FDA shoots down Mallinck­rodt's re­demp­tion at­tempt, spurns rare kid­ney dis­ease drug for a sec­ond time

What­ev­er hope Mallinck­rodt had fol­low­ing a nar­row rec­om­men­da­tion by the FDA ad­vi­so­ry com­mit­tee to ap­prove ter­li­pressin has been dashed by a firm re­jec­tion.

The com­plete re­sponse let­ter stabbed right through the UK drug­mak­er’s case for the drug, as reg­u­la­tors are ask­ing for “more in­for­ma­tion to sup­port a pos­i­tive risk-ben­e­fit pro­file for ter­li­pressin” as a treat­ment of the rare kid­ney dis­ease known as he­pa­tore­nal syn­drome type 1, or HRS-1.

This is the sec­ond time reg­u­la­tors are spurn­ing the drug, which got a fast track des­ig­na­tion in 2005 on­ly to be re­ject­ed in 2009. Soon af­ter­wards its orig­i­nal de­vel­op­er, Or­phan Ther­a­peu­tics, out-li­censed North Amer­i­can rights to Ikaria Ther­a­peu­tics, which Mallinck­rodt ac­quired in 2015.

Dis­ap­point­ed, Mallinck­rodt CSO Steven Ro­mano said his team stands by the da­ta from the Phase III CON­FIRM study, “the largest clin­i­cal tri­al ever con­duct­ed in this rare con­di­tion” in­volv­ing 300 pa­tients.

Steven Ro­mano

“HRS-1 is a com­plex dis­ease that af­fects a crit­i­cal­ly ill pa­tient pop­u­la­tion with no ap­proved treat­ment in the U.S. at present,” he added in a state­ment. “We are sur­prised by and dis­agree with the FDA’s de­ci­sion and re­main com­mit­ted to pur­su­ing all avail­able op­tions as we con­tin­ue work­ing with the FDA to­ward ap­proval of ter­li­pressin in or­der to help ad­dress this dif­fi­cult and life-threat­en­ing syn­drome.”

Just a year ago, Cowen an­a­lysts hailed the pos­i­tive da­ta as a “key suc­cess” for em­bat­tled Mallinck­rodt, which was fac­ing a litany of fail­ures for its ac­quired pipeline while un­der a cloud of opi­oid lit­i­ga­tion and law­suits tar­get­ing “ill-got­ten gains” from Ac­thar, its cash cow.

To­day the CRL counts as “yet an­oth­er set­back” in SVB Leerink an­a­lyst Ami Fa­dia’s eyes.

“We note that de­spite the over­all pos­i­tive vote, in our view the tone of the Ad­Com dis­cus­sion was de­cid­ed­ly cau­tious, strug­gling to bal­ance the high-un­met need with no cur­rent­ly avail­able treat­ment op­tions with con­cerns about lack of clin­i­cal ben­e­fit and an un­cer­tain risk mit­i­ga­tion plan,” she wrote.

On the ef­fi­ca­cy front, the FDA’s (and some of the out­side ex­perts’) chief con­cern was that the pri­ma­ry end­point — which ter­li­pressin met — was a sur­ro­gate end­point that mea­sures cre­a­ti­nine lev­els in blood. But it was un­clear whether that led to clin­i­cal im­prove­ments for HRS-1 pa­tients, who were char­ac­ter­ized by cir­rho­sis and could de­vel­op life-threat­en­ing kid­ney fail­ure with­in days.

More im­por­tant­ly, more pa­tients died in the drug arm than in the place­bo arm. And the FDA wasn’t sat­is­fied with the risk mit­i­ga­tion strat­e­gy that Mallinck­rodt of­fered. There was, how­ev­er, “no clear out­line on what would be con­sid­ered suf­fi­cient for ap­proval,” Fa­dia point­ed out.

Af­ter much de­lib­er­a­tion in Ju­ly, the Car­dio­vas­cu­lar and Re­nal Drugs Ad­vi­so­ry Com­mit­tee vot­ed 8-7 for ap­proval. Paul Rid­ker, a car­di­ol­o­gist at Brigham and Women’s Hos­pi­tal and one of the pan­elists, said he vot­ed yes but al­so wrote in “but bare­ly.”

Ap­proved in Eu­rope un­der the brand name Gly­pressin, ter­li­pressin now faces an un­cer­tain fu­ture in the US.

Mallinck­rodt, which has hint­ed at a po­ten­tial bank­rupt­cy fil­ing, didn’t spec­i­fy what the next steps will be. In­vestors sent the stock $MNK down 11.62%, edg­ing close to pen­ny-stock ter­ri­to­ry at $1.06.

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