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.

Secretary of health and human services Alex Azar speaking in the Rose Garden at the White House (Photo: AFP)

Trump’s HHS claims ab­solute au­thor­i­ty over the FDA, clear­ing path to a vac­cine EUA

The top career staff at the FDA has vowed not to let politics overrule science when looking at vaccine data this fall. But Alex Azar, who happens to be their boss’s boss, apparently won’t even give them a chance to stand in the way.

In a new memorandum issued Tuesday last week, the HHS chief stripped the FDA and other health agencies under his purview of their rule making ability, asserting all such power “is reserved to the Secretary.” Sheila Kaplan of the New York Times first obtained and reported the details of the September 15 bulletin.

#ES­MO20: Push­ing in­to front­line, Mer­ck and Bris­tol My­ers duke it out with new slate of GI can­cer da­ta

Having worked in parallel for years to move their respective PD-1 inhibitors up to the first-line treatment of gastrointestinal cancers, Merck and Bristol Myers Squibb finally have the data at ESMO for a showdown.

Comparing KEYNOTE-590 and CheckMate-649, of course, comes with the usual caveats. But a side-by-side look at the overall survival numbers also offer some perspective on a new frontier for the reigning checkpoint rivals, both of whom are claiming to have achieved a first.

President Donald Trump (via AP Images)

Signs of an 'Oc­to­ber Vac­cine Sur­prise' alarm ca­reer sci­en­tists

President Donald Trump, who seems intent on announcing a COVID-19 vaccine before Election Day, could legally authorize a vaccine over the objections of experts, officials at the FDA and even vaccine manufacturers, who have pledged not to release any vaccine unless it’s proved safe and effective.

In podcasts, public forums, social media and medical journals, a growing number of prominent health leaders say they fear that Trump — who has repeatedly signaled his desire for the swift approval of a vaccine and his displeasure with perceived delays at the FDA — will take matters into his own hands, running roughshod over the usual regulatory process.

#ES­MO20: Bris­tol My­ers marks Op­di­vo's sec­ond ad­ju­vant win — eye­ing a stan­dard of care gap

Moving into earlier and earlier treatment lines, Bristol Myers Squibb is reporting that adjuvant treatment with Opdivo has doubled the time that esophageal or gastroesophageal junction cancer patients stay free of disease.

With the CheckMate-577 data at ESMO, CMO Samit Hirawat said, the company believes it can change the treatment paradigm.

While a quarter to 30% of patients typically achieve a complete response following chemoradiation therapy and surgery, the rest do not, said Ronan Kelly of Baylor University Medical Center. The recurrence rate is also high within the first year, Hirawat added.

Clay Siegall (Life Science Washington via YouTube)

#ES­MO20: Seat­tle Ge­net­ics eyes 4th ap­proval with new da­ta in a crowd­ed field

Does Seattle Genetics have another approval on its hands?

The last 12 months, not so great for the world, has been great for Seattle Genetics. The company landed two separate FDA approvals, signed a $4.5 billion deal with Merck and watched antibody-drug conjugates — the technology they spent years developing to broad industry skepticism — emerge suddenly as one of the most popular approaches in oncology. And on Monday at ESMO, the company and their partners at Genmab unveiled the data behind the ADC it hopes will provide its next major FDA approval.

Jonathan Rigby, Immune Regulation group CEO

Im­mune Reg­u­la­tion, tak­ing two clin­i­cal pro­grams to 're­set' the im­mune sys­tem, nets $53M+ Se­ries B

A little under two years after a company rebranding, Immune Regulation is taking an even bigger step toward advancing its goals.

Formerly known as Peptinnovate, the British biotech announced a $53.4 million Series B early Monday morning, helping to further advance two clinical programs in rheumatoid arthritis and asthma. Though those are the two initial indications the company is focusing on, CEO Jonathan Rigby told Endpoints News he hopes the candidates can be applied to a broad swath of autoimmune disorders.

Eli Lilly CSO Dan Skovronsky (file photo)

UP­DAT­ED: #ES­MO20: Eli Lil­ly shows off the da­ta for its Verzenio suc­cess. Was it worth $18 bil­lion?

The press release alone, devoid of any number except for the size of the trial, added nearly $20 billion to Eli Lilly’s market cap back in June. Now investors and oncologists will get to see if the data live up to the hype.

On Sunday at ESMO, Eli Lilly announced the full results for its Phase III MonarchE trial of Verzenio, showing that across over 5,000 women who had had HR+, HER2- breast cancer, the drug reduced the odds of recurrence by 25%. That meant 7.8% of the patients on the drug arm saw their cancers return within 2 years, compared with 11.3% on the placebo arm.

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Greg Friberg (File photo)

#ES­MO20: Am­gen team nails down sol­id ear­ly ev­i­dence of AMG 510’s po­ten­tial for NSCLC, un­lock­ing the door to a wave of KRAS pro­grams

The first time I sat down with Amgen’s Greg Friberg to talk about the pharma giant’s KRAS G12C program for sotorasib (AMG 510) at ASCO a little more than a year ago, there was high excitement about the first glimpse of efficacy from their Phase I study, with 5 of 10 evaluable non-small cell lung cancer patients demonstrating a response to the drug.

After decades of failure targeting KRAS, sotorasib offered the first positive look at a new approach that promised to open a door to a whole new approach by targeting a particular mutation to a big target that had remained “undruggable” for decades.

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#ES­MO20: Out to beat Tagris­so, J&J touts 100% ORR for EGFR bis­pe­cif­ic/TKI com­bo — fu­el­ing a quick leap to PhI­II

J&J’s one-two punch on EGFR-mutant non-small cell lung cancer has turned up some promising — although decidedly early — results, fueling the idea that there’s yet room to one up on third-generation tyrosine kinase inhibitors.

Twenty out of 20 advanced NSCLC patients had a response after taking a combination of an in-house TKI dubbed lazertinib and amivantamab, a bispecific antibody targeting both EGFR and cMET engineered on partner Genmab’s platform, J&J reported at ESMO. All were treatment-naïve, and none has seen their cancer progress at a median follow-up of seven months.