J&J's Xarel­to, Amar­in's Vas­cepa are cost-ef­fec­tive, not bud­get friend­ly — ICER

ICER, an in­creas­ing­ly in­flu­en­tial cost-ef­fec­tive­ness watch­dog in the Unit­ed States, has con­clud­ed in its re­view of treat­ments for car­dio­vas­cu­lar dis­ease that while the cost of J&J’s Xarel­to and Amarin’s Vas­cepa meet its bench­mark for val­ue pric­ing — the two treat­ments will not like­ly treat as many pa­tients as hoped with­out sur­pass­ing the an­nu­al bud­get thresh­old cal­cu­lat­ed by ICER for each ther­a­py.

J&J’s Xarel­to, known chem­i­cal­ly as ri­varox­a­ban, is a blood thin­ner that was orig­i­nal­ly ap­proved to pre­vent deep vein throm­bo­sis in pa­tients un­der­go­ing ma­jor or­tho­pe­dic surgery and is wide­ly used in the man­age­ment of atri­al fib­ril­la­tion and ve­nous throm­boem­bol­ic dis­ease. Last year, it was cleared for use in com­bi­na­tion with as­pirin as a treat­ment to re­duce the risk of ma­jor car­dio­vas­cu­lar (CV) events in pa­tients with chron­ic coro­nary or pe­riph­er­al ar­te­r­i­al dis­ease — on the ba­sis of the piv­otal COM­PASS tri­al that in­di­cat­ed that the com­bi­na­tion spurred a 24% re­duc­tion of the risk of ma­jor CV events in the pa­tient pop­u­la­tion.

Amarin’s Vas­cepa, known chem­i­cal­ly as icos­apent eth­yl, is an omega-3 fat­ty acid de­rived from fish oil that was orig­i­nal­ly en­dorsed by the US reg­u­la­tor as a treat­ment for el­e­vat­ed triglyc­erides. How­ev­er, it is now un­der FDA re­view for an ex­pand­ed la­bel af­ter a land­mark tri­al — RE­DUCE-IT — showed the pill trig­gered a 25% re­duc­tion in the risk for the first oc­cur­rence of a ma­jor car­dio event, and a 26% re­duc­tion for 3-point MACE, a com­pos­ite of car­dio­vas­cu­lar death, non­fa­tal heart at­tack and non­fa­tal stroke. The reg­u­la­tor is set to make its de­ci­sion by De­cem­ber.

At cur­rent prices, both drugs fall with­in the val­ue-based price bench­mark range set by ICER:

Source: ICER, 2019

Click on the im­age to see the full-sized ver­sion

Xarel­to’s an­nu­al list price of $5,457 falls with­in ICER’s val­ue-based price bench­mark range of $5,200-$7,600 per year — in fact, the drug’s es­ti­mat­ed net price of $2,215 per year is sig­nif­i­cant­ly low­er than the ICER bench­mark. Clin­i­cal ex­perts at ICER’s pub­lic meet­ing sug­gest­ed they would con­sid­er us­ing the drug in ap­prox­i­mate­ly 30% of el­i­gi­ble pa­tients — but at the cur­rent price — on­ly rough­ly 6% of el­i­gi­ble pa­tients could be treat­ed in a giv­en year with­out cross­ing the po­ten­tial ICER thresh­old of $819 mil­lion an­nu­al­ly. Last year, Xarel­to gen­er­at­ed near­ly $2.5 bil­lion in glob­al sales.

In the case of Vas­cepa, the drug’s an­nu­al list price of $3,699 and es­ti­mat­ed net price of $1,625 are both sig­nif­i­cant­ly low­er than ICER’s val­ue-based price bench­mark range of $6,300-$9,200 per year. Ex­perts at ICER’s pub­lic meet­ing sug­gest­ed they would like to pre­scribe the drug, if ap­proved for the new in­di­ca­tion, to the ma­jor­i­ty of el­i­gi­ble pa­tients — but on­ly about 4% of el­i­gi­ble pa­tients could be treat­ed in a giv­en year with­out cross­ing the ICER thresh­old of $819 mil­lion an­nu­al­ly. In 2018, Vas­cepa gen­er­at­ed rough­ly $229 mil­lion in sales.

ICER’s bud­get thresh­old is based on cal­cu­la­tions that sug­gest that the US health care sys­tem, in the short term, may not be equipped to ab­sorb the ther­a­pies’ ex­pect­ed adop­tion if costs ex­ceed $819 mil­lion per drug, per year — with­out sidelin­ing oth­er drugs/ser­vices or con­tribut­ing to a rapid uptick in in­sur­ance costs.

In terms of long-term ef­fec­tive­ness, ICER found that both ther­a­pies pro­vid­ed gains in over­all sur­vival above and be­yond the cur­rent ar­se­nal of car­dio­vas­cu­lar ther­a­pies. How­ev­er, re­view­ers did high­light some sources of un­cer­tain­ty.

Al­though treat­ment with Xarel­to low­ered the risk of CV events, there was a surge in bleed­ing, re­view­ers not­ed. For Vas­cepa, it is un­clear whether the ther­a­py would be ef­fec­tive in pa­tients not treat­ed with statins — and the min­er­al oil place­bo used in the RE­DUCE-IT tri­al may not have been bi­o­log­i­cal­ly in­ert, they said. In ad­di­tion, al­though the RE­DUCE-IT tri­al test­ed a high­er dose of Vas­cepa, pri­or neg­a­tive re­sults test­ing dif­fer­ent for­mu­la­tions of omega-3 fat­ty acid de­rived from fish oil “have led some to wor­ry that these new re­sults could be wrong by chance.”

“(D)es­pite the re­port’s pos­i­tive con­clu­sion that Vas­cepa is cost-ef­fec­tive, we be­lieve that it un­der­states the true val­ue of Vas­cepa,” Amarin’s chief med­ical of­fi­cer Craig Gra­nowitz said in a state­ment on Thurs­day.

“For ex­am­ple, the re­port’s base-case analy­ses re­flect on­ly the costs of heart at­tack, stroke and car­dio­vas­cu­lar death and ex­clude oth­er high costs as­so­ci­at­ed with oth­er car­dio­vas­cu­lar events demon­strat­ed to be low­ered by Vas­cepa in the RE­DUCE-IT car­dio­vas­cu­lar out­comes study (e.g., revas­cu­lar­iza­tion pro­ce­dures and hos­pi­tal­iza­tion for un­sta­ble angi­na) as well as low­er rates of re­cur­ring car­dio­vas­cu­lar events in pa­tients treat­ed with Vas­cepa dur­ing the study.”

J&J said it had ex­pect­ed ICER to find Xarel­to cost-ef­fec­tive in its new in­di­ca­tion.

“How­ev­er, we do not en­dorse the use of cost-per-QALY or cost-per-life-year-gained analy­sis as the sole or pri­ma­ry ba­sis of de­ci­sion mak­ing,” the com­pa­ny said in a state­ment to End­points News.  

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