FDA staff large­ly un­fazed by CV sig­nal in Am­gen os­teo­poro­sis drug tri­als

FDA staff braved the snow and the fed­er­al shut­down to post their re­view of Am­gen’s once-re­ject­ed os­teo­poro­sis drug on Mon­day, un­der­scor­ing that the ef­fi­ca­cy of the drug in post­menopausal women had been es­tab­lished, and sug­gest­ing that the CV sig­nal ob­served in two tri­als may not be a sig­nif­i­cant wor­ry.

The re­view comes days af­ter Am­gen and part­ner UCB se­cured Japan­ese ap­proval for the drug, ro­mosozum­ab, and pre­cedes a meet­ing of in­de­pen­dent ex­perts on Wednes­day who will make their rec­om­men­da­tion on the ap­prov­abil­i­ty of the drug in the Unit­ed States. Ro­mosozum­ab — which is to be sold un­der the brand name Eveni­ty — func­tions pre­dom­i­nant­ly as a bone an­a­bol­ic agent that stim­u­lates bone growth.

The mon­o­clon­al an­ti­body was test­ed in three late-stage stud­ies: the 7,180-pa­tient FRAME study in post­menopausal women with os­teo­poro­sis, which test­ed the drug against a place­bo; the 4,093-pa­tient ARCH study in post­menopausal women in os­teo­poro­sis, which test­ed the drug against an os­teo­poro­sis drug orig­i­nal­ly made by Mer­ck called al­en­dronate; and the 245-pa­tient BRIDGE study in men with os­teo­poro­sis, which test­ed the drug against a place­bo.

All three piv­otal stud­ies showed the drug was ef­fec­tive, but the ARCH and BRIDGE tri­al demon­strat­ed a sig­nal of car­dio­vas­cu­lar-re­lat­ed se­ri­ous ad­verse events, which led to the FDA is­su­ing a com­plete re­sponse let­ter to the com­pa­nies, af­ter they had ap­plied for ap­proval in post­menopausal women with os­teo­poro­sis. Tak­ing in­to ac­count the CV sig­nal and feed­back from the FDA about the pauci­ty of an­a­bol­ic agents, the duo re-sub­mit­ted an ap­pli­ca­tion to mar­ket drug last year, but for a nar­row­er pa­tient pop­u­la­tion: post­menopausal women with os­teo­poro­sis who car­ry a high risk of frac­ture. They al­so pro­posed a boxed warn­ing as well as a pre­cau­tion for car­dio­vas­cu­lar risk on the drug’s la­bel, if ap­proved. Mean­while, the drug is un­der re­view in Eu­rope.

Glob­al­ly, 1 in 3 women over age 50 will ex­pe­ri­ence os­teo­porot­ic frac­tures, ac­cord­ing to the In­ter­na­tion­al Os­teo­poro­sis Foun­da­tion.

In its re­view, FDA staff agreed that the ef­fec­tive­ness of ro­mosozum­ab for the treat­ment of post­menopausal os­teo­poro­sis had been es­tab­lished, but ques­tioned whether the CV sig­nal seen in ARCH and BRIDGE were gen­er­al­iz­able to the US pop­u­la­tion, giv­en that en­rolled pa­tients from the US on­ly ac­count­ed for 1.8% of the ARCH study, and 1.4% of the BRIDGE study. In their sug­gest­ed ques­tions for in­de­pen­dent pan­el, the agency’s re­view­ers did not stress the CV is­sue.

“The docs read most­ly be­nign and dis­cus­sion/vot­ing ques­tions are not as crit­i­cal on CV risk, sup­port­ing a fa­vor­able pan­el vote on Wed (1/16) and an even­tu­al ap­proval lat­er in H1:19,” Jef­feries an­a­lysts wrote in a note, adding that Lil­ly’s os­teo­poro­sis drug For­teo car­ries a black box warn­ing high­light­ing the risk of can­cer and still rakes in about $2 bil­lion.

The drug “rep­re­sents a mod­est $500 mil­lion world­wide up­side op­por­tu­ni­ty not wide­ly ac­count­ed by con­sen­sus, and the drug has shown strong ef­fi­ca­cy (beat­ing Fos­amax by 48-50%) along with an ac­cept­able safe­ty pro­file. The pri­or safe­ty sig­nal seen in the small­er of two key Phase III stud­ies (ARCH vs FRAME) seems more spu­ri­ous than con­cern­ing to us,” they not­ed.

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.

Endpoints Premium

Premium subscription required

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

Shoshanna Shendelman, Applied Therapeutics CEO (Applied Therapeutics)

A lit­tle biotech slaps back at a 'crim­i­nal' short at­tack, vow­ing to pur­sue a pros­e­cu­tion of their case

As short attacks go, Biotech Research Partners’ assault on Applied Therapeutics’ “cherry picked” data and a variety of so-called red flags didn’t cause a whole lot of damage. Ahead of the July 4 holiday, its shares $APLT were dinged and showed signs of quick recovery.

But that didn’t stop an incendiary response, as the biotech swung into action bright and early Monday morning.

