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)

Brian Kaspar. AveXis via Twitter

AveX­is sci­en­tif­ic founder fires back at No­var­tis CEO Vas Narasimhan, 'cat­e­gor­i­cal­ly de­nies any wrong­do­ing'

Brian Kaspar’s head was among the first to roll at Novartis after company execs became aware of the fact that manipulated data had been included in its application for Zolgensma, now the world’s most expensive therapy.

But in his first public response, the scientific founder at AveXis — acquired by Novartis for $8.7 billion — is firing back. And he says that not only was he not involved in any wrongdoing, he’s ready to defend his name as needed.

I reached out to Brian Kaspar after Novartis put out word that he and his brother Allen had been axed in mid-May, two months after the company became aware of the allegations related to manipulated data. His response came back through his attorneys.

Endpoints News

Basic subscription required

Unlock this story instantly and join 57,900+ biopharma pros reading Endpoints daily — and it's free.

UP­DAT­ED: An em­bold­ened As­traZeneca splurges $95M on a pri­or­i­ty re­view vouch­er. Where do they need the FDA to hus­tle up?

AstraZeneca is in a hurry.

We learned this morning that the pharma giant — not known as a big spender, until recently — forked over $95 million to get its hands on a priority review voucher from Sobi, otherwise known as Swedish Orphan Biovitrum.

That marks another step down on price for a PRV, which allows the holder to slash 4 months off of any FDA review time.

Endpoints News

Basic subscription required

Unlock this story instantly and join 57,900+ biopharma pros reading Endpoints daily — and it's free.

Martin Shkreli [via Getty]

Pris­on­er #87850-053 does not get to add drug de­vel­op­er to his list of cred­its

Just days after Retrophin shed its last ties to founder Martin Shkreli, the biotech is reporting that the lead drug he co-invented flopped in a pivotal trial. Fosmetpantotenate flunked both the primary and key secondary endpoints in a placebo-controlled trial for a rare disease called pantothenate kinase-associated neurodegeneration, or PKAN.

Endpoints News

Basic subscription required

Unlock this story instantly and join 57,900+ biopharma pros reading Endpoints daily — and it's free.

We­bi­nar: Re­al World End­points — the brave new world com­ing in build­ing fran­chise ther­a­pies

Several biopharma companies have been working on expanding drug labels through the use of real world endpoints, combing through the data to find evidence of a drug’s efficacy for particular indications. But we’ve just begun. Real World Evidence is becoming an important part of every clinical development plan, in the soup-through-nuts approach used in building franchises.

I’ve recruited a panel of 3 top experts in the field — the first in a series of premium webinars — to look at the practical realities governing what can be done today, and where this is headed over the next few years, at the prodding of the FDA.

ZHEN SU — Merck Serono’s Senior Vice President and Global Head of Oncology
ELLIOTT LEVY — Amgen’s Senior Vice President of Global Development
CHRIS BOSHOFF — Pfizer Oncology’s Chief Development Officer

A premium subscription to Endpoints News is required to attend this webinar. Please upgrade to either an Insider or Enterprise plan for access. Already have Endpoints Premium? Please sign-in below. You can contact our Subscriptions team at help@endpointsnews.com with any issues.

Endpoints Premium

Premium subscription required

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

Am­gen, Al­ler­gan biosim­i­lar of Roche's block­buster Rit­ux­an clears an­oth­er US piv­otal study 

Novartis $NVS may have given up, but Amgen $AMGN and Allergan $AGN are plowing ahead with their knockoff of Roche’s blockbuster biologic Rituxan in the United States.

Their copycat, ABP 798, was found to have a clinically equivalent impact as Rituxan — meeting the main goal of the study involving CD20-positive B-cell non-Hodgkin’s lymphoma patients. This is the second trial supporting the profile of the biosimilar. In January, it came through with positive PK results in patients with rheumatoid arthritis.

BeiGene and Mus­tang nail down spe­cial FDA sta­tus for top drugs; Roche bags added cov­er­age for Hem­li­bra

→ BeiGene $BGNE is getting a boost in its drive to field a rival to Imbruvica. The FDA has offered an accelerated review to zanubrutinib, a BTK inhibitor that has posted positive results for mantle cell lymphoma. The PDUFA date lands on February 27, 2020. The drug scored breakthrough status at the beginning of the year.

→ BeiGene isn’t the only biopharma company to gain special regulatory status today. Mustang Bio $MBIO and St. Jude Children’s Research Hospital announced that MB-107, a lentiviral gene therapy for the treatment of X-linked severe combined immunodeficiency, also known as bubble boy disease, has been granted Regenerative Medicine Advanced Therapy status.

Trump ad­min­is­tra­tion re­vives bid to get drug list prices on TV ads

The Trump administration is not giving up just yet. On Wednesday, the HHS filed an appeal against a judge’s decision in July to overturn a ruling obligating drug manufacturers to disclose the list price of their therapies in television adverts — hours before it was stipulated to go into effect.

In May, the HHS published a final ruling requiring drugmakers to divulge the wholesale acquisition cost— of a 30-day supply of the drug — in tv ads in a bid to enhance price transparency in the United States. The pharmaceutical industry has vehemently opposed the rule, asserting that list prices are not what a typical patient in the United States pays for treatment — that number is typically determined by the type of (or lack thereof) insurance coverage, deductibles and out-of-pocket costs. Although there is truth to that claim, the move was considered symbolic in the Trump administration’s healthcare agenda to hold drugmakers accountable in a climate where skyrocketing drug prices have incensed Americans on both sides of the aisle.

Ver­sant-backed Chi­nook gets a $65M launch round for its dis­cov­ery quest in a resur­gent kid­ney field

Versant is once again stepping off the beaten track in biotech to see if they can blaze a trail of their own in a field that has looked too thorny to many investors for years.

The venture group and their partners at Apple Tree are bringing their latest creation out of stealth mode today. Born in Versant’s Inception Sciences’ Chinook Therapeutics is betting that its preclinical take on kidney disease can get an early lead among the companies starting up in the field.

Sir An­drew Dil­lon, NICE's first — and on­ly — chief ex­ec­u­tive to step down next year

Using a laptop borrowed from his former employer, South London’s St George’s Hospital, Sir Andrew Dillon set about establishing NICE — launched by the then health secretary Frank Dobson — in 1999.  On Thursday, the UK cost-effectiveness watchdog said its first and only chief executive — Dillon — is stepping down in March 2020.

Back in the day, decisions about which drugs and interventions were funded by the National Health Service (NHS) were made at the local level, but this ‘postcode prescribing’ system was fraught with skewed healthcare deployment making the structure unsustainable. A national system was deemed necessary — and NICE was formed to bridge that gap.