Eye­ing one of the first RNAi ther­a­pies and cho­les­terol block­buster, Med­Co shows de­tailed in­clisir­an da­ta

The main ques­tion was not whether it would work; it was if it would be safe.

The Med­i­cines Com­pa­ny is out with new da­ta on its LDL cho­les­terol drug in­clisir­an, and they con­firm the first, ten­ta­tive an­swers: Yes. They al­so keep Med­Co on track for an im­mi­nent  FDA sub­mis­sion for one of the first RNAi ther­a­pies and a drug that could flip the cho­les­terol mar­ket. An EU ap­pli­ca­tion will fol­low in the first quar­ter of 2020.

Pre­sent­ing de­tailed re­sults from the sec­ond of three Phase III in­clisir­an tri­als at the Amer­i­can Heart As­so­ci­a­tion Con­gress, Med­Co showed the drug had sim­i­lar safe­ty met­rics as a place­bo in pa­tients with ath­er­o­scle­rot­ic car­dio­vas­cu­lar dis­ease (AS­CVD) and el­e­vat­ed LDL cho­les­terol. Med­Co an­nounced in Sep­tem­ber the tri­al had met all ef­fi­ca­cy end­points and ap­peared safe but re­leased no da­ta.

The new re­sults showed ad­verse events rates equal to or small­er than the place­bo group. The ORI­ON-10 re­sults al­so showed a greater de­gree of LDL-C low­er­ing than the ear­li­er ORI­ON-11 tri­al. At day 510, LDL-C re­duc­tions were at 58%, com­pared with the 54% dis­played in ORI­ON-11, a dif­fer­ence that may re­flect slight­ly dif­fer­ent pa­tient pop­u­la­tions.

“ORI­ON-10 re­sults met our high ex­pec­ta­tions,” SVB Leerink’s Joseph Schwartz wrote.

The new da­ta comes not long af­ter Re­gen­eron and Am­gen slashed prices on two drugs once billed as the next gen­er­a­tion block­busters of cho­les­terol ther­a­pies. Pralu­ent and Repatha, both mon­o­clon­al an­ti­bod­ies that blocked the PC­SK9 en­zyme, dra­mat­i­cal­ly low­ered LDL in Phase III tri­als, but pay­ers balked at the ini­tial cost: A lit­tle over $14,000.

SVB Leerink’s Mani Foroohar has mod­eled in­clisir­an at a price around $5,000, or slight­ly less than what the PC­SK9 in­hibitors are now go­ing for. An­a­lysts have al­so pre­dict­ed it will be­come the top sell­er by virtue of its dos­ing sched­ule: twice per year. The an­ti­bod­ies are ad­min­is­tered twice per month.

“We be­lieve this dos­ing sched­ule is at­trac­tive to pa­tients and can im­prove ad­her­ence since cur­rent­ly, on­ly 55-60% of pa­tients are com­pli­ant on PC­SK9 Ab ther­a­py,” Jef­feries has not­ed.

But first, it had to clear safe­ty hur­dles, par­tic­u­lar­ly giv­en the new­ness of the RNAi tech. The ORI­ON-10 study of 1,561 pa­tients showed sim­i­lar rates of se­ri­ous ad­verse events in the two arms (26.3% in place­bo vs. 22.4% in treat­ment), death in­ci­dence (1.4% vs 1.5%), and ma­lig­nan­cies (3.3% in both).

De­tails from the fi­nal study, ORI­ON-9 in pa­tients with het­erozy­gous fa­mil­ial hy­per­c­ho­les­terolemia will be pre­sent­ed lat­er to­day. Topline da­ta from that study re­leased in Sep­tem­ber showed the drug meet­ing all pri­ma­ry and sec­ondary ef­fi­ca­cy end­points and dis­play­ing an “ex­cel­lent” safe­ty pro­file.

As one of the first small RNA in­ter­fer­ence ther­a­pies, an ap­proval would have sig­nif­i­cance be­yond the car­dio­vas­cu­lar world. Based on a process first hint­ed at in a 1990 ex­per­i­ment on petu­nia, it us­es a built-in process, cells have to dice up virus RNA or mes­sen­ger RNA it doesn’t want to code. (For an ex­pla­na­tion of the ba­sic sci­ence at play for you or your 5th grad­er, see this food-based Ted Ed.)

Rather than block the LDL-build­ing PC­SK9 pro­tein, Med­Co in­jects pa­tients with lit­tle bits of RNA that im­pedes cells from cre­at­ing the pro­tein al­to­geth­er. The first RNAi ther­a­py was ap­proved last year: a rare dis­ease treat­ment from Al­ny­lam.

