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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.

Health­care Dis­par­i­ties and Sick­le Cell Dis­ease

In the complicated U.S. healthcare system, navigating a serious illness such as cancer or heart disease can be remarkably challenging for patients and caregivers. When that illness is classified as a rare disease, those challenges can become even more acute. And when that rare disease occurs in a population that experiences health disparities, such as people with sickle cell disease (SCD) who are primarily Black and Latino, challenges can become almost insurmountable.

The End­points 11: They've got mad mon­ey and huge am­bi­tions. It's time to go big or go home

These days, selecting a group of private biotechs for the Endpoints 11 spotlight begins with a sprint to get ahead of IPOs and the M&A teams at Big Pharma. I’ve had a couple of faceplants earlier this year, watching some of the biotechs on my short list choose a quick leap onto Nasdaq or into the arms of a buyer.

Vividion, you would have been a great pick for the Endpoints 11. I’m sorry I missed you.

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Dave Lennon, former president of Novartis Gene Therapies

So what hap­pened with No­var­tis Gene Ther­a­pies? Here's your an­swer

Over the last couple of days it’s become clear that the gene therapy division at Novartis has quietly undergone a major reorganization. We learned on Monday that Dave Lennon, who had pursued a high-profile role as president of the unit with 1,500 people, had left the pharma giant to take over as CEO of a startup.

Like a lot of the majors, Novartis is an open highway for head hunters, or anyone looking to staff a startup. So that was news but not completely unexpected.

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Who are the women su­per­charg­ing bio­phar­ma R&D? Nom­i­nate them for this year's spe­cial re­port

The biotech industry has faced repeated calls to diversify its workforce — and in the last year, those calls got a lot louder. Though women account for just under half of all biotech employees around the world, they occupy very few places in C-suites, and even fewer make it to the helm.

Some companies are listening, according to a recent BIO survey which showed that this year’s companies were 2.5 times more likely to have a diversity and inclusion program compared to last year’s sample. But we still have a long way to go. Women represent just 31% of biotech executives, BIO reported. And those numbers are even more stark for women of color.

Emma Walmsley, GlaxoSmithKline CEO (Credit: Fang Zhe/Xinhua/Alamy Live News)

The fire un­der Glax­o­SmithK­line's Em­ma Walm­s­ley grows as an­oth­er well-known ac­tivist in­vestor grabs its pitch­fork — re­port

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The London-based hedge fund joins another notorious activist firm in Paul Singer’s Elliott Management, which earlier this year called for a shakeup in leadership at GSK to handle what the company described as a wealth of riches across the drug giant’s portfolio hindered by limited vision from top staff.

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The Biden administration’s goal of kicking off its booster shot drive for the entire US population this week is not quite going as planned.

First, Pfizer applied for approval of a supplemental application for the booster shots, but since last Friday’s adcomm reviewing them, the plan has devolved into an EUA, which the FDA issued late Thursday evening.

The population that is now eligible for the booster, six months after receiving the first pair of Pfizer-BioNTech vaccines, also narrowed from what Pfizer applied for (everyone who’s eligible for the initial Pfizer shots) to just those who are 65 or older, or at high-risk of a Covid infection, including health care workers and others with occupational hazards.

Stéphane Bancel, AP Images

Fi­nal analy­sis of US-fund­ed Mod­er­na Covid vac­cine tri­al shows 98% ef­fi­ca­cy against se­vere dis­ease

A final look at the results of the placebo-controlled Moderna trial in the New England Journal of Medicine, published Thursday afternoon, shows how the vaccine continues to prevent Covid-19 and severe cases after more than five months following the second shot.

Of the more than 30,000 enrolled in the trial that ultimately led to the vaccine’s EUA, only two people in the vaccine group got a severe form of the disease, compared to 106 in the placebo group — leading to an efficacy of 98%.

FDA+ roundup: Bs­U­FA III ready for show­time, court tells FDA to re-work com­pound­ing plan, new guid­ance up­dates and more

The FDA has now spelled out what exactly will be included in the third iteration of Biosimilar User Fee Act (BsUFA) from 2023 through 2027, which similarly to the prescription drug deal, sets fees that industry has to pay for submitting applications, in exchange for firm timelines that the agency must meet.

This latest deal includes several sweeteners for the biosimilar industry, which has yet to make great strides in the US market, with shorter review timelines for safety labeling updates and updates to add or remove an indication that does not contain efficacy data.

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Jean Bennett (Brent N. Clarke/Invision/AP Images)

Lux­tur­na in­ven­tor Jean Ben­nett starts a new gene ther­a­py com­pa­ny to tack­le rare dis­eases left be­hind by phar­ma, VCs

A few years ago Jean Bennett found herself in a surprising place for a woman who invented the first gene therapy ever approved in the United States: No one, it seemed, wanted her work.

Bennett, who designed and co-developed Luxturna, approved in 2018 for a rare form of blindness, had kept building new gene therapies for eye diseases at her University of Pennsylvania lab. But although the results in animals looked promising, pharma companies and investors kept turning down the pedigreed ophthalmology professor.

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