FDA dis­miss­es Alk­er­mes’ pitch on ‘5461, de­mand­ing new de­pres­sion tri­als in a dam­ag­ing set­back

Alk­er­mes $ALKS made a high-stakes gam­ble that the FDA would con­sid­er ap­prov­ing their big de­pres­sion drug ALKS-5461 on the ba­sis of a sin­gle pos­i­tive Phase III study — and they lost. The biotech re­port­ed Mon­day morn­ing that the agency had is­sued a refuse-to-file let­ter for the drug, se­ri­ous­ly de­lay­ing any shot at an OK.

Ac­cord­ing to the com­pa­ny state­ment, the FDA is de­mand­ing more clin­i­cal tri­als to pro­vide a full set of da­ta as well as a “bioavail­abil­i­ty study to gen­er­ate ad­di­tion­al bridg­ing da­ta be­tween ALKS 5461 and the ref­er­ence list­ed drug, buprenor­phine.”

Alk­er­mes’ shares im­me­di­ate­ly plunged more than 20% in pre-mar­ket trad­ing, wip­ing out close to $2 bil­lion in mar­ket cap.

Fac­ing years of ex­pen­sive new clin­i­cal tri­al work, Alk­er­mes ex­ecs im­me­di­ate­ly served no­tice that they plan to ap­peal the de­ci­sion.

“We strong­ly be­lieve that the clin­i­cal de­vel­op­ment pro­gram, in­clud­ing da­ta from more than 1,500 pa­tients with MDD, pro­vides sub­stan­tial ev­i­dence of ALKS 5461’s con­sis­tent an­ti­de­pres­sant ac­tiv­i­ty and a fa­vor­able ben­e­fit-risk pro­file,” said CEO Richard Pops.

“To say we were sur­prised is an un­der­state­ment,” Pops said in a call with an­a­lysts Mon­day, not­ing all the da­ta that were gath­ered to­geth­er and their on­go­ing dis­cus­sions with the FDA through the fil­ing.

An­a­lysts im­me­di­ate­ly start­ed as­sess­ing the dam­age, which will be sig­nif­i­cant.

“This is crit­i­cal and is clear­ly be­low ex­pec­ta­tions,” not­ed Ever­core ISI’s Umer Raf­fat. “It was my base case that the on­go­ing add’l Ph 3 would suf­fice … but that doesn’t ap­pear to be the case.”

Asked if Alk­er­mes was pre­pared to go ahead with a new Phase III pro­gram, Pops de­murred.

“I think the smart thing to do is to wait to see the whites of the FDA’s eyes in a Type A meet­ing,” he said.

Their drug hit back-to-back Phase III fail­ures ear­ly in 2017, send­ing the com­pa­ny’s stock in­to a tail­spin. But a re­designed third Phase III hit with pos­i­tive da­ta, en­cour­ag­ing Pops to be­lieve that he could make a case for the drug by com­bin­ing all of the da­ta. De­vel­op­ers typ­i­cal­ly set up a trio of piv­otal tri­als in de­pres­sion, hop­ing that two out of three can es­cape be­ing tak­en down by a high place­bo re­sponse.

Pops start­ed to re­build the ar­gu­ment for this drug be­fore the ini­tial Phase III dust­up had qui­et­ed down. The com­pa­ny cit­ed a trend to­ward sta­tis­ti­cal sig­nif­i­cance and not­ed that a post hoc analy­sis as­cer­tained that the en­tire 2mg/2mg dose group in one study — FOR­WARD-4 — achieved the crit­i­cal end­point on the Mont­gomery–Ås­berg De­pres­sion Rat­ing Scale (MADRS-6) scores. Re­searchers went back to the draw­ing board, adding new pa­tients and re­jig­ging its sta­tis­ti­cal analy­sis plan for FOR­WARD-5.

FOR­WARD-3 sim­ply failed, says Alk­er­mes, due to a high place­bo re­sponse, a com­mon fea­ture in de­pres­sion. Un­like For­ward-4 and For­ward-5, though, For­ward-3 did not use what’s called a se­quen­tial par­al­lel com­par­i­son de­sign, or SPCD. In an SPCD study, the first round of place­bo pa­tients who don’t re­spond to the drug are re-ran­dom­ized be­tween the drug arm and the sug­ar pill, in or­der to quell the high place­bo re­spons­es that have scut­tled nu­mer­ous oth­er tri­als for de­pres­sion.

What are Alk­er­mes’ chances of chang­ing the FDA’s de­ci­sion? Not good. Top of­fi­cials are well es­tab­lished, of­fer­ing re­peat­ed sig­nals that they’re will­ing to be flex­i­ble on the da­ta when need­ed. If this drug failed to get past Janet Wood­cock as well as FDA com­mis­sion­er Scott Got­tlieb, af­ter the FDA re­versed three oth­er re­jec­tions ear­ly in Got­tlieb’s tenure at the agency, it’s un­like­ly cir­cum­stances will change now.

The RTF no­tice is a par­tic­u­lar­ly harsh blow for Pops, who’s been in­sist­ing to in­vestors that the com­pa­ny would get this past reg­u­la­tors and on­to the mar­ket. Fail­ing to even get past the ini­tial re­view and have the ap­pli­ca­tion spurned at the door will not sit well with com­pa­ny back­ers.


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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The home run count: The $100M+ mega-round boom in biotech in­spired a $6.7B feed­ing fren­zy — so far this year

Over the last 6 months there’s been a blizzard of money piling up drifts of the green stuff through the biotech landscape. And the forecast calls for more cash windfalls ahead.

Even as a global pandemic has killed more than half a million people, blighted economies and divided nations over the proper response, it’s also helped ignite an unprecedented burst of big-time investing. And not just in Covid-19 deals, as we’ve looked at before.

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For­bion spot­lights late-stage plays, carves out new €250M growth fund

Having staked its rep on picking out a mix of biotech investment opportunities across the “build,” “enable,” “growth” continuum, Forbion is launching its first fund dedicated to late-stage opportunities.

Forbion Growth Opportunities Fund’s first close brought in €185 million ($208 million). Existing investors Pantheon, KfW Capital and the European Investment Fund came on board, joined by new backers Eli Lilly, Horizon Therapeutics, Belgian Growth Fund and New Waves Investments.

Mer­ck ex­pands scope of Zymeworks an­ti­body al­liance, adding close to $900M in mile­stones

Nearly a decade after first partnering with Merck, Vancouver-based biotech Zymeworks has expanded its collaboration with the pharma giant once again.

Zymeworks re-upped with Merck in a new licensing agreement, granting the New Jersey pharma giant the right to develop up to 3 additional multispecific antibody candidates. In exchange, the biotech will receive an undisclosed upfront payment — Merck is always loath to discuss cash terms — and nearly $900 million in combined regulatory ($411 million) and commercial ($480 million) milestones.

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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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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.

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

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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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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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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