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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.

Mov­ing Out of the Clin­ic with Dig­i­tal Tools: Mo­bile Spirom­e­try Dur­ing COVID-19 & Be­yond

An important technology in assessing lung function, spirometry offers crucial data for the diagnosis and monitoring of pulmonary system diseases, as well as the ongoing measurement of treatment efficacy. But trends in the healthcare industry and new challenges introduced by the COVID-19 pandemic are causing professionals in clinical practice and research to reevaluate spirometry’s deployment methods and best practices.

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Sanofi, Glax­o­SmithK­line jump back in­to the PhI­II race for a Covid vac­cine — as the win­ners con­gre­gate be­hind the fin­ish line

Sanofi got out early in the race to develop a vaccine using more of a traditional approach, then derailed late last year as their candidate failed to work in older people. Now, after likely missing the bus for the bulk of the world’s affluent nations, they’re back from that embarrassing collapse with a second attempt using GSK’s adjuvant that may get them back on track — with a potential Q4 launch that the rest of the world will be paying close attention to.

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SCO­TUS de­clines to re­view En­brel biosim­i­lar case, tee­ing up 30+ years of ex­clu­siv­i­ty and $20B more for Am­gen’s block­buster

As the House Oversight Committee is set to grill AbbVie CEO Richard Gonzalez on Tuesday over tactics to block competition for its best-selling drug of all time, another decision on Capitol Hill on Monday opened the door for billions more in Amgen profits over the next eight years.

The Supreme Court on Monday denied Novartis subsidiary Sandoz’s petition to review a Federal Circuit’s July 2020 decision concerning its biosimilar Erelzi (etanercept-szzs), which FDA approved in 2016 as a biosimilar to Amgen’s Enbrel (etanercept). Samsung’s Enbrel biosimilar Eticovo also won approval in 2019 and remains sidelined.

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No­var­tis' En­tresto takes its 2nd fail­ure of the week­end at ACC, show­ing no ben­e­fit in most dire heart fail­ure pa­tients

Novartis’ Entresto started the ACC weekend off rough with a trial flop in heart attack patients, slowing the drug’s push into earlier patients. Now, an NIH-sponsored study is casting doubt on Entresto’s use in the most severe heart failure patients, another black mark on the increasingly controversial drug’s record.

Entresto, a combination of sacubitril and valsartan, could not beat out valsartan alone in an outcomes head-to-head for severe heart failure patients with a reduced ejection fraction (HFrEF), according to data presented Monday at the virtual American College of Cardiology meeting.

How to man­u­fac­ture Covid-19 vac­cines with­out the help of J&J, Pfiz­er or Mod­er­na? Bi­ol­yse sees the dif­fi­cul­ties up close

When Biolyse, an Ontario-based manufacturer of sterile injectables, forged a deal with Bolivia last week to manufacture up to 50 million J&J Covid-19 vaccine doses, the agreement kicked off what will prove to be a test case for how difficult the system of compulsory licenses is to navigate.

The first problem: When Biolyse asked J&J, via a March letter, to license its Covid-19 vaccine, manufacture it in Canada and pay 5% royalties on shipments to needy, low-income countries, J&J rejected the offer, refusing to negotiate. J&J also did not respond to a request for comment.

Tim Mayleben (L) and Sheldon Koenig (Esperion)

On the heels of a sting­ing Q1 set­back, Es­pe­ri­on's long­time cham­pi­on is ex­it­ing the helm and turn­ing the wheel over to a mar­ket­ing pro

Just days after getting stung by criticism from a badly disappointed group of analysts, there’s a big change happening today at the helm of Esperion $ESPR.

Longtime CEO Tim Mayleben, who championed the company for 9 years from early clinical through a lengthy late-stage drive to successfully get their cholesterol drug approved for a significant niche of patients in the US, is out of the C suite, effective immediately. Sheldon Koenig — hired at the end of 2020 with a resume replete with Big Pharma CV sales experience —  is stepping into his place, promising to right a badly listing commercial ship that’s been battered by market forces.

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Matt Gline (L) and Vivek Ramaswamy

In­sid­er ac­count of Roivan­t's SPAC deal — and that $7.3B val­u­a­tion — re­veals a few se­crets as Matt Gline po­si­tions the com­pa­ny as the new ‘Big Phar­ma’

It was Oct. 7, 2020, and Matt Gline wasn’t wasting any time.

The CEO of Roivant had word that KKR vet Jim Momtazee’s SPAC had priced late the night before, triggering a green light for anyone interested in pursuing a big check for future operations and riding the financial instrument to Nasdaq. So he wrote a quick email congratulating Momtazee, whom he knew, for the launch.

Oh, and maybe Momtazee would like to schedule something with Gline and his executive chairman, Roivant founder Vivek Ramaswamy, to chat about Roivant and its business?

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Re­gen­eron's Evkeeza shows promise in curb­ing high triglyc­erides, but will ge­net­ic dis­par­i­ties lim­it use?

When Regeneron scored an early approval for lipid lowering antibody Evkeeza back in February, the drugmaker cracked open a new pathway to lower abnormally high cholesterol levels. Now, Regeneron is chasing high triglycerides as well with some promising mid-stage data — but will genetic restrictions limit the drug’s use?

Regeneron’s Evkeeza (evinacumab) cut median triglyceride levels by more than 800 mg/dL (57%) in patients with a rare disorder causing abnormally high triglyceride levels compared with an overall increase of 50 mg/dL (1.8%) in participants on placebo, according to Phase II data presented Sunday at the virtual American College of Cardiology meeting.

Pascal Soriot, AstraZeneca CEO (AP Images)

As­traZeneca's Farx­i­ga missed big on Covid-19 study, but it's tak­ing SGLT2 safe­ty da­ta as a sil­ver lin­ing

AstraZeneca hasn’t seen many setbacks in recent months for SGLT2 inhibitor Farxiga, which broke ground in heart failure and kidney disease regardless of diabetes diagnosis. But the British drugmaker had to admit defeat in taking Farxiga into Covid-19. However, follow-up results add a bit of a silver lining to that trial’s safety data.

Of hospitalized Covid-19 patients dosed with AstraZeneca’s Farxiga, 11.2% experienced an organ failure or died after 30 days of therapy compared with 13.8% of those given placebo, according to follow-up data from the DARE-19 study revealed Sunday at the virtual American College of Cardiology meeting.