Applied Therapeutics accused the authors of the short report of manipulating graphs and figures, misrepresenting data and included factual misrepresentations — all of which added up, in their view, to fraud.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 84,700+ biopharma pros reading Endpoints daily — and it's free.

Cel­lec­tis slammed af­ter pa­tient dies and FDA slaps a hold on their tri­al for an off-the-shelf CAR-T for mul­ti­ple myelo­ma

Cellectis was slammed after the market close on Monday as the biotech reported that the FDA demanded it hit the brakes on their MELANI-01 trial for their off-the-shelf cell therapy UCARTCS1A after one of the patients in the study died of treatment-related cardiac arrest.

The multiple myeloma patient had previously been treated unsuccessfully with various therapies, noted the biotech, and had been given dose level two (DL2) of their allogeneic CAR-T.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 84,700+ biopharma pros reading Endpoints daily — and it's free.

UP­DAT­ED: Im­munomedics spells out PFS ben­e­fit of Trodelvy in mTNBC, hunt­ing a full OK just weeks af­ter ac­cel­er­at­ed ap­proval

By the time the FDA finally granted an accelerated OK for Immunomedics’ Trodelvy, we already got a very strong hint that their confirmatory Phase III study in metastatic triple-negative breast cancer was a success.

That’s because the independent data safety monitoring committee recommended that the trial be stopped early. But just what pointed them to the conclusion was still unclear.

“We do not know the totality of their decision other than it’s pretty evident that the primary endpoint was met; otherwise they could not request to halt the study,” Behzad Aghazadeh, the executive chairman, told Endpoints News at the time.

Bill Haney, Dragonfly CEO (Dave Pedley/Getty Images for SXSW)

A boom­ing Drag­on­fly is tak­ing its TriN­KETs to Copen­hagen as the lat­est Bris­tol My­ers pact spurs ex­pan­sion plans — out­side the US

Bristol Myers Squibb is making a habit out of collaborating with the crew at Dragonfly, adding their 3rd deal in a series that now will take them into newly charted R&D territory. And the fast-growing team at the Cambridge-based biotech is adding a facility in Copenhagen for its next growth spurt, where the government is making it easy to recruit scientists internationally as the U.S. throttles back.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 84,700+ biopharma pros reading Endpoints daily — and it's free.

Covid-19 roundup: Teamed up with NIH, Re­gen­eron launch­es PhI­II pre­ven­tion tri­al for an­ti­body cock­tail

As Regeneron moves its antibody cocktail into Phase II/III trials testing REGN-COV2 as a treatment for both hospitalized and non-hospitalized patients with Covid-19, the biotech is also starting a Phase III in the prevention setting.

The National Institute of Allergy and Infectious Diseases — which orchestrated the large, randomized study for remdesivir that produced positive results — will jointly run the study.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 84,700+ biopharma pros reading Endpoints daily — and it's free.

Douglas Love, Annexon CEO (Annexon)

IPO bound? Ac­tu­al­ly, An­nex­on was al­ready prepped and primed to toss its S-1 to Wall Street as in­vestors ral­lied

The Wall Street IPO shuffle generally calls for a little distance between the crossover ante and the Wall Street double, but with the window on the street wide open and biotech sizzling hot, who’s waiting?

The crew at Annexon didn’t leave anyone in suspense for long about their IPO plans. A day after the Bay Area biotech with clinical plans to target neurodegeneration quietly unveiled a $100 million raise, they were back with an S-1 outlining a pitch to double that — or more.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 84,700+ biopharma pros reading Endpoints daily — and it's free.

Jean-Paul Clozel, Idorsia CEO (Patrick Straub/Keystone via AP Images)

Sec­ond PhI­II study for Idor­si­a's sleep drug re­turns pos­i­tive re­sults, but al­so rais­es new ques­tions

Following a successful Phase III study in April showcasing the safety and potential of its new sleep drug, Idorsia posted some mixed news in the second Phase III study, but that won’t stop a planned filing aimed at regulatory approval.

The drug, a dual orexin receptor antagonist (DORA) called daridorexant, was found to significantly improve sleep maintenance and subjective total sleep time in 25 mg doses, replicating results from the first Phase III study. However, improvements in sleep onset and daytime functioning narrowly missed statistical significance, despite numerical consistency with the April study.

Elias Zerhouni (Photo by Vincent Isore/IP3/Getty Images)

Elias Zer­houni dis­cuss­es ‘am­a­teur hour’ in DC, the de­struc­tion of in­fec­tious dis­ease R&D and how we need to prep for the next time

Elias Zerhouni favors blunt talk, and in a recent discussion with NPR, the ex-Sanofi R&D and ex-NIH chief had some tough points to make regarding the pandemic response.

Rather than interpret them, I thought it would be best to provide snippets straight from the interview.

On the Trump administration response:

It was basically amateur hour. There is no central concept of operations for preparedness, for pandemics, period. This administration doesn’t want to or has no concept of what it takes to protect the American people and the world because it is codependent. You can’t close your borders and say, “OK, we’re going to be safe.” You’re not going to be able to do that in this world. So it’s a lack of vision, basically just a lack of understanding, of what it takes to protect the American people.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 84,700+ biopharma pros reading Endpoints daily — and it's free.