Once spurned, Am­gen wins the FDA over with its bone-build­ing os­teo­poro­sis drug Eveni­ty

El­liott Levy (Am­gen)

As ex­pect­ed, Am­gen’s once-re­ject­ed os­teo­poro­sis drug has scored FDA ap­proval, paving the way for a new bone-build­ing op­tion for the one in two post­menopausal women in the Unit­ed States whose weak­ened bones make them high­ly sus­cep­ti­ble to frac­tur­ing.

Ro­mosozum­ab is to be sold un­der the brand name Eveni­ty. It func­tions pre­dom­i­nant­ly as a bone an­a­bol­ic agent that stim­u­lates bone growth by in­hibit­ing a pro­tein called scle­rostin, which ceas­es the pro­duc­tion of bone and en­hances its break­down. The cur­rent stan­dard of care for the 10 mil­lion Amer­i­cans with os­teo­poro­sis is a fam­i­ly of drugs called bis­pho­s­pho­nates — such as al­en­dronate (orig­i­nal­ly sold un­der the brand name Fos­amax by Mer­ck) — that thwart cells called os­teo­clasts that break down bone tis­sue but do not re­build it.

In the US, one in two women over the age of 50 will ex­pe­ri­ence an os­teo­porot­ic frac­ture — an in­ci­dence that sur­pass­es that of heart at­tack, stroke and breast can­cer com­bined, ac­cord­ing to the Na­tion­al Os­teo­poro­sis Foun­da­tion, which es­ti­mates os­teo­poro­sis will be re­spon­si­ble for three mil­lion frac­tures re­sult­ing in $25.3 bil­lion in costs by 2025.

Eveni­ty was test­ed in three late-stage stud­ies: the 7,180-pa­tient place­bo-con­trolled FRAME study in post­menopausal women with os­teo­poro­sis; the 4,093-pa­tient ARCH study in post­menopausal women in os­teo­poro­sis, which test­ed the drug against al­en­dronate; and the 245-pa­tient place­bo-con­trolled BRIDGE study in men with os­teo­poro­sis. All three piv­otal stud­ies showed the mon­o­clon­al an­ti­body was ef­fec­tive, but se­ri­ous CV ad­verse events were ob­served in the ARCH tri­al, which prompt­ed the FDA to orig­i­nal­ly is­sue a com­plete re­sponse let­ter to de­ny ap­proval in post­menopausal women with os­teo­poro­sis.

Tak­ing in­to ac­count the CV sig­nal and feed­back from the FDA about the pauci­ty of an­a­bol­ic agents, Am­gen and Bel­gian part­ner UCB 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, or pa­tients who have failed or are in­tol­er­ant to ex­ist­ing os­teo­poro­sis ther­a­pies.

In an out­side meet­ing of ex­perts to the FDA in Jan­u­ary, pan­elists large­ly backed the drug, de­spite the CV con­cerns. The FDA ac­knowl­edged the CV is­sue in Eveni­ty’s la­bel by high­light­ing that the use of the drug may in­crease the risk of heart at­tack, stroke and car­dio­vas­cu­lar death in a black box warn­ing, and asked the man­u­fac­tur­ers to con­duct a post-mar­ket­ing five-year ob­ser­va­tion­al fea­si­bil­i­ty study.

“There is no doubt that Eveni­ty is the most po­tent an­a­bol­ic agent for bone, but is al­so like­ly to see rel­a­tive­ly lim­it­ed use giv­en a tar­get pop­u­la­tion with sig­nif­i­cant un­der­ly­ing risk for such CV events al­ready,” SVB Leerink’s Ge­of­frey Porges said.

Even with the lim­it­ed use of the drug in con­text of the CV risk, Eveni­ty rep­re­sents a more than $500 mil­lion world­wide op­por­tu­ni­ty, Jef­feries an­a­lyst Michael Yee said, not­ing that Lil­ly’s os­teo­poro­sis drug For­teo car­ries a black box warn­ing high­light­ing the risk of can­cer and has been rak­ing in $1.5+ bil­lion in the last two years.

