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.

FDA chief Stephen Hahn on Capitol Hill earlier this week (Getty Images)

As FDA’s work­load buck­les un­der the strain, Trump again ac­cus­es the agency of a po­lit­i­cal hit job

Peter Marks appeared before a virtual SVB Leerink audience yesterday and said that his staff at FDA’s CBER is on the verge of working around the clock. Manufacturing inspections, policy work and sponsor communications have all been pushed down the to-do list so that they can be responsive to Covid-related interactions. And the agency’s objective right now? “To save as many lives as we can,” Marks said, likening the mortality on the current outbreak as equivalent to “a nuclear bomb on a small city.”

Mi­no­ryx and Sper­o­genix ink an ex­clu­sive li­cense agree­ment to de­vel­op and com­mer­cial­ize lerigli­ta­zone in Chi­na

September 23, 2020 – Hong Kong, Beijing, Shanghai (China) and Mataró, Barcelona (Spain)  

Minoryx will receive an upfront and milestone payments of up to $78 million, as well as double digit royalties on annual net sales 

Sperogenix will receive exclusive rights to develop and commercialize leriglitazone for the treatment of X-linked adrenoleukodystrophy (X-ALD), a rare life-threatening neurological condition

President Donald Trump reacts after signing an executive order following his remarks on his healthcare policies yesterday in Charlotte, North Carolina (Getty Images)

Op-ed: Will phar­ma re­al­ly pay for Trump’s lat­est law­less promise to 33 mil­lion Medicare ben­e­fi­cia­ries? Not like­ly

Sitting atop the executive branch, President Donald Trump is the ultimate authority at the FDA. He can fast track any vaccine to approval himself. If it came to that, of course.

What he can’t do is unilaterally order the legislative branch to loosen the Treasury’s coffers for $6.6 billion. Nor can he command pharmaceutical companies to pay for $200 vouchers sent to 33 million Medicare beneficiaries for prescription drugs before the election.

President Donald Trump and FDA Commissioner Stephen Hahn (AP Images)

FDA is­sues fi­nal rule al­low­ing im­por­ta­tion of drugs from Cana­da — but al­so keeps the pow­er to re­voke it

Just over a month away from the presidential election, the FDA has issued a final regulation fulfilling President Trump’s promise to let states import certain prescription drugs from Canada.

On Thursday, Trump told a crowd in North Carolina that the new rule goes into effect “today.” But the published regulation states that it won’t take effect for 60 days. And even then, it could be a while before cheaper drugs make it across the border.

The win­dow is wide open as four more biotechs join the go-go IPO class of 2020

It’s another day of hauling cash in the biopharma world as four more IPOs priced Friday and a fifth filed its initial paperwork.

The biggest offering comes from PMV Pharma, an oncology biotech focusing on p53 mutations, which raised $211.8 million after pricing shares at $18 apiece. Prelude Therapeutics, developing PRMT5 inhibitors for rare cancers, was next with a $158 million raise, pricing shares at $19 each. Graybug Vision raised $90 million after pricing at $16 per share for its wet AMD candidates, and breast cancer biotech Greenwich Lifesciences brought up the rear with a small, $7 million raise after pricing shares at $5.75.

J&J of­fers PhI/IIa da­ta show­ing its sin­gle-dose vac­cine can stir up suf­fi­cient im­mune re­sponse

Days after J&J dosed the first participants of its Phase III ENSEMBLE trial, the pharma giant has detailed the early-stage data that gave them confidence in a single-dose regimen.

Testing two dose levels either as a single dose or in a two-dose schedule spaced by 56 days in, the scientists from Janssen, the J&J subsidiary developing its vaccine, reported that the low dose induced a similar immune response as the high dose. The interim Phase I/IIa results were posted in a preprint on medRxiv.

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

Play-by-play of Gilead­'s $21B Im­munomedics buy­out de­tails a fren­zied push — and mints a new biotech bil­lion­aire

Immunomedics had not really been looking for a buyout when the year began. Excited by its BLA for Trodelvy, submitted to the FDA in late 2019, executive chairman Behzad Aghazadeh started off looking for potential licensing deals and zeroed in on four potential partners, including Gilead, following January’s JP Morgan Healthcare Conference in San Francisco. Such talks advanced throughout the year, with discussions advancing to the second round in mid-August.

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New York governor Andrew Cuomo (AP Images)

An­drew Cuo­mo says New York will un­der­take its own vac­cine re­view process, and wouldn’t rec­om­mend trust­ing the fed­er­al gov­ern­ment

The concerns keep mounting over President Donald Trump’s politicization of the FDA and other federal agencies guiding the development of a safe and effective vaccine. And today, the telegenic New York governor Andrew Cuomo appeared to introduce even more politics into the matter — latest in an ongoing series of incidents that have cast the proudly independent FDA in starkly political terms.

During his daily press conference Cuomo said that the state will review any coronavirus vaccines approved by the federal government, citing a lack of trust in the Trump administration. The announcement comes one day after Trump accused the FDA of making an “extremely political” move in proposing stricter vaccine guidance.

President Trump walks past HHS secretary Alex Azar (Getty Images)

Azar falls in line un­der Trump again. Ex­perts say he's re­in­forc­ing a dark sig­nal sent to the FDA

In the latest incident where Alex Azar has steadfastly taken the side of President Donald Trump over that of the FDA, the HHS secretary was noncommittal this morning when asked if he supports the attempt by his subordinates at the FDA to strengthen guidelines for a vaccine EUA.

Appearing on NBC’s Today Show, the HHS secretary muddied the waters, stating that the guidance that matters is the one that is “actually already out there.”