Mallinck­rodt's woes per­sist as re­for­mu­lat­ed opi­oid painkiller fails to pass FDA muster

The FDA’s re­luc­tance with pre­scrip­tion painkillers at a time the Unit­ed States is swept by a tsuna­mi of opi­oid abuse, over­dose and ad­dic­tion was on full dis­play on Wednes­day, when the reg­u­la­tor re­ject­ed Mallinck­rodt’s $MNK abuse-de­ter­rent opi­oid painkiller, so­lic­it­ing more da­ta from the UK drug­mak­er.

The drug un­der scruti­ny was a tweaked ver­sion of Rox­i­codone, an im­me­di­ate-re­lease for­mu­la­tion of the com­mon­ly abused opi­oid oxy­codone that was ap­proved by the FDA in 2000. This re­for­mu­la­tion was de­signed to de­ter abuse via snort­ing or in­ject­ing. In its CRL, the agency “pro­vid­ed guid­ance re­gard­ing ar­eas of fur­ther eval­u­a­tion nec­es­sary to re­sub­mit the NDA for fur­ther re­view,” Mallinck­rodt said.

Shares of the Staines-up­on-Thames-based com­pa­ny, which said it would spin off its spe­cial­ty busi­ness last week, were down about 9% pre-mar­ket. The an­nounce­ment fol­lows an­oth­er set­back: one of two late-stage drugs Mallinck­rodt won as part of its $1.2 bil­lion ac­qui­si­tion of Su­cam­po failed a piv­otal study in No­vem­ber.

The CRL for the painkiller does not come as a com­plete sur­prise. In a re­view last month, FDA staff point­ed out that the agency had not made any de­fin­i­tive con­clu­sions re­gard­ing whether the drug could be ma­nip­u­lat­ed for in­tra­venous abuse, as Mallinck­rodt had not yet sub­mit­ted da­ta from sev­er­al key stud­ies as part of its NDA. A pan­el of in­de­pen­dent ex­perts re­view­ing the drug a few days lat­er con­curred, sug­gest­ing the drug be la­beled as an abuse de­ter­rent on­ly via the nasal route.

This could cul­mi­nate in a sim­i­lar sit­u­a­tion to that of En­do’s $ENDP Opana, which was with­drawn from the mar­ket last year at the be­hest of the FDA, af­ter post-mar­ket da­ta showed the re­for­mu­lat­ed opi­oid painkiller was be­ing abused in­tra­venous­ly at a high­er rate, even as rates of nasal abuse fell.

But Mallinck­rodt is plan­ning to plough ahead. The com­pa­ny in­tends to re­quest a meet­ing in the com­ing weeks with the reg­u­la­tor to dis­cuss its next steps, it said on Wednes­day.

On av­er­age, opi­oid over­dos­es kill 115 Amer­i­cans per day, and the eco­nom­ic bur­den of pre­scrip­tion opi­oid mis­use alone is a hefty $78.5 bil­lion each year, in­clud­ing the health­care costs, lost pro­duc­tiv­i­ty, and crim­i­nal jus­tice in­volve­ment, ac­cord­ing to the CDC. As the num­ber of opi­oid-re­lat­ed deaths mount, the FDA has large­ly changed its tune on the oft’ mis­used class of drugs by amend­ing its pre­scrib­ing rec­om­men­da­tions,track­ing the num­ber of pre­scrip­tions, tight­en­ing scruti­ny and re­quir­ing man­u­fac­tur­ers to de­vel­op abuse-de­ter­rent for­mu­la­tions.

How­ev­er, the agency is not quite im­pos­ing a blan­ket ban on all things opi­oid. Last month, it ap­proved Acel­Rx Phar­ma­ceu­ti­cals $ACRX painkiller Dsu­via, a drug 10-times more po­tent than fen­tanyl, which in turn is a syn­thet­ic opi­oid pain re­liev­er that is 50 to 100 times more po­tent than mor­phine. The con­tro­ver­sial ap­proval was sanc­tioned de­spite height­en­ing con­cern and fiery crit­i­cism (from a host of crit­ics in­clud­ing a hand­ful of US sen­a­tors) on the grounds that the drug — which was de­vel­oped in col­lab­o­ra­tion with the De­part­ment of De­fense — is a sub­lin­gual for­mu­la­tion, mak­ing it ide­al for mil­i­tary use, not­ed FDA Com­mis­sion­er Scott Got­tlieb.

John Hood [file photo]

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