FDA re­jects Am­gen’s os­teo­poro­sis drug ro­mo as ri­val Ra­dius sur­pris­es with a new CEO

Af­ter miss­ing a key sec­ondary end­point for its big os­teo­poro­sis drug ro­mosozum­ab last fall and then run­ning in­to a dis­turb­ing safe­ty is­sue two months ago, Am­gen $AMGN said Sun­day that the FDA has hand­ed the big biotech a re­jec­tion on its mar­ket­ing ap­pli­ca­tion, a wide­ly an­tic­i­pat­ed set­back for the drug de­vel­op­er that will give ri­val Ra­dius a shot at es­tab­lish­ing a big lead in what had once been thought of as a horse race. And with­in hours of the CRL news from Am­gen, Ra­dius put out the word that it is mak­ing a change at the helm, with long­time CEO Bob Ward out and No­vo US pres­i­dent Jes­per Høi­land step­ping in to or­ches­trate the cam­paign for Ra­dius’ first mar­ket launch.

Jes­per Høi­land

Ac­cord­ing to the com­pa­ny’s state­ment, the agency says they want Am­gen to in­clude the da­ta from two late-stage stud­ies – the ARCH study as well as a Phase III in men called the BRIDGE tri­al, sig­nif­i­cant­ly de­lay­ing a come­back. That’s al­so bad news for UCB, which is part­nered with Am­gen.

BRIDGE was com­plet­ed more than a year ago. I asked a spokesper­son why the da­ta hadn’t al­ready been sup­plied to the FDA, and she said in re­ply that the ex­ec­u­tive crew at Am­gen would of­fer some added con­text dur­ing their earn­ings re­view Ju­ly 25.

In a fol­lowup on Mon­day af­ter­noon, Am­gen added: “Based on orig­i­nal dis­cus­sions with FDA, the FRAME study was suf­fi­cient for ini­tial BLA sub­mis­sion. The piv­otal 7,180-pa­tient FRAME tri­al was the first to eval­u­ate ver­te­bral frac­ture risk re­duc­tion as ear­ly as one year as a pri­ma­ry end­point.”

Ro­mo — which tar­gets the scle­rostin pro­tein — fol­lowed by Am­gen’s Pro­lia (deno­sum­ab) clear­ly vault­ed the bar in Phase III for re­duc­ing ver­te­bral frac­tures, with a hefty 75% risk re­duc­tion com­pared to a place­bo plus deno­sum­ab. In­ves­ti­ga­tors al­so were able to show a bet­ter safe­ty pro­file in its pre­sen­ta­tion at the an­nu­al con­fab of the Amer­i­can So­ci­ety for Bone Min­er­al Re­search. And there was an in­crease in bone min­er­al den­si­ty among the drug arm in the study.

But the drug al­so missed a key sec­ondary end­point in the piv­otal pro­gram. The drug did not sig­nif­i­cant­ly im­prove pa­tients’ risk of non-ver­te­bral frac­tures, leav­ing Ra­dius Health $RDUS with a pos­si­ble dis­tinct ad­van­tage on that score af­ter win­ning ap­proval in late April. Then in May, Am­gen pre­saged the re­jec­tion with a note spelling out a dis­turb­ing car­dio risk im­bal­ance be­tween ro­mo and Fos­amax; 2.5% for ro­mo and 1.9% for Fos­amax.

Reg­u­la­tors made it clear they want­ed to eval­u­ate the full set of da­ta in siz­ing up an ap­proval, de­rail­ing an ex­pect­ed sum­mer OK.

The board at Waltham, MA-based Ra­dius of­fered Ward a slap on the back and con­grat­u­la­tions for or­ga­niz­ing the IPO and Tym­los ap­proval. Chair­man Kurt Graves al­so made it clear that the com­pa­ny want­ed to go with an ex­pe­ri­enced hand at jump-start­ing new drug brands, giv­ing Høi­land a cheer for his work in that field at No­vo.

While both Am­gen and Ra­dius have an­gled for an ap­proval, com­mer­cial suc­cess is a com­plete­ly dif­fer­ent is­sue. As The New York Times re­port­ed re­cent­ly, pa­tients are gen­er­al­ly start­ed on bis­pho­s­pho­nates like Fos­amax, which are old and cheap. But they’re al­so lim­it­ed, un­able to build bone the way For­teo and the two new drugs are de­signed to do.

