As Ac­thar trou­bles per­sist, Mallinck­rodt in­vests in RNAi and Si­lence Ther­a­peu­tics

A day af­ter it was forced to ax an amy­otroph­ic lat­er­al scle­ro­sis study test­ing its con­tro­ver­sial Ac­thar gel, Mallinck­rodt is in­vest­ing in RNA tech­nol­o­gy to tar­get rare dis­eases by en­list­ing Si­lence Ther­a­peu­tics as a part­ner.

Si­lence Ther­a­peu­tics, akin to oth­ers in its field such as Al­ny­lam who pi­o­neered the first RNA in­ter­fer­ence ther­a­py last Au­gust, is bet­ting on the promise of si­lenc­ing the ex­pres­sion of dis­ease-caus­ing pro­teins. The land­mark dis­cov­ery of RNA in­ter­fer­ence was re­ward­ed with a No­bel prize in 2006. Though found­ed in 1994, the Lon­don biotech changed course to cham­pi­on RNA ther­a­peu­tics in 2012 — and is still in the pre­clin­i­cal phas­es with its slate of ex­per­i­men­tal drugs.

The com­pa­nies are set to co-de­vel­op RNAi ther­a­peu­tics en­gi­neered to in­hib­it the com­ple­ment cas­cade — a group of pro­teins that are in­volved in the im­mune sys­tem and that play a role in the de­vel­op­ment of in­flam­ma­tion.

As part of the agree­ment, Mallinck­rodt is get­ting an ex­clu­sive glob­al li­cense to Si­lence’s C33 com­ple­ment as­set, SLN500, as well as op­tions to li­cense up to two ad­di­tion­al com­ple­ment-tar­get­ed as­sets. The pre­clin­i­cal ther­a­py, SLN500, al­lows the com­pa­nies to tar­get a range of rare dis­eases as well as con­di­tions of im­mune dys­reg­u­la­tion.

Si­lence is in charge of pre­clin­i­cal ac­tiv­i­ties, as well as Phase I stud­ies — and Mallinck­rodt $MNK will be re­spon­si­ble for fur­ther clin­i­cal de­vel­op­ment as well as com­mer­cial­iza­tion.

Un­der the deal, Si­lence se­cures an up­front pay­ment of $20 mil­lion and is el­i­gi­ble to re­ceive up to $10 mil­lion in re­search mile­stones for SLN500 and for each op­tioned as­set, in ad­di­tion to fund­ing for Phase I clin­i­cal de­vel­op­ment in­clud­ing GMP man­u­fac­tur­ing. The SLN500 col­lab­o­ra­tion al­so pro­vides for po­ten­tial added clin­i­cal and reg­u­la­to­ry mile­stone pay­ments of up to $100 mil­lion, com­mer­cial mile­stone pay­ments of up to $563 mil­lion, in ad­di­tion to roy­al­ties.  Should Mallinck­rodt de­cide to li­cense any oth­er as­sets, Si­lence could re­ceive up to $703 mil­lion in sim­i­lar mile­stone pay­ments per as­set, in ad­di­tion to roy­al­ties.

Sep­a­rate­ly, Staines-up­on-Thames-based Mallinck­rodt al­so in­ject­ed $5 mil­lion in­to Si­lence Ther­a­peu­tics, in ex­change for about 5.1 mil­lion shares from its part­ner.

The more than 150-year-old com­pa­ny has a suite of spe­cial­ty med­i­cines and gener­ic treat­ments in its ar­se­nal of drugs, but its Ac­thar gel — which it ac­quired in 2014 with the takeover of Quest­cor — ac­count­ed for a lit­tle over a third of Mallinck­rodt’s rough­ly $3.2 bil­lion in net sales last year.

