DPP-4 agents are relatively similar. Cmmnly reprted events include diarrhea, nausea, naspharyngitis and upper respiratry infectin. Seriusly reprted adverse events include pancreatitis and angiedema. Hypglycemia risk was elevated when these agents were cmbined with sulfnylureas r insulin. There have been pst-marketing reprts f fatal and nn-fatal hepatic failure in patients taking the newest agent, algliptin, althugh sme f the reprts cntain insufficient infrmatin necessary t establish prbable cause. Hepatic enzyme elevatins have been reprted with ther DPP-4 agents but nt at this level f injury. Guidelines place the DPP-4 inhibitr agents alng with sulfnylureas, thiazlidinedines (e.g., piglitazne), GLP-1 receptr agnists, and basal insulin at the secnd level after first line metfrmin therapy. Fr mst patients, a sulfnylurea medicatin is a reasnable secnd line agent, given the relative efficacy, tlerability, lng term experience/safety prfile and very lw cst ver newer agents such as the DPP-4 Inhibitrs and GLP-1 agnists. Sulfnylureas d carry an increased risk fr hypglycemia that ranges in intensity; very few events are clinically significant (fasting plasma glucse f less than mg/dl with r withut symptms) and few require medical assistance. There is abut a 30% increased rate f reprted hypglycemia with sulfnylureas versus DPP-4 inhibitrs in cmparative trials, hwever, few incidents were reprted as clinically significant. There were n fatalities reprted in these trials secndary t hypglycemic events. Glipizide r glimepiride are recmmended ver lnger acting sulfnylureas (glyburide r chlrprpamide) t reduce risk f hypglycemic events. This is especially imprtant in lder patients that have an increased risk fr prlnged hypglycemia. Piglitazne is a reasnable alternative fr certain patients when hypglycemia is experienced with sulfnylureas in spite f dse adjustments. Piglitazne, nw available as a lw cst generic, is mre effective than DPP-4 inhibitrs, but must be used selectively (e.g., there are cautins against use in certain heart failure patients and thse with histry r active bladder cancer).. Issues: N infrmatin abut use f the newer medicatins in the pediatric ppulatin hwever there is n restrictin fr this grup in the clinical plicy.

5 Experts were in supprt f recmmendatins RECOMMENDATIONS fr Nesina, Kazan and Oseni : Acute Care: Nn-frmulary, due t Therapeutic Interchange Ambulatry Clinics: Nt n preference list Health Plan: Frmulary with criteria fr use RECOMMENDATIONS fr Changes in the Clinical Criteria fr Use all medicatins in this class: Acute Care: Recmmend adding algliptin t the DPP-4 Inhibitr Therapeutic Interchange plicy T be taken as a recmmendatin t the System Frmulary Wrkgrup fr apprval and build in Epic. Ambulatry Clinics: N change in this class Health Plan: The clinical criteria fr use fr all DPP-4 agents (in additin t the GLP-1 agents) shall be changed t allw use f sulfnylurea OR piglitazne