Lil­ly, mean­while, has been rapid­ly jack­ing up the price of For­teo ahead of its loss of patent pro­tec­tion. The Times re­ports the whole­sale price has soared to $3,100 a month, more than three times its price in 2010. Lil­ly has been in­creas­ing the price twice a year, for six years.

Sean Harp­er

Am­gen has had its ups and downs over the past year. Parsabiv was ap­proved ear­li­er this year, but isn’t ex­pect­ed to be­come a block­buster. A Phase III CGRP mi­graine drug – now part­nered with No­var­tis – has done well, but so have oth­er ri­val ther­a­pies that have been crowd­ing in. It’s had more suc­cess in the courts, but still faces an on­go­ing le­gal brawl with Re­gen­eron and Sanofi over the PC­SK9 mar­ket, while nei­ther group has been able to gain much trac­tion with pay­ers. Go­ing back to the draw­ing board on ro­mo won’t help, but can’t be avoid­ed as the drug faces an un­cer­tain fu­ture.

“Dur­ing our in­ter­ac­tions with the FDA, we agreed that the ARCH da­ta should be con­sid­ered in the reg­u­la­to­ry re­view pri­or to the ini­tial mar­ket­ing au­tho­riza­tion and, as a re­sult, an­tic­i­pat­ed this re­quest. We look for­ward to work­ing through the re­view process with the Agency,” said Sean Harp­er, ex­ec­u­tive vice pres­i­dent of R&D at Am­gen. “We re­main com­mit­ted to help­ing pa­tients with os­teo­poro­sis and will use the ad­di­tion­al time to bet­ter un­der­stand the ben­e­fit:risk pro­file of Eveni­ty.”

UP­DAT­ED: FDA’s golodirsen CRL: Sarep­ta’s Duchenne drugs are dan­ger­ous to pa­tients, of­fer­ing on­ly a small ben­e­fit. And where's that con­fir­ma­to­ry tri­al?

Back last summer, Sarepta CEO Doug Ingram told Duchenne MD families and investors that the FDA’s shock rejection of their second Duchenne MD drug golodirsen was due to some concerns regulators raised about the risk of infection and the possibility of kidney toxicity. But when pressed to release the letter for all to see, he declined, according to a report from BioPharmaDive, saying that kind of move “might not look like we’re being as respectful as we’d like to be.”

He went on to assure everyone that he hadn’t misrepresented the CRL.

But Ingram’s public remarks didn’t include everything in the letter, which — following the FDA’s surprise about-face and unexplained approval — has now been posted on the FDA’s website and broadly circulated on Twitter early Wednesday.

The CRL raises plenty of fresh questions about why the FDA abruptly decided to reverse itself and hand out an OK for a drug a senior regulator at the FDA believed — 5 months ago, when he wrote the letter — is dangerous to patients. It also puts the spotlight back on Sarepta $SRPT, which failed to launch a confirmatory study of eteplirsen, which was only approved after a heated internal controversy at the FDA. Ellis Unger, director of CDER’s Office of Drug Evaluation I, notes that study could have clarified quite a lot about the benefit and risks associated with their drugs — which can cost as much as a million dollars per patient per year, depending on weight.

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2019 Trin­i­ty Drug In­dex Eval­u­ates Ac­tu­al Com­mer­cial Per­for­mance of Nov­el Drugs Ap­proved in 2016

Fewer Approvals, but Neurology Rivals Oncology and Sees Major Innovations

This report, the fourth in our Trinity Drug Index series, outlines key themes and emerging trends in the industry as we progress towards a new world of targeted and innovative products. It provides a comprehensive evaluation of the performance of novel drugs approved by the FDA in 2016, scoring each on its commercial performance, therapeutic value, and R&D investment (Table 1: Drug ranking – Ratings on a 1-5 scale).

How to cap­i­talise on a lean launch

For start-up biotechnology companies and resource stretched pharmaceutical organisations, launching a novel product can be challenging. Lean teams can make setting a launch strategy and achieving your commercial goals seem like a colossal undertaking, but can these barriers be transformed into opportunities that work to your brand’s advantage?
We spoke to Managing Consultant Frances Hendry to find out how Blue Latitude Health partnered with a fledgling subsidiary of a pharmaceutical organisation to launch an innovative product in a
complex market.
What does the launch environment look like for this product?
FH: We started working on the product at Phase II and now we’re going into Phase III trials. There is a significant unmet need in this disease area, and everyone is excited about the launch. However, the organisation is still evolving and the team is quite small – naturally this causes a little turbulence.

