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.

Brian Kaspar. AveXis via Twitter

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But in his first public response, the scientific founder at AveXis — acquired by Novartis for $8.7 billion — is firing back. And he says that not only was he not involved in any wrongdoing, he’s ready to defend his name as needed.

I reached out to Brian Kaspar after Novartis put out word that he and his brother Allen had been axed in mid-May, two months after the company became aware of the allegations related to manipulated data. His response came back through his attorneys.

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Novartis CEO Vas Narasimhan [via Bloomberg/Getty]

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But he couldn’t quite get there.

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In one of the least anticipated moves of the year, the FDA has rejected Sarepta’s application for an accelerated approval of its Duchenne MD drug golodirsen after fretting over safety issues.

In a statement that arrived after the bell on Monday, Sarepta explained the CRL, saying:

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Roche raids Eli Lil­ly for its next chief med­ical of­fi­cer as San­dra Horn­ing plans to step down

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Af­ter a posse of Wall Street an­a­lysts pre­dict a like­ly new win for Sarep­ta, we're down to the wire on a crit­i­cal FDA de­ci­sion

As Bloomberg notes, most of the Wall Street analysts that cover Sarepta $SRPT are an upbeat bunch, ready to cheer on the team when it comes to their Duchenne MD drugs, or offer explanations when an odd setback occurs — as happened recently with a safety signal that was ‘erroneously’ reported last week.

Ritu Baral Cowen
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UP­DAT­ED: No­var­tis spin­off Nabri­va fi­nal­ly scores its first an­tibi­ot­ic ap­proval

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The drug, lefamulin, has been developed as an intravenous and oral formulation and been tested in two late-stage clinical trials. The semi-synthetic compound, whose dosing can be switched between the two formulations, is engineered to inhibit the synthesis of bacterial protein by binding to a part of the bacterial ribosome.

Saqib Islam. CheckRare via YouTube

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SpringWorks

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