Ail­ing Mallinck­rodt's drug for rare, life-threat­en­ing re­nal con­di­tion clears piv­otal study

Em­bat­tled Mallinck­rodt — tar­nished by a cloud of opi­oid lit­i­ga­tion as well as its con­tro­ver­sial­ly ex­pen­sive Ac­thar gel — will en­joy its sliv­er of op­ti­mism that comes with a pos­i­tive piv­otal tri­al.

The UK drug­mak­er on Thurs­day un­veiled da­ta from a late-stage tri­al test­ing the drug, ter­li­pressin, in pa­tients with a life-threat­en­ing, pro­gres­sive rare com­pli­ca­tion of liv­er dis­ease that trig­gers kid­ney fail­ure called he­pa­tore­nal syn­drome type 1 (HRS-1), which af­fects an es­ti­mat­ed 30,000 to 40,000 in the Unit­ed States each year, the com­pa­ny said, adding that pa­tients face a poor prog­no­sis, with a me­di­an sur­vival time of less than two weeks and more than 80% mor­tal­i­ty with­in three months.

Pa­tients with HRS ex­pe­ri­ence a con­stric­tion of the blood ves­sels that feed the kid­neys, which leads to de­creased blood flow to the or­gans, even­tu­al­ly im­pair­ing their func­tion. The on­ly cu­ra­tive ther­a­py for pa­tients is a liv­er trans­plant, which is in­tend­ed to al­so fix the as­so­ci­at­ed im­paired kid­ney func­tion — but the pro­ce­dure does not guar­an­tee that, and some pa­tients per­ma­nent­ly re­quire dial­y­sis, or worse, a kid­ney trans­plant. In ad­di­tion, lim­it­ed donors and long wait­ing lists make the trans­plant op­tion not the most fea­si­ble al­ter­na­tive.

Ter­li­pressin is en­gi­neered to ac­ti­vate va­so­pressin (al­so called an­tid­i­uret­ic hor­mone) and is com­mon­ly used in dif­fer­ent in­di­ca­tions, par­tic­u­lar­ly in pa­tients with end-stage liv­er dis­ease. The com­pound is cur­rent­ly ap­proved in Eu­rope for he­pa­tore­nal syn­drome as well as bleed­ing esophageal varices, un­der the brand name Gly­pressin, and is man­u­fac­tured by Swiss spe­cial­ty phar­ma­ceu­ti­cal drug­mak­er Fer­ring Phar­ma­ceu­ti­cals.

Mallinck­rodt’s $MNK CON­FIRM tri­al test­ed the com­pound in 300 pa­tients, and the study met the main goal of ver­i­fied HRS-1 re­ver­sal (p=0.012) — an end­point that con­sti­tutes three com­po­nents: re­nal func­tion im­prove­ment, avoid­ance of dial­y­sis and short-term sur­vival.

De­tailed da­ta will be pre­sent­ed at a med­ical con­fer­ence, the com­pa­ny said, adding that it plans to sub­mit a US mar­ket­ing ap­pli­ca­tion ear­ly next year.

“(T)his is a key suc­cess for its ac­quired pipeline when up un­til to­day, sev­er­al as­sets in­clud­ing stannso­porfin (dis­con­tin­ued), VTS-270 (failed Phase 3, but still in dis­cus­sions with FDA) and CPP-1X/sulin­dac (dis­con­tin­ued) all failed to hit the mark,” Cowen an­a­lysts wrote in a note.

Apart from ter­li­pressin, Mallinck­rodt is al­so ex­pect­ing late-stage da­ta on its skin graft strat­a­graft in the com­ing months.

“Man­age­ment has pegged the peak glob­al op­por­tu­ni­ty at >$300M, and not­ed that along with Strat­a­graft this could more than off­set the loss-of-ex­clu­siv­i­ty (LOE) im­pact from Ofirmev in the out­er years,” the an­a­lysts added.

As part of its sec­ond-quar­ter re­sults ear­li­er this month, Mallinck­rodt dis­closed that it had sus­pend­ed plans to spin off its spe­cial­ty gener­ics busi­ness, cit­ing “cur­rent mar­ket con­di­tions and de­vel­op­ments, in­clud­ing in­creas­ing un­cer­tain­ties cre­at­ed by the opi­oid lit­i­ga­tion.” It al­so said it ex­pects Ac­thar sales to gen­er­ate less than $1 bil­lion in 2019 sales, cit­ing on­go­ing un­cer­tain­ty.

Apart from its pur­port­ed in­volve­ment in the opi­oid cri­sis, the Staines-up­on-Thames-based com­pa­ny has long elicit­ed the ire of reg­u­la­to­ry agen­cies and the in­dus­try re­lat­ed to Ac­thar, which is man­u­fac­tured via ex­trac­tion from the pi­tu­itary glands of slaugh­tered pigs —es­sen­tial­ly the same way as it was when it was first dis­cov­ered in the late 1940s.

How­ev­er, the drug’s price has cat­a­pult­ed from $40 per vial in 2001 to a whop­ping $38,892. In a law­suit filed ear­li­er this month, health in­sur­er Hu­mana said it was seek­ing to re­coup from Mallinck­rodt “ill-got­ten” gains.

The Fed­er­al Trade Com­mis­sion — along with the states of Alas­ka, Mary­land, New York, Texas and Wash­ing­ton — al­leged Mallinck­rodt had tak­en ad­van­tage of its mo­nop­oly to re­peat­ed­ly raise the price of Ac­thar and ac­quired the rights to its great­est com­pet­i­tive threat to keep com­pe­ti­tion at bay, the com­pa­ny agreed in 2017 to part with $100 mil­lion to set­tle those charges. This June, the US De­part­ment of Jus­tice joined two whistle­blow­er law­suits in al­leg­ing that the com­pa­ny used a foun­da­tion as a con­duit to pay il­le­gal kick­backs in the form of co­pay sub­si­dies for Ac­thar so it could mar­ket the drug as “free” to doc­tors and pa­tients while in­creas­ing its price be­tween 2010 and 2014.

Health­care Dis­par­i­ties and Sick­le Cell Dis­ease

In the complicated U.S. healthcare system, navigating a serious illness such as cancer or heart disease can be remarkably challenging for patients and caregivers. When that illness is classified as a rare disease, those challenges can become even more acute. And when that rare disease occurs in a population that experiences health disparities, such as people with sickle cell disease (SCD) who are primarily Black and Latino, challenges can become almost insurmountable.

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David Meek, new Mirati CEO (Marlene Awaad/Bloomberg via Getty Images)

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