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)

The FDA will hus­tle up an ac­cel­er­at­ed re­view for As­traZeneca’s next shot at a block­buster can­cer drug fran­chise

AstraZeneca paid a hefty price to partner with Daiichi Sankyo on their experimental antibody drug conjugate for HER2 positive breast cancer. And they’ve been rewarded with a fast ride through the FDA, with a straight shot at creating another blockbuster oncology franchise.

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Sean Parker, AP

Sean Park­er helps cre­ate a CRISPRed cell ther­a­py 2.0 play — and he’s got a high-pro­file set of lead­ers on the team

You can rack up one more high-profile debut effort in the wave of activity forming around cell therapy 2.0. It’s another appealing Bay Area group that’s attracted some of the top hands in the business to a multi-year effort to create a breakthrough. And they have $85 million in hand to make that first big step to the clinic.

Today it’s Ken Drazan and the team at South San Francisco-based ArsenalBio that are coming from behind the curtain for a public bow, backed by billionaire Sean Parker and a collection of investors that includes Beth Seidenberg’s new venture investment operation based in LA.
Drazan — a J&J Innovation vet with a long record of entrepreneurial endeavors — exited the stage in 2018 when his last mission ended as he stepped aside as president of Grail. It wasn’t long, though, before he was helping out with a business plan for ArsenalBio that revolved around the work of a large group of interconnected scientists supported by the Parker Institute for Cancer Immunology.
The biotech started by putting together an “arsenal” of technologies aimed at making cell therapies for cancer much, much better than the rather crude first-generation drugs that hit the market from Novartis and Kite.
Their drugs have become the baseline against which all others are being measured.
“The technology set we’re developing is independent of the chassis,” Drazan tells me. “It doesn’t have to be autologous (extracted from the patient) or allogeneic (off the shelf). It doesn’t have to be a T cell, it could be a B cell.” But they are starting out on the autologous side, where they have the most knowledge and insight into manufacturing techniques.
It also doesn’t have to be close to the clinic.
Drazan expects the biotech will be working its way through preclinical operations for “a few years,” with enough money from the $85 million launch round to get into humans.
By today’s superheated fundraising standards, that’s not a huge amount of cash. Lyell, another cell therapy 2.0 startup we featured last week, raised $600 million in a year, including a big chunk of cash from GlaxoSmithKline. Drazan is interested in dealmaking as well, but he also knows he has the cash necessary to support the company for a good run — a key part of what it takes to bring together a stellar team of top players.

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Eli Lil­ly’s first PhI­II show­down for their $1.6B can­cer drug just flopped — what now?

When Eli Lilly plunked down $1.6 billion in cash to acquire Armo Biosciences a little more than a year ago, the stars seemed aligned in its favor. The jewel in the crown they were buying was pegilodecakin, which had cleared the proof-of-concept stage and was already in a Phase III trial for pancreatic cancer.

And that study just failed.

Lilly reported this morning that their cancer drug flopped on overall survival when added to FOLFOX (folinic acid, 5-FU, oxaliplatin), compared to FOLFOX alone among patients suffering from advanced pancreatic cancer.

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Swamy Vijayan. Plexium

San Diego up­start de­buts dis­cov­ery en­gine that puts a twist to pro­tein degra­da­tion

For years, the idea of protein degradation — utilizing the cell’s natural garbage disposal system to mark problematic proteins for destruction — remained an elegant but technically difficult concept. But now established as a promising clinical strategy, with major biopharma players such as Bayer, Gilead and Vertex trying to grab a foothold via partnership deals, a San Diego startup is looking to exploit it and push its limits.

CSL ac­cus­es ri­val Pharm­ing of par­tic­i­pat­ing in a scheme to rip off IP on HAE while re­cruit­ing se­nior R&D staffer

Pharming has landed in the middle of a legal donnybrook after recruiting a senior executive from a rival R&D team at CSL. The Australian pharma giant slapped Pharming with a lawsuit alleging that the Dutch biotech’s new employee, Joseph Chiao, looted a large cache of proprietary documents as he hit the exit. And they want it all back.
Federal Judge Juan Sanchez in the Eastern District Pennsylvania court issued an injunction on Tuesday prohibiting Chiao from doing any work on HAE or primary immune deficiency in his new job and demanding that he return any material from CSL that he may have in his possession. And he wants Pharming to tell its employees not to ask for any information on the forbidden topics.
For its part, Pharming fired off an indignant response this morning denying any involvement in extracting any kind of IP from CSL, adding that it’s cooperating in the internal probe that CSL has underway.

