Am­gen’s star PhI­II os­teo­poro­sis drug ro­mo slammed by sur­pris­ing car­dio risk, a big plus for ri­val Ra­dius drug

Am­gen’s ro­mosozum­ab, one of its top late-stage drug prospects aimed at os­teo­poro­sis, is in some se­ri­ous trou­ble.

Late Sun­day the big biotech $AMGN and its part­ner UCB an­nounced what at first glance would ap­pear to be hap­py news: the late-stage tri­al com­par­ing ro­mosozum­ab to Fos­amax hit its pri­ma­ry and key sec­ondary end­points. But as you wind through the re­lease, some big is­sues start to rise up that raise se­ri­ous ques­tions about its fu­ture — if it has one. And that could make a big dif­fer­ence for its new­ly ap­proved ri­val at Ra­dius Health $RDUS.

Big event one: There was a no­table car­dio risk im­bal­ance be­tween ro­mo and Fos­amax; 2.5% for ro­mo and 1.9% for Fos­amax.

Big event two: The FDA wants to eval­u­ate the new set of head-to-head da­ta in siz­ing up an ap­proval. And that means no de­ci­sion is ex­pect­ed this sum­mer, as had been as­sumed ear­li­er.

Am­gen shares dropped 2.3% in pre-mar­ket trad­ing, while UCB plunged 14.5%. Ra­dius shares jumped about 15% on the news.

Umer Raf­fat at Ever­core ISI spot­ted the sig­nif­i­cance quick­ly. He not­ed:

Am­gen’s Ph 3 up­date on bone drug just now is clear­ly neg­a­tive, and very sur­pris­ing.  At this point, we are tak­ing out all ro­mo sales from the mod­el.  Con­sen­sus has ~$800M peak for this drug – if you take it out (and bake in the part­ner­ship split with UCB), EPS re­vi­sion of ~$0.32/share.  We sus­pect stock like­ly down ~3-4% on this.

That all sound­ed sus­pi­cious­ly like odanacat­ib, Mer­ck’s os­teo­poro­sis drug which the phar­ma gi­ant de­cid­ed to shelve last fall af­ter wit­ness­ing an in­crease risk of stroke for the drug. And Ge­of­frey Porges at Leerink cal­cu­lat­ed the odds of Am­gen scrap­ping the drug.

We be­lieve that the prod­uct now has on­ly a 50/50 prob­a­bil­i­ty of com­ing to mar­ket at all, and these odds are sub­ject to the re­sults of dis­cus­sions with spe­cial­ists and in­ves­ti­ga­tors, as well as full dis­clo­sure of the na­ture and sever­i­ty of the car­dio­vas­cu­lar events ob­served in both stud­ies.

Just a few weeks ago Ra­dius won their first ever drug ap­proval for abaloparatide, now be­ing lined up for the os­teo­poro­sis mar­ket as Tym­los. An­a­lysts like Ge­of­frey Porges had thought Ra­dius may try to go af­ter a unique mar­ket with a com­mer­cial strat­e­gy tak­ing in­to ac­count Eli Lil­ly’s ag­ing For­teo with the ri­val ro­mosozum­ab from Am­gen and UCB be­ing steered in­to a Ju­ly 19 PDU­FA date.

But that’s at the very least sig­nif­i­cant­ly de­layed — Ra­dius CEO Bob Ward said it nev­er was a fac­tor — as far as ro­mo is con­cerned.

Last fall an­a­lysts were talk­ing more about a straight shot at a quick ap­proval for ro­mo this sum­mer — with some sig­nif­i­cant caveats. 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, which re­cruit­ed 7,180 high-prism post­menopausal women.

But the drug missed a key sec­ondary end­point. The drug did not sig­nif­i­cant­ly im­prove pa­tients’ risk of non-ver­te­bral frac­tures, leav­ing Ra­dius Health — which has post­ed an 86% risk re­duc­tion in ver­te­bral frac­tures — with a pos­si­ble dis­tinct ad­van­tage on that score.

Am­gen and its part­ners at UCB didn’t ig­nore the sit­u­a­tion to­day, af­ter high­light­ing the pos­i­tive.

Iris Loew-Friedrich

“We are im­pressed with the sta­tis­ti­cal­ly sig­nif­i­cant su­pe­ri­or frac­ture risk re­duc­tion of EVENI­TY over al­en­dronate, a cur­rent stan­dard of care in os­teo­poro­sis. When we think that pa­tients who have had a frac­ture are high­ly like­ly to suf­fer an­oth­er one, the im­por­tance of post-frac­ture care can­not be em­pha­sized enough,” said Iris Loew-Friedrich, UCB’s chief med­ical of­fi­cer. “We are work­ing on un­der­stand­ing the ob­served car­dio­vas­cu­lar safe­ty sig­nal and will con­tin­ue to dis­cuss these re­sults with glob­al reg­u­la­tors and ex­perts in the field.”

This is a bad twist for Am­gen. The bio­phar­ma play­er has had a se­ries of is­sues, in­clud­ing a big back­lash by pay­ers tar­get­ing its PC­SK9 drug. Watch­ing an­oth­er late-stage drug go un­der a cloud like this won’t help Am­gen’s rep with an­a­lysts.

At the In­flec­tion Point for the Next Gen­er­a­tion of Can­cer Im­munother­a­py

While oncology researchers have long pursued the potential of cellular immunotherapies for the treatment of cancer, it was unclear whether these therapies would ever reach patients due to the complexity of manufacturing and costs of development. Fortunately, the recent successful development and regulatory approval of chimeric antigen receptor-engineered T (CAR-T) cells have demonstrated the significant benefit of these therapies to patients.

