Tri­fec­ta of sick­le cell dis­ease ther­a­pies ex­tend life ex­pectan­cy, but are not cost-ef­fec­tive — ICER

Dif­fer­ent ther­a­peu­tic traits bran­dished by the three ap­proved ther­a­pies for sick­le cell dis­ease all ex­tend life ex­pectan­cy, but their im­pact on qual­i­ty of life is un­cer­tain and their long-term cost-ef­fec­tive­ness is not up to scratch ac­cord­ing to the thresh­olds con­sid­ered rea­son­able by ICER, the non-prof­it con­clud­ed in a draft guid­ance re­port on Thurs­day.

Sick­le cell dis­ease (SCD), which en­com­pass­es a group of in­her­it­ed red blood cell dis­or­ders that typ­i­cal­ly af­flict those of African an­ces­try, im­pacts he­mo­glo­bin — and is char­ac­ter­ized by episodes of sear­ing pain as well as or­gan dam­age.

In re­cent years — three ther­a­pies have won FDA ap­proval. The first — ap­proved in 2017 to re­duce the se­vere com­pli­ca­tions that come with SCD — is Em­maus’ En­dari, which is a pu­ri­fied (phar­ma­ceu­ti­cal grade) ver­sion of the amino acid L-glu­t­a­mine.

Late last year two oth­er ther­a­pies re­ceived FDA ap­provals in quick suc­ces­sion. No­var­tis’ crizan­l­izum­ab, brand­ed Adakveo, was giv­en the FDA nod for its abil­i­ty to pre­vent va­so-oc­clu­sive crises (VOCs) —pe­ri­od­ic episodes of de­bil­i­tat­ing pain that oc­cur when sick­le-shaped red blood cells get stuck in­side blood ves­sels and de­prive the body of oxy­gen-rich blood. Soon af­ter, Glob­al Blood Ther­a­peu­tics’ vox­elo­tor, chris­tened Oxbry­ta, was ap­proved on the ba­sis of da­ta that showed it in­creased he­mo­glo­bin lev­els, al­though its use was not as­so­ci­at­ed with few­er pain crises.

Al­though a de­cline in acute pain crises and an in­crease in he­mo­glo­bin will help SCD pa­tients, there are oth­er acute and chron­ic con­di­tions that are cur­rent­ly not ad­dressed with these ther­a­pies that have a sig­nif­i­cant im­pact on qual­i­ty of life, re­searchers wrote in the draft re­port.

One of the ways ICER — an in­creas­ing­ly in­flu­en­tial, pri­vate­ly-held, cost-ef­fec­tive­ness watch­dog in the Unit­ed States — makes its long-term cost-ef­fec­tive­ness cal­cu­la­tions is us­ing qual­i­ty-ad­just­ed-life-years or QALYs.

QALYs mea­sure the state of health of a per­son or group in which the ben­e­fits — in terms of length of life — are ad­just­ed to re­flect the qual­i­ty of life. Re­cent­ly, ICER al­so in­cor­po­rat­ed the use of Equal Val­ue of Life Years Gained (evLYG) in its cal­cu­la­tions. The tool is de­signed to even­ly mea­sures any gains in length of life, re­gard­less of the treat­ment’s abil­i­ty to im­prove qual­i­ty of life.

Al­though ICER made sev­er­al as­sump­tions over the im­pact of these SCD treat­ments on acute or chron­ic com­pli­ca­tions as­so­ci­at­ed with the dis­ease, there re­mains a large dif­fer­ence in the cost per QALY and evLYG, ICER said.

“For ex­am­ple, cost per evLYG ranged from ap­prox­i­mate­ly $520,000 for crizan­l­izum­ab to $847,000 for L-glu­t­a­mine. Sce­nario analy­ses sug­gest treat­ment is most cost-ef­fec­tive for pa­tients with high­er rates of acute pain crises. Pa­tients who ex­pe­ri­ence 10 acute pain crises per year may have a cost per QALY as low as $615,000 with crizan­l­izum­ab.”

The list prices for the three treat­ments were the main dri­ver of the cost-ef­fec­tive­ness re­sults, with av­er­age an­nu­al costs of $88,000 for crizan­l­izum­ab, $84,000 for vox­elo­tor and $24,000 for L-glu­t­a­mine, ICER not­ed.

Com­bined with rel­a­tive­ly small im­prove­ments in QALYs gained — 0.85 for crizan­l­izum­ab, 0.96 for vox­elo­tor, and 0.10 for L-glu­t­a­mine — all in­cre­men­tal cost-ef­fec­tive­ness ra­tios were es­ti­mat­ed to be over $1 mil­lion per QALY, ICER cal­cu­lat­ed, high­light­ing that none of the analy­ses un­der­tak­en low­ered the es­ti­mat­ed cost per QALY to less than the bench­mark price of $150,000 per QALY.

“We be­lieve that ICER’s re­view is flawed, pre­ma­ture and risks ad­verse­ly im­pact­ing ac­cess to new, po­ten­tial­ly trans­for­ma­tive ther­a­pies for SCD,” a spokesper­son for Glob­al Blood Ther­a­peu­tics told End­points News. “The re­view runs counter to the FDA’s in­tent to pro­vide ear­li­er ac­cess to safe and ef­fec­tive treat­ments of se­ri­ous con­di­tions with high un­met need through ac­cel­er­at­ed ap­proval.”

A No­var­tis spokesper­son said that the Swiss drug­mak­er agrees with ICER’s clin­i­cal ef­fec­tive­ness as­sess­ment, but dis­agrees with oth­er as­pects of the re­port, with­out go­ing in­to de­tails.

“Over­all, sick­le cell dis­ease and VOCs are as­so­ci­at­ed with de­creased qual­i­ty of life – in­clud­ing cog­ni­tive and so­cial as­pects, as well as im­pact on em­ploy­ment and ed­u­ca­tion for pa­tients and care­givers. Many of these ef­fects can be hard to cap­ture with eco­nom­ic mod­els in sick­le cell dis­ease, a crit­i­cal point that ICER ac­knowl­edges.”

End­points has al­so con­tact­ed Em­maus for com­ment.

A fi­nal re­port, in­cor­po­rat­ing feed­back from the com­pa­nies, pa­tients and providers and an in­de­pen­dent pan­el of stake­hold­ers, is ex­pect­ed to be pub­lished by ICER in April.

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