The prod­ucts list price has been hiked from $40 per vial in 2001 to a whop­ping $38,892 cur­rent­ly. Ex­tract­ed from the pi­tu­itary glands of slaugh­tered pigs, it’s man­u­fac­tured es­sen­tial­ly the same way as it was in the 1950s, and is cleared for use in 19 in­di­ca­tions. The drug­mak­er has there­fore long elicit­ed the ire of reg­u­la­to­ry agen­cies for its mar­ket­ing prac­tices in re­la­tion to Ac­thar.

In May, Mallinck­rodt was dealt a heavy blow when the Cen­ters for Medicare & Med­ic­aid Ser­vices de­cid­ed to re­vert to the base date av­er­age man­u­fac­tur­er price on Ac­thar from the rate used since 2013, which was pri­or to the com­pa­ny’s ac­qui­si­tion of Quest­cor. “(T)he shift will sub­stan­tial­ly raise the cal­cu­lat­ed re­bate such that the net re­al­ized price on Ac­thar sales to Med­ic­aid ben­e­fi­cia­ries will fall from the cur­rent ~$30k+ per vial to ‘dol­lars’ per vial. With Med­ic­aid rep­re­sent­ing ~10% of Ac­thar sales, the shift if put in­to ef­fect would im­pact an­nu­al sales by ~$100 mil­lion per year. In re­sponse, MNK has filed for in­junc­tive re­lief un­der the Ad­min­is­tra­tive Pro­ce­dure Act (APA) where the time­line is ex­pect­ed to be ex­pe­dit­ed; hence a fi­nal rul­ing should at some point in the 2Q-3Q time­frame,” Jef­feries an­a­lysts wrote in a note.

Brian Kaspar. AveXis via Twitter

AveX­is sci­en­tif­ic founder fires back at No­var­tis CEO Vas Narasimhan, 'cat­e­gor­i­cal­ly de­nies any wrong­do­ing'

Brian Kaspar’s head was among the first to roll at Novartis after company execs became aware of the fact that manipulated data had been included in its application for Zolgensma, now the world’s most expensive therapy.

But in his first public response, the scientific founder at AveXis — acquired by Novartis for $8.7 billion — is firing back. And he says that not only was he not involved in any wrongdoing, he’s ready to defend his name as needed.

I reached out to Brian Kaspar after Novartis put out word that he and his brother Allen had been axed in mid-May, two months after the company became aware of the allegations related to manipulated data. His response came back through his attorneys.

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UP­DAT­ED: An em­bold­ened As­traZeneca splurges $95M on a pri­or­i­ty re­view vouch­er. Where do they need the FDA to hus­tle up?

AstraZeneca is in a hurry.

We learned this morning that the pharma giant — not known as a big spender, until recently — forked over $95 million to get its hands on a priority review voucher from Sobi, otherwise known as Swedish Orphan Biovitrum.

That marks another step down on price for a PRV, which allows the holder to slash 4 months off of any FDA review time.

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Martin Shkreli [via Getty]

Pris­on­er #87850-053 does not get to add drug de­vel­op­er to his list of cred­its

Just days after Retrophin shed its last ties to founder Martin Shkreli, the biotech is reporting that the lead drug he co-invented flopped in a pivotal trial. Fosmetpantotenate flunked both the primary and key secondary endpoints in a placebo-controlled trial for a rare disease called pantothenate kinase-associated neurodegeneration, or PKAN.

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We­bi­nar: Re­al World End­points — the brave new world com­ing in build­ing fran­chise ther­a­pies

Several biopharma companies have been working on expanding drug labels through the use of real world endpoints, combing through the data to find evidence of a drug’s efficacy for particular indications. But we’ve just begun. Real World Evidence is becoming an important part of every clinical development plan, in the soup-through-nuts approach used in building franchises.

I’ve recruited a panel of 3 top experts in the field — the first in a series of premium webinars — to look at the practical realities governing what can be done today, and where this is headed over the next few years, at the prodding of the FDA.