“Al­though Eveni­ty showed greater bone min­er­al den­si­ty im­prove­ments than For­teo, we be­lieve the black box warn­ing for CV risk will lim­it up­take to the high­est-risk pa­tients with mul­ti­ple pri­or frac­tures,” BMO Cap­i­tal Mar­kets an­a­lyst Do Kim wrote in a note, ex­plain­ing that al­though For­teo and Tym­los (an­oth­er bone an­a­bol­ic agent, sold by Ra­dius Health) car­ry black box warn­ings for os­teosar­co­ma, the find­ings were in an­i­mal stud­ies and not ver­i­fied in hu­mans.

“Both For­teo and Tym­los re­quire dai­ly dos­ing, com­pared to Eveni­ty’s once-month­ly. We could see pref­er­ence for Eveni­ty in pa­tients with­out pri­or CV events, giv­en less fre­quent dos­ing and as­sum­ing a low­er price,” Kim said.

Al­though Eveni­ty’s la­bel re­flects its su­pe­ri­or bone-build­ing ef­fect, clin­i­cal da­ta showed the treat­ment did not trans­late in­to re­duced frac­ture risk for non-ver­te­bral frac­tures (e.g., hip and wrist frac­tures) which are the most con­se­quen­tial com­pli­ca­tions of os­teo­poro­sis, Porges point­ed out. “Tym­los and For­teo had a sig­nif­i­cant rel­a­tive risk re­duc­tion for non-ver­te­bral frac­tures of 43-53%, while Eveni­ty had a non-sig­nif­i­cant re­duc­tion of 25%.”

Pro­lia, Am­gen’s $AMGN 2018-ap­proved os­teo­poro­sis treat­ment is in­tend­ed for chron­ic treat­ment, as it works by in­creas­ing bone mass for as long as the pa­tient re­ceives it. Eveni­ty is in­tend­ed for short term use —  12 months — to rapid­ly in­crease bone min­er­al den­si­ty and re­duce frac­ture risk in pa­tients with im­mi­nent risk of frac­ture, it is then fol­lowed by an an­tire­sorp­tive agent such as Pro­lia, said El­liott Levy, Am­gen’s se­nior VP of glob­al de­vel­op­ment, in an in­ter­view with End­points News ahead of the FDA de­ci­sion.

In post­menopausal os­teo­poro­sis, bone re­sorp­tion ex­ceeds bone for­ma­tion, and an­tire­sorp­tive agents can help re­store skele­tal bal­ance by re­duc­ing bone turnover, pri­mar­i­ly at the tis­sue lev­el.

There are oth­er ef­fec­tive os­teo­poro­sis ther­a­pies avail­able, Levy said. “But they all take time to work and Eveni­ty, when giv­en for a year, works much more quick­ly, re­duces frac­ture risk much more quick­ly, and then it ap­pears to es­sen­tial­ly re­set frac­ture risk at a low­er lev­el, so when its fol­lowed by an an­tire­sorp­tive agent the risk of frac­ture is low­er than if the pa­tient had not re­ceived Eveni­ty.”

Eveni­ty will launch a week from now, at which point its price will be dis­closed, Am­gen said in a sep­a­rate re­lease on Tues­day.

“Eveni­ty will be priced at a dis­count to an­a­bol­ics, for bet­ter pay­er cov­er­age and to com­pete against pend­ing For­teo gener­ics,” BMO’s Kim sug­gest­ed, mod­el­ing an an­nu­al U.S. gross price of $7,200, well be­low For­teo’s $41,100 and Tym­los’s $21,900.

But the com­bi­na­tion of in­fe­ri­or non-ver­te­bral frac­ture risk re­duc­tion, and safe­ty and la­bel­ing li­a­bil­i­ties, sug­gest Eveni­ty’s adop­tion is like­ly to be mod­est, that Am­gen will un­like­ly pur­sue a price-based strat­e­gy, giv­en Tym­los’ al­ready ag­gres­sive pric­ing and the loom­ing in­tro­duc­tion of biosim­i­lar For­teo, Porges said.