Stephen Hahn, AP

The FDA has de­val­ued the gold stan­dard on R&D. And that threat­ens every­one in drug de­vel­op­ment

Bioregnum Opinion Column by John Carroll

A few weeks ago, when Stephen Hahn was being lightly queried by Senators in his confirmation hearing as the new commissioner of the FDA, he made the usual vow to maintain the gold standard in drug development.

Neatly summarized, that standard requires the agency to sign off on clinical data — usually from two, well-controlled human studies — that prove a drug’s benefit outweighs any risks.

Over the last few years, biopharma has enjoyed an unprecedented loosening over just what it takes to clear that bar. Regulators are more willing to drop the second trial requirement ahead of an accelerated approval — particularly if they have an unmet medical need where patients are clamoring for a therapy.

That confirmatory trial the FDA demands can wait a few years. And most everyone in biopharma would tell you that’s the right thing for patients. They know its a tonic for everyone in the industry faced with pushing a drug through clinical development. And it’s helped inspire a global biotech boom.

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UP­DAT­ED: New play­ers are jump­ing in­to the scram­ble to de­vel­op a vac­cine as pan­dem­ic pan­ic spreads fast

When the CNN news crew in Wuhan caught wind of the Chinese government’s plan to quarantine the city of 11 million people, they made a run for one of the last trains out — their Atlanta colleagues urging them on. On the way to the train station, they were forced to skirt the local seafood market, where the coronavirus at the heart of a brewing outbreak may have taken root.

And they breathlessly reported every moment of the early morning dash.

In shuttering the city, triggering an exodus of masked residents who caught wind of the quarantine ahead of time, China signaled that they were prepared to take extreme actions to stop the spread of a virus that has claimed 17 lives, sickened many more and panicked people around the globe.

CNN helped illustrate how hard all that can be.

The early reaction in the biotech industry has been classic, with small-cap companies scrambling to headline efforts to step in fast. But there are also new players in the field with new tech that has been introduced since the last of a series of pandemic panics that could change the usual storylines. And they’re volunteering for a crash course in speeding up vaccine development — a field where overnight solutions have been impossible to prove.

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Mer­ck KGaA spin­out gets first fund­ing to bring dual-act­ing can­cer mol­e­cules in­to the clin­ic

Two and a half years after launch, Merck KGaA spinout iOnctura is getting its first major round of funding.

The oncology startup raised €15 million ($16.6 million) to put its lead drug into the clinic and get its second drug past IND-enabling tests. INKEF Capital and VI Partners co-led the round and were joined by the biotech’s longtime backer M Ventures, an arm of Merck KGaA, and Schroder Adveq.

UP­DAT­ED: Eli Lil­ly’s $1.6B can­cer drug failed to spark even the slight­est pos­i­tive gain for pa­tients in its 1st PhI­II

Eli Lilly had high hopes for its pegylated IL-10 drug pegilodecakin when it bought Armo last year for $1.6 billion in cash. But after reporting a few months ago that it had failed a Phase III in pancreatic cancer, without the data, its likely value has plunged. And now we’re getting some exact data that underscore just how little positive effect it had.

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Am­gen aug­ments Asia foothold by tak­ing over Astel­las joint ven­ture in Japan

California-based Amgen, which does the bulk of its business in the United States, made its ambition to reinvigorate its growth prospects by expanding its presence in Asia clear at the sidelines of the JP Morgan healthcare conference in San Francisco earlier this month.

The Thousand Oaks-based company on Thursday executed its plan to dissolve the joint venture with Astellas — created in 2013 — to operate the unit independently in Japan. With its rapidly aging population, the region represents an appealing market for Amgen’s osteoporosis treatments Prolia and Evenity as well as a cholesterol-lowering injection Repatha.

Daphne Zohar (PureTech)

PureTech bags $200M from sale of Karuna shares — still siz­zling from promis­ing schiz­o­phre­nia da­ta

Cashing in on the exuberance around Karuna Therapeutics and its potential blockbuster CNS drug, PureTech has sold a chunk of the biotech’s shares to Goldman Sachs for $200 million.

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