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.

Take­da swoops in to buy lit­tle biotech part­ner and its celi­ac drug poised to 'change stan­dard of care'

Having spent three years carefully grooming PvP Biologics and its drug for celiac disease, Takeda is happy enough with the proof-of-concept data to buy it all.

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Grow­ing ac­cep­tance of ac­cel­er­at­ed path­ways for nov­el treat­ments: but does reg­u­la­to­ry ap­proval lead to com­mer­cial suc­cess?

By Mwango Kashoki, MD, MPH, Vice President-Technical, and Richard Macaulay, Senior Director, of Parexel Regulatory & Access

In recent years, we’ve seen a significant uptake in the use of regulatory options by companies looking to accelerate the journey of life-saving drugs to market. In 2018, 73% of the novel drugs approved by the U.S. Federal Drug Administration (FDA) were designated under one or more expedited development program categories (Fast Track, Breakthrough Therapy, Priority Review, and Accelerated Approval).ᶦ

Mi­cro­bio­me Q&A: New study maps the vagi­na's 'op­ti­mal mi­cro­bio­ta' — and its im­pli­ca­tions for bio­phar­ma

The widely-held notion that the “optimal” vaginal microbiota is dominated by one strain of lactic-acid producing bacteria has now been challenged in a new paper, published in Nature Communications on Wednesday, which used advanced gene sequencing methods to map out the most comprehensive gene catalog of the human vaginal microbiome.

Things have changed in the more than 50 years since the concept of vaginal microbiota transplants was proposed and subsequently tainted by a Texas-based gynecologist who transplanted the vaginal fluid of women who had bacterial vaginosis into healthy females, suspecting he had isolated the bacteria responsible for the condition.

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Fol­low­ing US, Chi­na hos­pi­tal ef­forts, Gilead plots its own PhI­II tri­als for close­ly watched Covid-19 drug

Gilead is launching its own Phase III trials of remdesivir, the repurposed antiviral that a WHO official called the “one drug right now we think may have real efficacy” against Covid-19 as the novel coronavirus originating from Wuhan, China ravages the world.

Announced just a day after the NIH and the University of Nebraska Medical Center registered their US-based trial online, Gilead’s program will comprise two studies enrolling around 1,000 patients beginning in March. They will recruit primarily in Asian countries but will also include patients from other locations with “high numbers of diagnosed cases,” the company said.

Bio­gen touts new ev­i­dence from the gene ther­a­py com­pa­ny it wa­gered $800M on

A year ago, Biogen made a big bet on a small gene therapy company. Now they have new evidence one of their therapies could work.

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Anthony Fauci (AP Images)

UP­DAT­ED: NIH-part­nered Mod­er­na ships off its PhI-ready coro­n­avirus vac­cine can­di­date to a sea of un­cer­tain­ty

Off it goes.

Moderna has shipped the first batch of its mRNA vaccine against SARS-CoV-2 from its manufacturing facility in Norwood, Massachusetts, to the National Institute of Allergy and Infectious Diseases in Bethesda, Maryland, for a pioneering Phase I study.

It’s a hectic race against time. In the 42 days since Moderna selected the sequence they would use to develop their vaccine — a record time, no less — the number of confirmed cases around the world has surged astronomically from a few dozen to over 80,000, per WHO and Johns Hopkins estimates.

The candidate that they came up with, mRNA-1273, encodes for a prefusion stabilized form of the spike protein, which gives the virus its crown shape and plays a key role in transmission. The Coalition for Epidemic Preparedness Innovations, the Oslo-based group better known as CEPI, funded the manufacture of this batch.

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In at least one life-sci hub, gen­der and di­ver­si­ty ini­tia­tives haven’t made a dent

Gender and racial diversity at the top of UK life science companies has hardly budged over the last seven years despite repeated advocacy efforts, according to a new report.

The report, from the recruiting firm Liftstream, found that 14.8% of directors on life sciences boards were women and 21.1% of top executives were women. That’s a modest bump from the 9.8% of directors and 18.1% of executives Liftstream identified in their last report from 2014. The percentage of women CEOs moved from 8% to 9.8%.

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Will a 'risk-of­f' mind­set has­ten cell ther­a­py M&A? Io­vance surges on buy­out chat­ter

Is it time for some cell therapy M&A?

Investors of Iovance Biotherapeutics certainly thought so, sending its stock $IOVA up as much as 40% after Bloomberg reported that the cancer-focused biotech is talking to potential buyers.

While 2019 saw a number of high-profile gene therapy company takeovers — led by Roche’s $4.3 billion bid of Spark as Astellas went for Audentes, Biogen snapped up Nightstar and Vertex absorbed Exonics — large players appeared to prefer partnering on the cell therapy front, particularly when it comes to cancer. Hal Barron put his weight behind Rick Klausner’s startup as he rebuilt GlaxoSmithKline’s cancer pipeline. Takeda turned to MD Anderson to license their natural killer cell therapy.

One less ri­val for Im­muno­vant, as Alex­ion aban­dons FcRn in­hibitor

Less than one year after Alexion parted with $25 million upfront to secure access to a second anti-FcRn asset, it is abandoning the experimental drug. The discontinuation, disclosed at the SVB Leerink Global Healthcare Conference in New York during a fireside chat, bodes well for rival Immunovant.

The drug (ABY-039), partnered for development with Sweden’s Affibody, was forsaken on the basis of early-stage data that was not viewed favorably, Baird and SVB Leerink analysts noted.