Regeneron CEO Leonard Schleifer speaks at a meeting with President Donald Trump, members of the Coronavirus Task Force, and pharmaceutical executives in the Cabinet Room of the White House (AP Photo/Andrew Harnik)

OWS shifts spot­light to drugs to fight Covid-19, hand­ing Re­gen­eron $450M to be­gin large scale man­u­fac­tur­ing in the US

The US government is on a spending spree. And after committing billions to vaccines defense operations are now doling out more of the big bucks through Operation Warp Speed to back a rapid flip of a drug into the market to stop Covid-19 from ravaging patients — possibly inside of 2 months.

The beneficiary this morning is Regeneron, the big biotech engaged in a frenzied race to develop an antibody cocktail called REGN-COV2 that just started a late-stage program to prove its worth in fighting the virus. BARDA and the Department of Defense are awarding Regeneron a $450 million contract to cover bulk delivery of the cocktail starting as early as late summer, with money added for fill/finish and storage activities.

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Atul Deshpande, Harbour BioMed chief strategy officer & head, US operations (Harbour BioMedO

An­oth­er biotech IPO set-up? Multi­na­tion­al biotech leaps from round to round, scoop­ing up cash at a blis­ter­ing pace

A short four months after announcing a $75 million haul in Series B+ fundraising, the multinational biotech Harbour BioMed pulled in another round of investments and eclipsed the nine-digit mark in the process.

Harbour completed its Series C financing, the company announced Thursday morning, raising $102.8 million and bringing its total investment sum to over $300 million since its founding in late 2016. The biotech plans to use the money to transition early-stage candidates from the discovery phase, fund candidates already in the clinic, and prep late-stage candidates for commercialization.

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UP­DAT­ED: Bio­gen shares spike as ex­ecs com­plete a de­layed pitch for their con­tro­ver­sial Alzheimer's drug — the next move be­longs to the FDA

Biogen is stepping out onto the high wire today, reporting that the team working on the controversial Alzheimer’s drug aducanumab has now completed their submission to the FDA. And they want the agency to bless it with a priority review that would cut the agency’s decision-making time to a mere 6 months.

The news drove a 10% spike in Biogen’s stock $BIIB ahead of the bell.

Part of that spike can be attributed to a relief rally. Biogen execs rattled backers and a host of analysts earlier in the year when they unexpectedly delayed their filing to the third quarter. That delay provoked all manner of speculation after CEO Michel Vounatsos and R&D chief Al Sandrock failed to persuade influential observers that the pandemic and other factors had slowed the timeline for filing. Actually making the pitch at least satisfies skeptics that the FDA was not likely pushing back as Biogen was pushing in. From the start, Biogen execs claimed that they were doing everything in cooperation with the FDA, saying that regulators had signaled their interest in reviewing the submission.

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Ed Engleman (Stanford Blood Center)

Stan­ford star on­col­o­gy sci­en­tist Ed En­gle­man helped cre­ate the im­munother­a­py field. Now he wants to shake up neu­rode­gen­er­a­tion R&D

Over the last generation of drug R&D, Ed Engleman has been a standout scientist.

The Stanford professor co-founded Dendreon and provided the scientific insights needed to develop Provenge into a pioneering — though not particularly marketable — immunotherapy. He’s spurred a slate of startups, assisted by his well-connected perch as a co-founder of Vivo Capital, and took the dendritic cell story into its next chapter at a startup called Bolt.

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Nello Mainolfi (Kymera via YouTube)

Out to re­vive R&D, a resur­gent Sanofi pays $150M cash to part­ner up with a pi­o­neer­ing pro­tein degra­da­tion play­er

Frank Nestle was appointed Sanofi’s global head of immunology and inflammation research therapeutic area just days before dupilumab, the blockbuster-to-be IL-4 antibody, would be accepted for priority review. After four years of consolidating immunology expertise from multiple corners of the Sanofi family and recruiting new talents to build the discovery engine, he’s set eyes on a Phase I-ready program that he believes can grow into a Dupixent-sized franchise.

Covid-19 roundup: CDC de­bat­ing who should get first avail­able vac­cines; EU in Gilead talks af­ter US gob­bled first remde­sivir dos­es

The federal government has now spent billions of dollars accelerating the development of a Covid-19 vaccine, and yet they’ve remained hush-hush on who, precisely, would actually get inoculated once the first doses are approved and available. Internally, though, they have been debating it.