Stéphane Bancel, Moderna CEO

'This is not go­ing to be good': Mod­er­na CEO Ban­cel warns of a 'ma­te­r­i­al drop' in vac­cine ef­fi­ca­cy as Omi­cron spreads

Even as public health officials remain guarded about their comments on the likelihood Omicron will escape the reach of the currently approved Covid-19 vaccines, there’s growing scientific consensus that we’re facing a variant that threatens to overwhelm the vaccine barricades that have been erected.

Stéphane Bancel, the CEO of Moderna, one of the leading mRNA players whose quick vault into the markets with a highly effective vaccine created an instant multibillion-dollar market, added his voice to the rising chorus early Tuesday. According to Bancel, there will be a significant drop in efficacy when the average immune system is confronted by Omicron. The only question now is: How much?

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Philip Dormitzer, new GSK global head of vaccines R&D

Glax­o­SmithK­line poach­es Pfiz­er's vi­ral vac­cines lead in rush to cap­i­tal­ize on fu­ture of mR­NA

GlaxoSmithKline has appointed Philip Dormitzer, formerly chief scientific officer of Pfizer’s viral vaccines unit, as its newest global head of vaccines R&D, looking to leverage one of the leading minds behind Pfizer and BioNTech’s RNA collaboration that led to Covid-19 jab Comirnaty, the British drug giant said Tuesday.

Dormitzer had been with Pfizer for a little more than six years, joining up after a seven-year stint with Novartis, where he reached the role of US head of research and head of global virology for the company’s vaccines and diagnostics unit.

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In­tro­duc­ing End­points Stu­dio, a new way to ad­ver­tise with End­points-craft­ed brand­ing cam­paigns

Since our start in 2016, Endpoints has grown fast while executing our mission to cover biopharma’s most critical developments for industry pros worldwide. As readership has grown, our advertising business has too. Endpoints advertising partners support the mission and engage their desired audiences through announcements on our email and web platforms, brand recognition in our event coverage and sponsorships of Endpoints daily and weekly reports.

As lead drug runs in­to a wall, De­ci­phera slims down its pipeline, puts 140 jobs on the chop­ping block

Barely a month after disappointing data shattered hopes for a major label expansion for the GI tumor drug Qinlock, Deciphera is making a major pivot — scrapping development plans for that drug and discarding another while it hunkers down and focuses on two remaining drugs in the pipeline.

As a result, 140 of its staffers will be laid off.

The restructuring, which claims the equivalent of 35% of its total workforce, will take place across all departments including commercial, R&D as well as general and administrative support functions, Deciphera said, as it looks to streamline Qinlock-related commercial operations in the US while concentrating only on a “select number of key European markets.”

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How to use reg­istry da­ta to sup­port FDA de­ci­sion mak­ing: Agency ex­plains in new guid­ance

Drugmakers looking to design a new registry or use an existing one to support a regulatory decision on a drug’s effectiveness or safety will need to consult with a new draft guidance released Monday by the FDA.

The agency’s reliance on registry data for regulatory decisions dates back more than two decades, at least, as in 1998 Bayer won approval for its anticoagulant Refludan (withdrawn from the market in 2013 for commercial reasons) based in part on a historical control group pulled from a registry.

Tillman Gerngross (Adagio)

Till­man Gern­gross on Omi­cron: 'It is a grim sit­u­a­tion...we’re go­ing to see a sig­nif­i­cant drop in vac­cine ef­fi­ca­cy'

Tillman Gerngross, the rarely shy Dartmouth professor, biotech entrepreneur and antibody expert, has been warning for over a year that the virus behind Covid-19 would likely continue to mutate, potentially in ways that avoid immunity from infection and the best defenses scientists developed. He spun out a company, Adagio, to build a universal antibody, one that could snuff out any potential mutation.

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In­cor­po­rat­ing Ex­ter­nal Da­ta in­to Clin­i­cal Tri­als: Com­par­ing Dig­i­tal Twins to Ex­ter­nal Con­trol Arms

Most drug development professionals are familiar with the nerve-racking wait for the read-out of a large trial. If it’s negative, is the investigational therapy ineffective? Or could the failure result from an unforeseen flaw in the design or execution of the protocol, rather than a lack of efficacy? The team could spend weeks analyzing data, but a definitive answer may be elusive due to insufficient power for such analyses in the already completed trial. These problems are only made worse if the trial had lower enrollment, or higher dropout than expected due to an unanticipated event like COVID-19. And if a trial is negative, the next one is likely to be larger and more costly — if it happens at all.

Mar­ket­ingRx roundup: Ab­b­Vie’s Hu­mi­ra TV turns fo­cus to HS skin con­di­tion; Sanofi amps par­ent­ing pol­i­cy

After years as the top spending pharma TV advertiser, AbbVie’s Humira brand finally downshifted earlier this year, ceding much of its marketing budget to up-and-coming sibling meds Skyrizi and Rinvoq. However, now Humira is back on TV with ads for another condition — Hidradenitis suppurativa (HS).

The chronic and painful skin condition results in lumps and abscesses caused by inflammation or infection of sweat glands, most often in the armpits or groin. Humira was first approved to treat HS in 2015 and remains the only FDA-approved drug for the condition. Two TV ads both note more than 30,000 people with HS have been prescribed Humira.