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.

Michel Vounatsos, Biogen CEO (via YouTube)

UP­DAT­ED: Bio­gen spot­lights a pair of painful pipeline set­backs as ad­u­canum­ab show­down looms at the FDA

Biogen has flagged a pair of setbacks in the pipeline, spotlighting the final failure for a one-time top MS prospect while scrapping a gene therapy for SMA after the IND was put on hold due to toxicity.

Both failures will raise the stakes even higher on aducanumab, the Alzheimer’s drug that Biogen is betting the ranch on, determined to pursue an FDA OK despite significant skepticism they can make it with mixed results and a reliance on post hoc data mining. And the failures are being reported as Biogen was forced to cut its profit forecast for 2020 as a generic rival started to erode their big franchise drug.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 92,200+ biopharma pros reading Endpoints daily — and it's free.

A new chap­ter in the de­cen­tral­ized clin­i­cal tri­al ap­proach

Despite the promised decentralized trial revolution, we haven’t yet moved the needle in a significant way, although we are seeing far bolder commitments to this as we continue to experience the pandemic restrictions for some time to come. The vision of grandeur is one thing, but operationalizing and execution are another and recognising that change, particularly mid-flight on studies, is worthy of thorough evaluation and consideration in order to achieve success. Here we will discuss one of the critical building blocks of a Decentralized and Remote Trial strategy: TeleConsent; more than paper under glass, it is a paradigm change and key digital enabler.

Stephen Hahn, FDA commissioner (AP Images)

As FDA sets the stage for the first Covid-19 vac­cine EUAs, some big play­ers are ask­ing for a tweak of the guide­lines

Setting the stage for an extraordinary one-day meeting of the Vaccines and Related Biological Products Advisory Committee this Thursday, the FDA has cleared 2 experts of financial conflicts to help beef up the committee. And regulators went on to specify the safety, efficacy and CMC input they’re looking for on EUAs, before they move on to the full BLA approval process.

All of this has already been spelled out to the developers. But the devil is in the details, and it’s clear from the first round of posted responses that some of the top players — including J&J and Pfizer — would like some adjustments and added feedback. And on Thursday, the experts can offer their own thoughts on shaping the first OKs.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 92,200+ biopharma pros reading Endpoints daily — and it's free.

UP­DAT­ED: CRISPR Ther­a­peu­tics gets a snap­shot of off-the-shelf CAR-T suc­cess in B-cell ma­lig­nan­cies — marred by the death of a pa­tient

Just days after scientific founder Emmanuelle Charpentier shared the Nobel prize for her work on CRISPR/Cas9, CRISPR Therapeutics $CRSP is showing off a snapshot of success in their early-stage study for an off-the-shelf CAR-T approach to CD19+ B cell malignancies — a snapshot marred by the death of a patient who had been given a high dose of the treatment.

Using their gene editing tech, researchers for CRISPR engineered cells from healthy donors into an attack vehicle aimed at cancer, something that has been achieved with great success using patients’ own cells — the autologous approach. But autologous CAR-T is hampered by the more complex vein-to-vein requirement that delays treatment, and now CRISPR Therapeutics along with other players like Allogene are determined to replace the pioneers with CAR-T 2.0.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 92,200+ biopharma pros reading Endpoints daily — and it's free.

RBC's Bri­an Abra­hams holds a mock ad­comm on Bio­gen's iffy ad­u­canum­ab da­ta — and most of these ex­perts don't see a path to an ap­proval

As catalysts go, few loom larger than the aducanumab adcomm slated for Nov. 6.

With its big franchise under assault, Biogen is betting the ranch that its mixed late-stage Alzheimer’s data can squeak past the experts and regulators and get onto the market. And the topic — after a decade of Alzheimer’s R&D disasters in what still represents the El Dorado of drug markets — remains in the center ring of discussions around late-stage pipeline prospects.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 92,200+ biopharma pros reading Endpoints daily — and it's free.

Philipp Spycher

Promis­ing bet­ter link­er tech to ADC field, Araris has 'very, very am­bi­tious' plans for the clin­ic

A couple months after raising CHF 2.5 million ($2.76 million) in initial seed funding, one-year-old Araris Biotech is topping off the round with another CHF 12.7 million ($14 million).

The Paul Scherrer Institute and ETH Zurich spinout now has CHF 15.2 million to work with, and CEO Philipp Spycher has big plans. He hopes to bring one of the company’s antibody-drug conjugates (ADC) to the clinic by late 2022 or early 2023. “It’s very, very ambitious, but we are very optimistic that we actually can make it,” he said.

Roche finds a home for a new, $500M man­u­fac­tur­ing lo­gis­tics hub, promis­ing 500 jobs

Roche is pouring $500 million into its Canadian headquarters in Mississauga, Ontario to set up a new hub that will coordinate logistics for its global supply chain.

Over the 5-year investment, the Swiss pharma giant expects to add 200 jobs over next year and another 300 by the end of 2023.

Introduced as a $190 million global pharmaceutical development site in 2011, the campus currently houses Roche’s Canadian commercial unit as well as product development, global procurement and pharma informatics. The new expansion will see it organize manufacturing across 13 plants and 11 sites, according to FiercePharma.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 92,200+ biopharma pros reading Endpoints daily — and it's free.

David Hung (file photo)

Mas­ter deal­mak­er David Hung re­tools a SPAC sedan in­to a fi­nanc­ing mus­cle ve­hi­cle that leaves his can­cer start­up with $850M and a place on Wall Street

It’s only right that one of the industry’s top dealmakers just completed one of the biggest SPAC-related deals in the pipeline.

David Hung, of Medivation fame, has completed a back flip into the market, merging with EcoR1 Capital’s SPAC Panacea and landing neatly on Wall Street with an $NUVB stock ticker after filling out the blank check in his name. In addition to the $144 million held in the SPAC — provided none of the investors opt out — Hung is getting ahold of $500 million more being chipped in by a slate of institutional investors who feel that Hung could have the keys to another Medivation-style success.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 92,200+ biopharma pros reading Endpoints daily — and it's free.

Years af­ter a ma­jor tri­al set­back, No­var­tis switch­es gears with SMA drug. This time they're try­ing it for Hunt­ing­ton's

Four years after a Phase I/II setback in spinal muscular atrophy (SMA), Novartis is hoping its drug branaplam will find more success in a new neurological indication: Huntington’s disease.

The decision was announced a year after the head of research, Jay Bradner, said he did not see a “big opportunity” in SMA, according to Reuters. Novartis says it has preclinical data showing that branaplam reduces levels of mutant huntingtin protein, and SMA data showing patients on the drug had reductions in huntingtin mRNA. The FDA gave branaplam their orphan drug designation, and Novartis plans to move forth with a Phase IIb trial next year.