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.

Ryan Watts, Denali CEO

Bio­gen hands De­nali $1B-plus in cash, $1B-plus in mile­stones to part­ner on late-stage Parkin­son’s drug

Biogen is handing over more than a billion dollars cash to partner with the up-and-coming neurosciences crew at Denali on a new therapy for Parkinson’s. And the big biotech is ready to pile on more than a billion dollars more in milestones — if the alliance is a success.

For Biogen $BIIB, the move on Denali’s small molecule inhibitors of LRRK2 puts them in line to collaborate on a late-stage program for DNL151, which is scheduled to start next year.

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Michel Vounatsos, Biogen CEO (via YouTube)

UP­DAT­ED: Bio­gen scores a pri­or­i­ty re­view for its Alzheimer's drug ad­u­canum­ab, mov­ing one gi­ant leap for­ward in its con­tro­ver­sial quest

Biogen scored a big win at the FDA today as regulators accepted their application for the controversial Alzheimer’s drug aducanumab and gave it a priority review.

The PDUFA date is March 7, 2021.

Significantly, Biogen says it did not use its priority review voucher to win special treatment at the FDA. The agency handed that out gratis.

That’s the ideal scenario Biogen was looking for as disappointed analysts wondered aloud about the delayed application earlier in the year.

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Moncef Slaoui, Getty Images

When will it end? Big Phar­ma's top vac­cine ex­pert at OWS of­fers a speedy time­line for a Covid-19 vac­cine — ei­ther be­fore or right af­ter the elec­tion

Moncef Slaoui hasn’t started making plans for his summer vacation next year. But he offers high odds that all Americans will be able to do that in the not too distant future.

In an interview with a pair of sympathetic podcasters at the conservative American Enterprise Institute, Slaoui provides an education to listeners on how any drug or vaccine can be sped through trials. And he leaves the door wide open to the notion that the leading vaccine developers can demonstrate efficacy and safety in a compelling fashion as early as October — or as late as the end of this year.

Levi Garraway, Roche CMO (Source: Genentech)

UP­DAT­ED: FDA hands out a quick OK for po­ten­tial SMA block­buster ris­diplam, giv­ing Genen­tech and Roche a chance to chal­lenge ri­vals on the price

US regulators handed Roche and Genentech a big win Friday afternoon, one that has market-shaping potential for its high-priced rivals from Novartis and Biogen.

The FDA has green-lit the companies’ spinal muscular atrophy drug risdiplam, which will be marketed as Evrysdi in the US, for use in patients two months and older. It’s the first SMA drug that can be taken orally, as Biogen’s Spinraza is injected into the spine while Novartis’ Zolgensma is a gene therapy.

Per­cep­tive fields SPAC #3 as an­oth­er group of biotechs scoops up $364M in lat­est Nas­daq romp

There’s no sign that the windfall of cash dropping biotech’s way on Wall Street is abating. Three more biopharmas priced IPOs on Thursday and Friday morning, riding a historic boom with a $364 million payoff.

London-based biotech Freeline Therapeutics took home the lion’s share of the cash with $159 million after pricing 8,823,529 shares at $18 a pop. Checkmate Pharmaceuticals, of Cambridge, MA, raised $75 million with an offer of 5 million shares at $15 — right at the midpoint of its range. And Arya Sciences Acquisition Corp III, the third in a series from Perceptive, priced 13,000,000 shares at $10 per share.

Douglas Fambrough, Dicerna CEO (Boehringer Ingelheim via YouTube)

Roche-backed Dicer­na push­es in­to the pack rac­ing to­ward the block­buster hep B goal line, armed with PhI da­ta

Dicerna has lined up a set of proof-of-concept data from a small cohort of hepatitis B patients in a match-up against some heavyweight rivals which got out in front of this race. And right in the front row you’ll find a team from Roche, which paid $200 million in cash and offered another $1.5 billion in milestones to partner with Dicerna $DRNA on their RNAi program for hep B.

Right now it’s looking competitive, with lots of big challenges ahead.

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Jan Hatzius (Photographer: Christopher Goodney/Bloomberg via Getty Images)

When will it end? Gold­man econ­o­mist gives late-stage vac­cines a good shot at tar­get­ing 'large shares' of the US by mid-2021 — but the down­side is daunt­ing

It took decades for hepatitis B research to deliver a slate of late-stage candidates capable of reining the disease in.

With Covid-19, the same timeline has devoured all of 5 months. And the outcome will influence the lives of billions of people and a multitrillion-dollar world economy.

Count the economists at Goldman Sachs as optimistic that at least one of these leading vaccines will stay on this furiously accelerated pace and get over the regulatory goal line before the end of this year, with a shot at several more near-term OKs. That in turn should lead to the production of billions of doses of vaccines that can create herd immunity in the US by the middle of next year, with Europe following a few months later.

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J&J gets a fresh OK for es­ke­t­a­mine, but is it re­al­ly the game-chang­er for de­pres­sion Trump keeps tweet­ing about?

Backed by an enthusiastic set of tweets from President Trump and a landmark OK for depression, J&J scooped up a new approval from the FDA for Spravato today. But this latest advance will likely bring fresh scrutiny to a drug that’s spurred some serious questions about the data, as well as the price.

First, the approval.

Regulators stamped their OK on the use of Spravato — developed as esketamine, a nasal spray version of the party drug Special K or ketamine — for patients suffering from major depressive disorder with acute suicidal ideation or behavior.

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President Trump (AP Images)

UP­DAT­ED: FDA takes the lead on defin­ing es­sen­tial un­der Trump's 'Buy Amer­i­can' ex­ec­u­tive or­der — as phar­ma warns of sup­ply chain dis­rup­tion

President Donald Trump has signed an executive order detailing how the federal government should help on-shore drug manufacturing — and the FDA will play a central role.

The agency now has three months to draw up the list of “essential medicines, medical countermeasures, and their critical inputs” that the US must have available at all times. Various departments and agencies are then directed to buy these drugs and their ingredients from American manufacturers.