ZHEN SU — Merck Serono’s Senior Vice President and Global Head of Oncology
ELLIOTT LEVY — Amgen’s Senior Vice President of Global Development
CHRIS BOSHOFF — Pfizer Oncology’s Chief Development Officer

A premium subscription to Endpoints News is required to attend this webinar. Please upgrade to either an Insider or Enterprise plan for access. Already have Endpoints Premium? Please sign-in below. You can contact our Subscriptions team at with any issues.

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Am­gen, Al­ler­gan biosim­i­lar of Roche's block­buster Rit­ux­an clears an­oth­er US piv­otal study 

Novartis $NVS may have given up, but Amgen $AMGN and Allergan $AGN are plowing ahead with their knockoff of Roche’s blockbuster biologic Rituxan in the United States.

Their copycat, ABP 798, was found to have a clinically equivalent impact as Rituxan — meeting the main goal of the study involving CD20-positive B-cell non-Hodgkin’s lymphoma patients. This is the second trial supporting the profile of the biosimilar. In January, it came through with positive PK results in patients with rheumatoid arthritis.

BeiGene and Mus­tang nail down spe­cial FDA sta­tus for top drugs; Roche bags added cov­er­age for Hem­li­bra

→ BeiGene $BGNE is getting a boost in its drive to field a rival to Imbruvica. The FDA has offered an accelerated review to zanubrutinib, a BTK inhibitor that has posted positive results for mantle cell lymphoma. The PDUFA date lands on February 27, 2020. The drug scored breakthrough status at the beginning of the year.

→ BeiGene isn’t the only biopharma company to gain special regulatory status today. Mustang Bio $MBIO and St. Jude Children’s Research Hospital announced that MB-107, a lentiviral gene therapy for the treatment of X-linked severe combined immunodeficiency, also known as bubble boy disease, has been granted Regenerative Medicine Advanced Therapy status.

Trump ad­min­is­tra­tion re­vives bid to get drug list prices on TV ads

The Trump administration is not giving up just yet. On Wednesday, the HHS filed an appeal against a judge’s decision in July to overturn a ruling obligating drug manufacturers to disclose the list price of their therapies in television adverts — hours before it was stipulated to go into effect.

In May, the HHS published a final ruling requiring drugmakers to divulge the wholesale acquisition cost— of a 30-day supply of the drug — in tv ads in a bid to enhance price transparency in the United States. The pharmaceutical industry has vehemently opposed the rule, asserting that list prices are not what a typical patient in the United States pays for treatment — that number is typically determined by the type of (or lack thereof) insurance coverage, deductibles and out-of-pocket costs. Although there is truth to that claim, the move was considered symbolic in the Trump administration’s healthcare agenda to hold drugmakers accountable in a climate where skyrocketing drug prices have incensed Americans on both sides of the aisle.

Bob Smith, Pfizer

Pfiz­er is mak­ing a $500M state­ment to­day: Here’s how you be­come a lead play­er in the boom­ing gene ther­a­py sec­tor

Three years ago, Pfizer anted up $150 million in cash to buy Bamboo Therapeutics in Chapel Hill, NC as it cautiously stuck a toe in the small gene therapy pool of research and development.

Company execs followed up a year later with a $100 million expansion of the manufacturing operations they picked up in that deal for the UNC spinout, which came with $495 million in milestones.

And now they’re really going for it.

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Video: Putting the AI in R&D — with Badhri Srini­vasan, Tony Wood, Rosana Kapeller, Hugo Ceule­mans, Saurabh Sa­ha and Shoibal Dat­ta

During BIO this year, I had a chance to moderate a panel among some of the top tech experts in biopharma on their real-world use of artificial intelligence in R&D. There’s been a lot said about the potential of AI, but I wanted to explore more about what some of the larger players are actually doing with this technology today, and how they see it advancing in the future. It was a fascinating exchange, which you can see here. The transcript has been edited for brevity and clarity. — John Carroll