Im­age: El­liott Levy (Am­gen)

In­vestors pony up $476M for the lat­est round of biotech IPOs to hit the Street

Three biotechs — and a genome se­quenc­ing play­er — have caught the lat­est tide to the Gold Coast of IPOs, round­ing out the first half of 2019 with 23 new drug de­vel­op­ers mak­ing it on Nas­daq.

Most of these com­pa­nies filed their IPOs al­most si­mul­ta­ne­ous­ly, though we’re still wait­ing on word of fel­low class­mate Bridge­Bio’s pric­ing af­ter CEO Neil Ku­mar set the terms at $14 to $16 a share on Mon­day in search of a $240 mil­lion (or so) wind­fall. If he’s suc­cess­ful, that would take the one-week haul past the $700 mil­lion mark, a fresh sign that in­vestors’ en­thu­si­asm for new­ly coined pub­lic biotechs hasn’t cooled.

In starved an­tibi­ot­ic field, Melin­ta soars as FDA grants speedy drug re­view

Such is the state of af­fairs in an­tibi­ot­ic land that the FDA agree­ing to pri­or­i­ty re­view an ap­pli­ca­tion to ex­pand the use of an an­tibi­ot­ic can rock­et up a stock more than two-fold.

On Wednes­day, Melin­ta Ther­a­peu­tics said its ap­proved an­tibi­ot­ic Baxdela had been grant­ed pri­or­i­ty re­view for use in com­mu­ni­ty-ac­quired bac­te­r­i­al pneu­mo­nia (CAPB). The FDA is ex­pect­ed to make its de­ci­sion by Oc­to­ber 24. Shares of the Con­necti­cut drug­mak­er $ML­NT cat­a­pult­ed, clos­ing up near­ly 224% at $6.41.

How small- to mid-sized biotechs can adopt pa­tient cen­tric­i­ty in their on­col­o­gy tri­als

By Lucy Clos­sick Thom­son, Se­nior Di­rec­tor of On­col­o­gy Pro­ject Man­age­ment, Icon

Clin­i­cal tri­als in on­col­o­gy can be cost­ly and chal­leng­ing to man­age. One fac­tor that could re­duce costs and re­duce bar­ri­ers is har­ness­ing the pa­tient voice in tri­al de­sign to help ac­cel­er­ate pa­tient en­roll­ment. Now is the time to adopt pa­tient-cen­tric strate­gies that not on­ly fo­cus on pa­tient needs, but al­so can main­tain cost ef­fi­cien­cy.

Robert Forrester, Verastem

Ve­rastem CEO For­rester steps to the ex­it as the board hunts com­mer­cial-savvy ex­ec for the be­lea­guered biotech

Robert For­rester is step­ping down as CEO of Ve­rastem On­col­o­gy $VSTM just 8 months af­ter the com­pa­ny nabbed an ap­proval for du­velis­ib, a PI3K drug with a sto­ried past — and what ap­pears as not much of a fu­ture.

The biotech put out word this morn­ing that For­rester will take an ad­vi­so­ry role with Ve­rastem while COO Dan Pa­ter­son steps up to take charge of the lead­er­ship team and the board looks around for a new CEO.

Brent Saunders at an Endpoints News event in 2017 — File photo

An­a­lyst call with Al­ler­gan ex­ecs stokes an­tic­i­pa­tion of a plan to split the com­pa­ny in ‘a month or two’

So what’s up at Al­ler­gan?

Ear­li­er this week the ubiq­ui­tous Ever­core ISI an­a­lyst Umer Raf­fat was on the line with com­pa­ny ex­ec­u­tives to probe in­to the lat­est on the num­bers as well as CEO Brent Saun­ders’ re­cent de­c­la­ra­tion that he’d be do­ing some­thing de­fin­i­tive to help long-suf­fer­ing in­vestors who have watched their shares dwin­dle in val­ue.