The CDC and an advisory committee of outside health experts have been working since April to devise a ranking system that would determine who receives a vaccine and when, The New York Times reported. The question of who is first in line for inoculation is important because no matter how many doses developers can make or how quickly they can make them, doses will still come out in batches; 300 million inoculations will not appear overnight.

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Daniel O'Day, Gilead CEO (Kevin Dietsch/UPI/Bloomberg via Getty Images)

A new study points to $6.5B in pub­lic sup­port build­ing the sci­en­tif­ic foun­da­tion of Gilead­'s remde­sivir. Should that be re­flect­ed in the price?

By drug R&D standards, Gilead’s move to repurpose remdesivir for Covid-19 and grab an emergency use authorization was a remarkably easy, low-cost layup that required modest efficacy and a clean safety profile from just a small group of patients.

The drug OK also arrived after Gilead had paid much of the freight on getting it positioned to move fast.

In a study by Fred Ledley, director of the Center for Integration of Science and Industry at Bentley University in Waltham, MA, researchers concluded that the NIH had invested only $46.5 million in the research devoted to the drug ahead of the pandemic, a small sum compared to the more than $1 billion Gilead expected to spend getting it out this year, all on top of what it had already cost in R&D expenses.

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FDA bars the door — for now — against Mer­ck’s star can­cer drug af­ter Roche beat them to the punch

Merck has been handed a rare setback at the FDA.

After filing for the accelerated approval of a combination of their star PD-1 drug Keytruda with Eisai’s Lenvima as a first-line treatment for unresectable hepatocellular carcinoma, the FDA nixed the move, handing out a CRL because Roche beat them to the punch on the same indication by a matter of weeks.

According to Merck:

Ahead of the Prescription Drug User Fee Act action dates of Merck’s and Eisai’s applications, another combination therapy was approved based on a randomized, controlled trial that demonstrated overall survival. Consequently, the CRL stated that Merck’s and Eisai’s applications do not provide evidence that Keytruda in combination with Lenvima represents a meaningful advantage over available therapies for the treatment of unresectable or metastatic HCC with no prior systemic therapy for advanced disease. Since the applications for KEYNOTE-524/Study 116 no longer meet the criteria for accelerated approval, both companies plan to work with the FDA to take appropriate next steps, which include conducting a well-controlled clinical trial that demonstrates substantial evidence of effectiveness and the clinical benefit of the combination.

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Donald and Melania Trump watch the smoke of fireworks from the South Lawn of the White House on July 4, 2020 (via Getty)

Which drug de­vel­op­ers of­fer Trump a quick, game-chang­ing ‘so­lu­tion’ as the pan­dem­ic roars back? Eli Lil­ly and Ab­Cellera look to break out of the pack

We are unleashing our nation’s scientific brilliance and will likely have a therapeutic and/or vaccine solution long before the end of the year.

— Donald Trump, July 4

Next week administration officials plan to promote a new study they say shows promising results on therapeutics, the officials said. They wouldn’t describe the study in any further detail because, they said, its disclosure would be “market-moving.”

— NBC News, July 3

Something’s cooking. And it’s not just July 4 leftovers involving stale buns and uneaten hot dogs.

Over the long weekend observers picked up signs that the focus in the Trump administration may swiftly shift from the bright spotlight on vaccines being promised this fall, around the time of the election, to include drugs that could possibly keep patients out of the hospital and take the political sting out of the soaring Covid-19 numbers causing embarrassment in states that swiftly reopened — as Trump cheered along.

So far, Gilead has been the chief beneficiary of the drive on drugs, swiftly offering enough early data to get remdesivir an emergency authorization and into the hands of the US government. But their drug, while helpful in cutting stays, is known for a limited, modest effect. And that won’t tamp down on the hurricane of criticism that’s been tearing at the White House, and buffeting the president’s most stalwart core defenders as the economy suffers.

We’ve had positive early-stage vaccine data, most recently from Pfizer and BioNTech, playing catchup on an mRNA race led by Moderna — where every little sign of potential trouble is magnified into a lethal threat, just as every advance excites a frenzy of support. But that race still has months to play out, with more Phase I data due ahead of the mid-stage numbers looming ahead. A vaccine may not be available in large enough quantities until well into 2021, which is still wildly ambitious.

So what about a drug solution?

Trump’s initial support for a panacea focused on hydroxychloroquine. But that fizzled in the face of data underscoring its ineffectiveness — killing trials that aren’t likely to be restarted because of a recent population-based study offering some support. And there are a number of existing drugs being repurposed to see how they help hospitalized patients.

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