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.

Im­ple­ment­ing re­silience in the clin­i­cal tri­al sup­ply chain

Since January 2020, the clinical trials ecosystem has quickly evolved to manage roadblocks impeding clinical trial integrity, and patient care and safety amid a global pandemic. Closed borders, reduced air traffic and delayed or canceled flights disrupted global distribution, revealing how flexible logistics and supply chains can secure the timely delivery of clinical drug products and therapies to sites and patients.

John Maraganore, Alnylam CEO (Scott Eisen/Bloomberg via Getty Images)

Al­ny­lam gets the green light for drug #3 — and CEO John Maraganore is ready to roll

Score another early win at the FDA for Alnylam.

The FDA put out word today that the agency has approved its third drug, lumasiran, for primary hyperoxaluria type 1, better known as PH1.

An ultra rare genetic condition, Alnylam CEO John Maraganore says there are only some 1,000 to 1,700 patients in the US and Europe at any particular point. The patients, mostly kids, suffer from an overproduction of oxalate in the liver that spurs the development of kidney stones, right through to end stage kidney disease.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 94,100+ biopharma pros reading Endpoints daily — and it's free.

In fi­nal days at Mer­ck, Roger Perl­mut­ter bets big on a lit­tle-known Covid-19 treat­ment

Roger Perlmutter is spending his last days at Merck, well, spending.

Two weeks after snapping up the antibody-drug conjugate biotech VelosBio for $2.75 billion, Merck announced today that it had purchased OncoImmune and its experimental Covid-19 drug for $425 million. The drug, known as CD24Fc, appeared to reduce the risk of respiratory failure or death in severe Covid-19 patients by 50% in a 203-person Phase III trial, OncoImmune said in September.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 94,100+ biopharma pros reading Endpoints daily — and it's free.

Pascal Soriot (AP Images)

UP­DAT­ED: As­traZeneca, Ox­ford on the de­fen­sive as skep­tics dis­miss 70% av­er­age ef­fi­ca­cy for Covid-19 vac­cine

On the third straight Monday that the world wakes up to positive vaccine news, AstraZeneca and Oxford are declaring a new Phase III milestone in the fight against the pandemic. Not everyone is convinced they will play a big part, though.

With an average efficacy of 70%, the headline number struck analysts as less impressive than the 95% and 94.5% protection that Pfizer/BioNTech and Moderna have boasted in the past two weeks, respectively. But the British partners say they have several other bright spots going for their candidate. One of the two dosing regimens tested in Phase III showed a better profile, bringing efficacy up to 90%; the adenovirus vector-based vaccine requires minimal refrigeration, which may mean easier distribution; and AstraZeneca has pledged to sell it at a fraction of the price that the other two vaccine developers are charging.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 94,100+ biopharma pros reading Endpoints daily — and it's free.

Bahija Jallal (file photo)

TCR pi­o­neer Im­muno­core scores a first with a land­mark PhI­II snap­shot on over­all sur­vival for a rare melanoma

Bahija Jallal’s crew at TCR pioneer Immunocore says they have nailed down a promising set of pivotal data for their lead drug in a frontline setting for a solid tumor. And they are framing this early interim readout as the convincing snapshot they need to prove that their platform can deliver on a string of breakthrough therapies now in the clinic or planned for it.

In advance of the Monday announcement, Jallal and R&D chief David Berman took some time to walk me through the first round of Phase III data for their lead TCR designed to treat rare, frontline cases of metastatic uveal melanoma that come with a grim set of survival expectations.

Endpoints Premium

Premium subscription required

Unlock this article along with other benefits by subscribing to one of our paid plans.

Bob Nelsen (Photo by Michael Kovac/Getty Images)

Bob Nelsen rais­es $800M and re­cruits a star-stud­ded board to build the 'Fox­con­n' of biotech

Bob Nelsen spent his pandemic spring in his Seattle home, talking on the phone with Luciana Borio, the scientist who used to run pandemic preparedness on the National Security Council, and fuming with her about the dire state of American manufacturing.

Companies were rushing to develop vaccines and antibodies for the new virus, but even if they succeeded, there was no immediate supply chain or infrastructure to mass-produce them in a way that could make a dent in the outbreak.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 94,100+ biopharma pros reading Endpoints daily — and it's free.

Am­gen sev­ers 14-year Cy­to­ki­net­ics part­ner­ship, bail­ing on ome­cam­tiv af­ter mixed PhI­II re­sults

Amgen is shrugging off a 14-year development alliance and the tens of millions of dollars spent to develop a new heart drug at Cytokinetics after a Phase III trial turned up weak data — leaving Cytokinetics to soldier on alone.

Omecamtiv mecarbil technically worked, meeting the primary composite endpoint in the Phase III GALACTIC-HF study. But it missed a key secondary endpoint, which analysts had been following as a key marker for success — reduction of cardiovascular (CV) death. While Cytokinetics celebrated the results, its stock tanked 43% upon the news, and analysts warned of an uncertain path ahead. Now, Amgen wants out.

Carl Hansen, AbCellera CEO (University of British Columbia)

From a pair of Air Jor­dans to a $200M-plus IPO, Carl Hansen is craft­ing an overnight R&D for­tune fu­eled by Covid-19

Back in the summer of 2019, Carl Hansen left his post as a professor at the University of British Columbia to go full time as the CEO at a low-profile antibody shop he had founded called AbCellera.

As biotech CEOs go, even after a fundraise Hansen wasn’t paid a whole heck of a lot. He ended up earning right at $250,000 for the year. His compensation package included a loan — which he later paid back — and a pair of Air Jordan tennis shoes. His newly-hired CFO, Andrew Booth, got a sweeter pay packet than that — which included his own pair of Air Jordans.

Endpoints Premium

Premium subscription required

Unlock this article along with other benefits by subscribing to one of our paid plans.

Leonard Schleifer, Regeneron CEO (Andrew Harnik/AP)

Trail­ing Eli Lil­ly by 12 days, Re­gen­eron gets the FDA OK for their Covid-19 an­ti­body cock­tail

A month and a half after becoming the experimental treatment of choice for a newly diagnosed president, Regeneron’s antibody cocktail has received emergency use authorization from the FDA. It will be used to treat non-hospitalized Covid-19 patients who are at high-risk of progressing.

Although the Rgeneron drug is not the first antibody treatment authorized by the FDA, the news comes as a significant milestone for a company and a treatment scientists have watched closely since the outbreak began.