He came away with the im­pres­sion that a sig­nif­i­cant com­pa­ny split is on the way. And not on some dis­tant time hori­zon.

Ken Frazier appears before the Senate Committee on Finance for a hearing on prescription drug pricing on Capitol Hill in Washington, DC, February 26, 2019. Chris Kleponis for CNP via AP Images

Who’s next in line to suc­ceed Ken Fra­zier as CEO of the Keytru­da-blessed Mer­ck?

When Merck waved off a looming forced retirement for Ken Frazier last September, the board cited flexibility in CEO transition as a key factor in the decision. Having Frazier — who’s also chairman of the company — around beyond his 65th birthday in 2019 would ensure they install the best person at the best time, they said.

The board has evidently begun that process with a clear preference for internal candidates, sources told Bloomberg. CFO Robert Davis, chief marketing officer Michael Nally, and chief commercial officer Frank Clyburn are all in the running, according to an insider.

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John Reed at JPM 2019. Jeff Rumans for Endpoints News

Sanofi's John Reed con­tin­ues to re­or­ga­nize R&D, cut­ting 466 jobs while boost­ing can­cer, gene ther­a­py re­search

The R&D reorganization inside Sanofi is continuing, more than a year after the pharma giant brought in John Reed to head the research arm of the Paris-based company.
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UP­DAT­ED: Chica­go biotech ar­gues blue­bird, Third Rock 'killed' its ri­val, pi­o­neer­ing tha­lassemia gene ther­a­py in law­suit

Blue­bird bio $BLUE chief Nick Leschly court­ed con­tro­ver­sy last week when he re­vealed the com­pa­ny’s be­ta tha­lassemia treat­ment will car­ry a jaw-drop­ping $1.8 mil­lion price tag over a 5-year pe­ri­od in Eu­rope — mak­ing it the plan­et’s sec­ond most ex­pen­sive ther­a­py be­hind No­var­tis’ $NVS fresh­ly ap­proved spinal mus­cu­lar at­ro­phy ther­a­py, Zol­gens­ma, at $2.1 mil­lion. A Chica­go biotech, mean­while, has been fum­ing at the side­lines. In a law­suit filed ear­li­er this month, Er­rant Gene Ther­a­peu­tics al­leged that blue­bird and ven­ture cap­i­tal group Third Rock un­law­ful­ly prised a vi­ral vec­tor, de­vel­oped in part­ner­ship with the Memo­r­i­al Sloan Ket­ter­ing Can­cer Cen­ter (MSK), from its grasp, and thwart­ed the de­vel­op­ment of its sem­i­nal gene ther­a­py.

The top 10 block­buster drugs in the late-stage pipeline — Eval­u­ate adds 6 new ther­a­pies to heavy-hit­ter list

Vertex comes in for a substantial amount of criticism for its no-holds-barred tactical approach toward wresting the price it wants for its commercial drugs in Europe. But the flip side of that coin is a highly admired R&D and commercial operation that regularly wins kudos from analysts for their ability to engineer greater cash flow from the breakthrough drugs they create.

Both aspects needed for success in this business are on display in the program backing Vertex’s triple for cystic fibrosis. VX-659/VX-445 + Tezacaftor + Ivacaftor — it’s been whittled down to 445 now — was singled out by Evaluate Pharma as the late-stage therapy most likely to win the crown for drug sales in 5 years, with a projected peak revenue forecast of $4.3 billion.

The latest annual list, which you can see here in their latest world preview, includes a roster of some of the most closely watched development programs in biopharma. And Evaluate has added 6 must-watch experimental drugs to the top 10 as drugs fail or go on to a first approval. With apologies to the list maker, I revamped this to rank the top 10 by projected 2024 sales, instead of Evaluate's net present value rankings.

It's how we roll at Endpoints News.

Here is a quick summary of the rest of the top 10:

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