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Bay­er, Ori­on win speedy ap­proval for prostate can­cer drug daro­lu­tamide

Three months ahead of sched­ule, Bay­er and Finnish part­ner Ori­on’s prostate can­cer drug daro­lu­tamide has been cleared for use by the US reg­u­la­tor un­der pri­or­i­ty re­view. The an­dro­gen re­cep­tor (AR) in­hibitor will be mar­ket­ed as Nube­qa, and it was ap­proved for pa­tients with cas­tra­tion-re­sis­tant prostate can­cer that has not spread to oth­er parts of the body (nm­CR­PC).

Prostate can­cer is the sec­ond most com­mon­ly di­ag­nosed ma­lig­nan­cy in men glob­al­ly, and treat­ment op­tions in­clude surgery, ra­di­a­tion treat­ment and ther­a­py us­ing hor­mone-re­cep­tor an­tag­o­nists. How­ev­er, in near­ly every case, the can­cer grows re­sis­tant to con­ven­tion­al hor­mone ther­a­py and can spread to oth­er parts of the body. Cas­tra­tion-re­sis­tant prostate can­cer (CR­PC) is an ad­vanced form of the dis­ease and is char­ac­ter­ized by per­sis­tent, high lev­el AR func­tion and re­sis­tance to con­ven­tion­al an­ti-an­dro­gens.

The Ger­man drug­mak­er agreed to de­vel­op the drug with Fin­land’s Ori­on {ORN­BV: $FH} in 2014, the same year the Phase III ARAMIS tri­al com­menced. The class of drugs is de­signed to block the growth of can­cer cells by bind­ing to the an­dro­gen re­cep­tor and in­hibit­ing its func­tion.

The com­pa­nies first re­port­ed the drug had met the main goal in the ARAMIS tri­al last Oc­to­ber. The tri­al test­ed daro­lu­tamide against a place­bo in more than 1,500 pa­tients with nm­CR­PC that were al­ready on stan­dard-of-care an­dro­gen de­pri­va­tion ther­a­py, and were at high risk of the dis­ease spread­ing. Da­ta showed the drug met the pri­ma­ry end­point of in­duc­ing a sta­tis­ti­cal­ly sig­nif­i­cant im­prove­ment in metas­ta­sis-free sur­vival (MFS) (HR=0.41 and p val­ue<0.001) com­pared to place­bo, which trans­lates to a 59% re­duc­tion in the risk of metas­ta­sis or death in nm­CR­PC pa­tients, Bay­er said, adding that me­di­an MFS was 40.4 months in the daro­lu­tamide arm ver­sus 18.4 months for the place­bo co­hort.

The sec­ondary end­points in the tri­al in­clud­ed over­all sur­vival (OS), time to pain pro­gres­sion and time to ini­ti­a­tion of first cy­to­tox­ic chemother­a­py, and each met­ric sug­gest­ed a trend fa­vor­able to daro­lu­tamide, the com­pa­nies sug­gest­ed.

Bay­er, which al­ready sells Xofi­go for metasta­t­ic prostate can­cer, will take Nube­qa to mar­ket with ex­ist­ing com­peti­tors. Al­though Pfiz­er’s $PFE Xtan­di (en­za­lu­tamide), as well as J&J’s $JNJ new­er Er­lea­da (apa­lu­tamide), are non-steroidal an­dro­gen re­cep­tor in­hibitors ap­proved to treat nm­CR­PC pa­tients like Nube­qa, the lat­ter is poised to take a bite of sales due to its more-be­nign safe­ty pro­file, HC Wain­wright an­a­lyst Raghu­ram Sel­vara­ju wrote in a March note, cit­ing a prostate can­cer ex­pert.

“(W)hile en­za­lu­tamide and apa­lu­tamide are vir­tu­al­ly in­ter­change­able—and, in­deed, dif­fer by on­ly a sin­gle sub­stituent from a chem­i­cal struc­ture stand­point—daro­lu­tamide is dif­fer­ent and may in­deed be deemed su­pe­ri­or, par­tic­u­lar­ly from a safe­ty per­spec­tive,” he wrote, cit­ing Em­manuel An­tonarakis, who serves as as­so­ciate pro­fes­sor at Johns Hop­kins School of Med­i­cine and as a med­ical on­col­o­gist at the Sid­ney Kim­mel Com­pre­hen­sive Can­cer Cen­ter in Bal­ti­more.

“Both en­za­lu­tamide and apa­lu­tamide have been linked to var­i­ous cen­tral side ef­fects, par­tic­u­lar­ly fa­tigue and loss of bal­ance, while daro­lu­tamide does not ap­pear to ex­hib­it brain or CNS tis­sue pen­e­trance and thus lacks these draw­backs. Ac­cord­ing­ly…daro­lu­tamide could…even­tu­al­ly as­cend to the lead­er­ship po­si­tion among sec­ond-gen­er­a­tion AR an­tag­o­nists.”

Bay­er and Ori­on have filed for the drug’s ap­proval in the Eu­ro­pean Union, Japan and with oth­er health au­thor­i­ties. An­oth­er tri­al eval­u­at­ing daro­lu­tamide in pa­tients with metasta­t­ic hor­mone-sen­si­tive prostate can­cer (mH­SPC) is on­go­ing, and is ex­pect­ed to be com­plet­ed in 2022.

It’s fi­nal­ly over: Bio­gen, Ei­sai scrap big Alzheimer’s PhI­I­Is af­ter a pre­dictable BACE cat­a­stro­phe rais­es safe­ty fears

Months after analysts and investors called on Biogen and Eisai to scrap their BACE drug for Alzheimer’s and move on in the wake of a string of late-stage failures and rising safety fears, the partners have called it quits. And they said they were dropping the drug — elenbecestat — after the independent monitoring board raised concerns about…safety.