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Hal Barron, GSK's president of R&D and CSO, speaks to Endpoints News founder and editor John Carroll in London at Endpoints' #UKBIO19 summit on October 8, 2019

[Video] Cel­e­brat­ing tri­al fail­ures, chang­ing the cul­ture and al­ly­ing with Cal­i­for­nia dream­ers: R&D chief Hal Bar­ron talks about a new era at GSK

Last week I had a chance to sit down with Hal Barron at Endpoints’ #UKBIO19 summit to discuss his views on R&D at GSK, a topic that has been central to his life since he took the top research post close to 2 years ago. During the conversation, Barron talked about changing the culture at GSK, a move that involves several new approaches — one of which involves celebrating their setbacks as they shift resources to the most promising programs in the pipeline. Barron also discussed his new alliances in the Bay Area — including his collaboration pact with Lyell, which we covered here — frankly assesses the pluses and minuses of the UK drug development scene, and talks about his plans for making GSK a much more effective drug developer.

This is one discussion you won’t want to miss. Insider and Enterprise subscribers can log-in to watch the video.

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Med­ical an­i­ma­tion: Mak­ing it eas­i­er for the site and the pa­tient to un­der­stand

Medical animation has in recent years become an increasingly important tool for conveying niche information to a varied audience, particularly to those audiences without expertise in the specialist area. Science programmes today, for example, have moved from the piece-to-camera of the university professor explaining how a complex disease mechanism works, to actually showing the viewer first-hand what it might look like to shrink ourselves down to the size of an ant’s foot, and travel inside the human body to witness these processes in action. Effectively communicating a complex disease pathophysiology, or the novel mechanism of action of a new drug, can be complex. This is especially difficult when the audience domain knowledge is limited or non-existent. Medical animation can help with this communication challenge in several ways.
Improved accessibility to visualisation
Visualisation is a core component of our ability to understand a concept. Ask 10 people to visualise an apple, and each will come up with a slightly different image, some apples smaller than others, some more round, some with bites taken. Acceptable, you say, we can move on to the next part of the story. Now ask 10 people to visualise how HIV’s capsid protein gets arranged into the hexamers and pentamers that form the viral capsid that holds HIV’s genetic material. This request may pose a challenge even to someone with some virology knowledge, and it is that inability to effectively visualise what is going on that holds us back from fully understanding the rest of the story. So how does medical animation help us to overcome this visualisation challenge?

UP­DAT­ED: Alex­ion pays $930M to buy out Achillion and its promis­ing com­pan­ion drug to Soliris

After a series of stock-crunching setbacks over the years, Achillion enjoyed a turn in the sun a few weeks ago as the FDA blessed their lead drug danicopan (ACH-4471) — a complementary therapy for PNH patients taking Alexion’s Soliris — with a breakthrough drug designation after taking a look at some solid supporting Phase II data.

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The $102B club: The top 15 R&D spenders in the glob­al bio­phar­ma busi­ness — 2019 edi­tion

Over the past few years, the deluge of capital into biotech has helped lead to a dramatic shift in focus on new drug approvals, as startups are now able to raise enough cash to get through a pivotal and onto the market. But the top 15 players still account for $102 billion in spending, and their successes and failures continue to determine just how productive the industry is.

Recently we’ve seen a number of new R&D chiefs take their places at the Big 15, either setting the stage for a more focused R&D strategy — often playing more heavily in oncology. That’s true for AstraZeneca, which has had some landmark successes, and GSK, which is in search of its own turnaround in pharma R&D. HIV and vaccines are separate from that group, now led by Hal Barron.

I’ve made a point of watching their track record every year for more than a decade now. What follows is intended as a broad gauge of their activity. You don’t have to have a lot of major successes to score a winning record here, but it’s virtually impossible without a blockbuster or three in the pipeline.

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