Man­u­fac­tur­ing woes de­rail a block­buster con­tender from Sanofi/Re­gen­eron. Who's next?

Sanofi wasn’t fret­ting need­less­ly over the up­com­ing FDA de­ci­sion re­gard­ing sar­ilum­ab.

The phar­ma gi­ant and its biotech part­ner Re­gen­eron $REGN an­nounced Fri­day af­ter­noon that the agency has turned thumbs down on the drug, is­su­ing a com­plete re­sponse let­ter for a drug that was wide­ly ex­pect­ed to be on a short path to a block­buster ap­proval.

As Sanofi $SNY flagged ear­li­er in its Q3 re­view, the prob­lem has more to do with the phar­ma gi­ant’s man­u­fac­tur­ing woes than Re­gen­eron’s da­ta on a drug ex­pect­ed to earn more than a bil­lion dol­lars a year.

Here’s the state­ment:

The CRL refers to cer­tain de­fi­cien­cies iden­ti­fied dur­ing a rou­tine good man­u­fac­tur­ing prac­tice in­spec­tion of the Sanofi Le Trait fa­cil­i­ty where sar­ilum­ab is filled and fin­ished, one of the last steps in the man­u­fac­tur­ing process.  Sat­is­fac­to­ry res­o­lu­tion of these de­fi­cien­cies is re­quired be­fore the BLA can be ap­proved.  Sanofi sub­mit­ted a com­pre­hen­sive cor­rec­tive ac­tion plan to the FDA and is im­ple­ment­ing the cor­rec­tive ac­tions spec­i­fied in that plan.  Sanofi is work­ing close­ly with the FDA to­wards a time­ly res­o­lu­tion that ad­dress­es these con­cerns. The CRL does not iden­ti­fy any con­cerns re­lat­ing to the safe­ty or ef­fi­ca­cy of sar­ilum­ab.

As we re­port­ed ear­li­er Fri­day, Sanofi was wor­ried that an FDA ci­ta­tion on man­u­fac­tur­ing could pre­vent reg­u­la­tors from ap­prov­ing the drug, which has al­ready beat out Hu­mi­ra in a head-to-head test on rheuma­toid arthri­tis.

A num­ber of com­pa­nies have al­so been held back this year on man­u­fac­tur­ing is­sues, in­clud­ing Por­to­la $PT­LA. On the same day that Sanofi/Re­gen­eron put out word on their set­back, Cem­pra $CEMP was al­so dinged af­ter it told in­vestors that it need­ed to scram­ble to line up a fresh sup­ply of solithromycin — now un­der re­view — af­ter reg­u­la­tors flagged is­sues with their main con­tract man­u­fac­tur­er. And the string of is­sues puts man­u­fac­tur­ing con­cerns square­ly in the cen­ter of bio­phar­ma’s prob­lems with R&D pro­duc­tiv­i­ty in 2016, as new drug ap­provals lag well be­hind last year.

Re­gen­eron can shrug off a tem­po­rary set­back like this, but Sanofi is like­ly to feel the sting.

Sanofi now ends up with a black eye on man­u­fac­tur­ing af­ter deal­ing with a re­treat on its di­a­betes fran­chise, a large­ly fruit­less so­lo R&D ef­fort and a failed ef­fort by new CEO Olivi­er Brandi­court to ac­quire Medi­va­tion. The com­pa­ny did get an OK for their PC­SK9 drug, but that launch has start­ed off much more slow­ly than ex­pect­ed.

For the phar­ma gi­ant, it’s an­oth­er sour note on a rough year. And some an­a­lysts are fret­ting that the set­back on sar­ilum­ab could trans­late in­to a prob­lem for the up­com­ing de­ci­sion on dupilum­ab, which has much big­ger im­pli­ca­tions. Leerink’s Ge­of­frey Porges, who thinks the man­u­fac­tur­ing is­sue could be re­solved in a few months, notes:

(I)f the re­me­di­a­tion is not com­plet­ed in the next 3 months, then it be­comes more ma­te­r­i­al, since it could then im­pinge on our ex­pect­ed tim­ing for the dupilum­ab ap­proval (PDU­FA date 03/29/2017). At this stage we are push­ing our time­line for sar­ilum­ab ap­proval out to mid 2017, but are leav­ing our dupilum­ab ap­proval time­line at the PDU­FA date of March 29, 2017. While five months seems more than enough time to ad­dress is­sues in a fill-fin­ish fa­cil­i­ty, the process of re-in­spec­tion, agency en­dorse­ment and then re-start­ing the ap­proval process can be sur­pris­ing­ly slow in such sit­u­a­tions.

We’ll keep you post­ed.

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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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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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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Covid-19 roundup: Mod­er­na sticks to Ju­ly for its Phase III as ru­mors swirl; Fol­low­ing US lead, EU buys up Covid-19 treat­ments

The Phase III might be delayed from its original early July goal, but Moderna says it will still kick off the pivotal study for what could ultimately be the first Covid-19 vaccine before the end of the month.

A day after Reuters reported that squabbling between the Cambridge biotech and government regulators had held up the trial by about two weeks, Moderna released a statement saying that they had completed enrollment of their 650-person Phase II trial and were on track to begin Phase III by the end of the month. The protocol for that study, which is meant to prove whether or not the vaccine can prevent people from becoming sick, has been finalized, they said.

GSK sets the stage for a toe-to-toe mar­ket show­down with Gilead­'s HIV cham­pi­on Tru­va­da

ViiV Healthcare and majority owner GlaxoSmithKline have cleared another important hurdle on a long-running quest to challenge Gilead’s dominance in preventative HIV treatments.

The final analysis of a new study shows the GSK subsidiary’s long-lasting injection, cabotegravir, proved 66% more effective in HIV prevention than Gilead’s breakthrough Truvada pill. And they now intend to carve away some of the blockbuster revenue that Gilead has enjoyed for years.

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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Stephen Hahn, AP

Trump and Navar­ro press again for hy­drox­y­chloro­quine. Can the FDA stay in­de­pen­dent?

Tuesday morning, economist and Trump advisor Peter Navarro walked onto the White House driveway and promptly brought a political cloud back onto the FDA.

Speaking to a White House pool reporter, Navarro said that four Detroit doctors were, based on a single disputed study, filing for the FDA to again issue an emergency authorization for hydroxychloroquine, the anti-malarial pill that President Trump hyped for months as a Covid-19 treatment over the objections of his own scientists. Then, while avoiding directly calling for the FDA to OK the drug, blasted the agency. He said its decision to pull an earlier authorization “was based on bad science” and “had a tremendously negative effect” on doctors and patients.

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David Hallal

AlloVir tests how much an an­tivi­ral biotech can reap in a pan­dem­ic stock mar­ket

The pandemic stock market has proven fruitful for virtually any type of biotech. Now a 7-year-old cell therapy startup will see how much it can yield for a company that specializes in fighting viruses.

AlloVir, a company that until 2019 largely lived off grant money, has filed for a $100 million IPO to back its line of off-the-shelf, virus-fighting T cells. Although in normal circumstances, $100 million could be a solid return for a biotech that got its first major round of funding only last year, we’ll have to wait to see how much the company ultimately earns. As Covid-19 has sent investor money scurrying to almost anyone in drug development, every single biotech to go public this year has prized above their midpoint or upsized their offering, according to Renaissance Capital, sometimes dramatically so.