We don’t know exactly what researchers found in this latest catastrophe, but the companies noted in their release that investigators had determined that the drug was flunking the risk/benefit analysis.

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Deborah Dunsire. Lundbeck

Deb­o­rah Dun­sire is pay­ing $2B for a chance to leap di­rect­ly in­to a block­buster show­down with a few of the world's biggest phar­ma gi­ants

A year after taking the reins as CEO of Lundbeck, Deborah Dunsire is making a bold bid to beef up the Danish biotech’s portfolio of drugs in what will likely be a direct leap into an intense rivalry with a group of giants now carving up a growing market for new migraine drugs.

Bright and early European time the company announced that it will pay up to about $2 billion to buy Alder, a little biotech that is far along the path in developing a quarterly IV formulation for a CGRP drug aimed at cutting back the number of crippling migraines patients experience each month.

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Lisa M. DeAngelis, MSKCC

MSK picks brain can­cer ex­pert Lisa DeAn­ge­lis as its next CMO — fol­low­ing José Basel­ga’s con­tro­ver­sial ex­it

It’s official. Memorial Sloan Kettering has picked a brain cancer expert as its new physician-in-chief and CMO, replacing José Baselga, who left under a cloud after being singled out by The New York Times and ProPublica for failing to properly air his lucrative industry ties.

His replacement, who now will be in charge of MSK’s cutting-edge research work as well as the cancer care delivered by hundreds of practitioners, is Lisa M. DeAngelis. DeAngelis had been chair of the neurology department and co-founder of MSK’s brain tumor center and was moved in to the acting CMO role in the wake of Baselga’s departure.

Penn team adapts CAR-T tech, reengi­neer­ing mouse cells to treat car­diac fi­bro­sis

After establishing itself as one of the pioneer research centers in the world for CAR-T cancer therapies, creating new attack vehicles to eradicate cancer cells, a team at Penn Medicine has begun the tricky transition of using the basic technology for heart repair work.

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Tal Zaks. Moderna

The mR­NA uni­corn Mod­er­na has more ear­ly-stage hu­man da­ta it wants to show off — reach­ing new peaks in prov­ing the po­ten­tial

The whole messenger RNA field has attracted billions of dollars in public and private investor cash gambled on the prospect of getting in on the ground floor. And this morning Boston-based Moderna, one of the leaders in the field, wants to show off a few more of the cards it has to play to prove to you that they’re really in the game.

The whole hand, of course, has yet to be dealt. And there’s no telling who gets to walk with a share of the pot. But any cards on display at this point — especially after being accused of keeping its deck under lock and key — will attract plenty of attention from some very wary, and wired, observers.

“In terms of the complexity and unmet need,” says Tal Zaks, the chief medical officer, “this is peak for what we’ve accomplished.”

Moderna has two Phase I studies it wants to talk about now.

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It's not per­fect, but it's a good start: FDA pan­elists large­ly en­dorse Aim­mune's peanut al­ler­gy ther­a­py

Two days after a fairly benign review from FDA staff, an independent panel of experts largely endorsed the efficacy and safety of Aimmune’s peanut allergy therapy, laying the groundwork for approval with a risk evaluation and mitigation strategy (REMS).

Traditionally, peanut allergies are managed by avoidance, but the threat of accidental exposure cannot be nullified. Some allergists have devised a way to dose patients off-label with peanut protein derived from supermarket products to wean them off their allergies. But the idea behind Aimmune’s product was to standardize the peanut protein, and track the process of desensitization — so when accidental exposure in the real world invariably occurs, patients are less likely to experience a life-threatening allergic reaction.

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Rit­ter bombs fi­nal PhI­II for sole lac­tose in­tol­er­ance drug — shares plum­met

More than two years ago Ritter Pharmaceuticals managed to find enough silver lining in its Phase IIb/III study — after missing the top-line mark — to propel its lactose intolerance toward a confirmatory trial. But as it turned out, the enthusiasm only set the biotech and its investors up to be sorely disappointed.

This time around there’s little left to salvage. Not only did RP-G28 fail to beat placebo in reducing lactose intolerance symptoms, patients in the treatment group actually averaged a smaller improvement. On a composite score measuring symptoms like abdominal pain, cramping, bloating and gas, patients given the drug had a mean reduction of 3.159 while the placebo cohort saw a 3.420 drop on average (one-sided p-value = 0.0106).

Ear­ly snap­shot of Ad­verum's eye gene ther­a­py sparks con­cern about vi­sion loss

An early-stage update on Adverum Biotechnologies’ intravitreal gene therapy has triggered investor concern, after patients with wet age-related macular degeneration (AMD) saw their vision deteriorate, despite signs that the treatment is improving retinal anatomy.

Adverum, on Wednesday, unveiled 24-week data from the OPTIC trial of its experimental therapy, ADVM-022, in six patients who have been administered with one dose of the therapy. On average, patients in the trial had severe disease with an average of 6.2 anti-VEGF injections in the eight months prior to screening and an average annualized injection frequency of 9.3 injections.

Alex Ar­faei trades his an­a­lyst's post for a new role as biotech VC; Sanofi vet heads to Vi­for

Too often, Alex Arfaei arrived too late. 

An analyst at BMO Capital Markets, he’d meet with biotech or pharmaceutical heads for their IPO or secondary funding and his brain, trained on a biology degree and six years at Merck and Endo, would spring with questions: Why this biomarker? Why this design? Why not this endpoint? Not that he could do anything about it. These execs were coming for clinical money; their decisions had been made and finalized long ago.