Bay­er, Ori­on prostate can­cer drug cuts risk of metas­ta­sis or death by more than 50% in key study

As Mer­ck and Bris­tol-My­ers look to­ward prostate can­cer as the next bat­tle­ground for im­muno-on­col­o­gy dom­i­nance, Bay­er and part­ner Ori­on broke out the num­bers that showed their drug, daro­lu­tamide, cut the risk of metas­ta­sis or death by 59% in a late-stage tri­al in pa­tients with non-metasta­t­ic cas­tra­tion-re­sis­tant prostate can­cer (nm­CR­PC).

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 non-metasta­t­ic cas­tra­tion-re­sis­tant prostate can­cer (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.

Karim Fizazi

“These da­ta are ex­cit­ing for the prostate can­cer com­mu­ni­ty, as they show daro­lu­tamide’s po­ten­tial to treat asymp­to­matic nm­CR­PC pa­tients and de­lay spread of the dis­ease,” said Karim Fizazi, pro­fes­sor of med­i­cine at the In­sti­tut Gus­tave Roussy at the Uni­ver­si­ty of Paris SudFrance in a state­ment

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. 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 AR in­hibitor daro­lu­tamide 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.

Bay­er, which al­ready sells Xofi­go for metasta­t­ic prostate can­cer, said it plans to dis­cuss ARAMIS da­ta with health reg­u­la­tors re­gard­ing mar­ket­ing ap­pli­ca­tions. The drug has al­ready se­cured fast-track sta­tus with the FDA as a treat­ment for nm­CR­PC. But Bay­er may be late to the par­ty, with oth­er such an­dro­gen re­cep­tor in­hibitors such as Pfiz­er’s $PFE Xtan­di as well as J&J’s $JNJ new­er Er­lea­da al­ready on the mar­ket.

An­oth­er tri­al eval­u­at­ing daro­lu­tamide in pa­tients with metasta­t­ic hor­mone-sen­si­tive prostate can­cer (mH­SPC) is on­go­ing, and is ex­pect­ed to be com­plet­ed in 2022.

IM­brave150: Roche’s reg­u­la­to­ry crew plans a glob­al roll­out of Tecen­triq com­bo for liv­er can­cer as PhI­II scores a hit

Just weeks after Bristol-Myers Squibb defended its failed pivotal study pitting Opdivo against Nexavar in liver cancer, Roche says it’s beat the frontline challenge with a combination of their PD-L1 Tecentriq with Avastin. And now they’re rolling their regulatory teams in the US, Europe and China in search of a new approval — badly needed to boost a trailing franchise effort.
Given their breakthrough and Big Pharma status as well as the use of two approved drugs, FDA approval may well prove to be something of a formality. And the Chinese have been clear that they want new drugs for liver cancer, where lethal disease rates are particularly high.
Researchers at their big biotech sub, Genentech, say that the combo beat Bayer’s Nexavar on both progression-free survival as well as overall survival — the first advance in this field in more than a decade. We won’t get the breakdown in months of life gained, but it’s a big win for Roche, which has lagged far, far behind Keytruda and Opdivo, the dominant PD-1s that have captured the bulk of the checkpoint market so far.
Researchers recruited hepatocellular carcinoma — the most common form of liver cancer — patients for the IMbrave150 study who weren’t eligible for surgery ahead of any systemic treatment of the disease.
Roche has a fairly low bar to beat, with modest survival benefit for Nexavar, approved for this indication 12 years ago. But they also plan to offer a combo therapy that could have significantly less toxicity, offering patients a much easier treatment regimen.
Cowen’s Steven Scala recently sized up the importance of IMbrave150, noting:

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 62,500+ biopharma pros reading Endpoints daily — and it's free.

UP­DAT­ED: Clay Sie­gall’s $614M wa­ger on tu­ca­tinib pays off with solid­ly pos­i­tive piv­otal da­ta and a date with the FDA

Back at the beginning of 2018, Clay Siegall snagged a cancer drug called tucatinib with a $614 million cash deal to buy Cascadian. It paid off today with a solid set of mid-stage data for HER2 positive breast cancer that will in turn serve as the pivotal win Siegall needs to seek an accelerated approval in the push for a new triplet therapy.

And if all the cards keep falling in its favor, they’ll move from 1 drug on the market to 3 in 2020, which is shaping up as a landmark year as Seattle Genetics prepares for its 23rd anniversary on July 15.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 62,500+ biopharma pros reading Endpoints daily — and it's free.

Med­ical an­i­ma­tion: Mak­ing it eas­i­er for the site and the pa­tient to un­der­stand

Medical animation has in recent years become an increasingly important tool for conveying niche information to a varied audience, particularly to those audiences without expertise in the specialist area. Science programmes today, for example, have moved from the piece-to-camera of the university professor explaining how a complex disease mechanism works, to actually showing the viewer first-hand what it might look like to shrink ourselves down to the size of an ant’s foot, and travel inside the human body to witness these processes in action. Effectively communicating a complex disease pathophysiology, or the novel mechanism of action of a new drug, can be complex. This is especially difficult when the audience domain knowledge is limited or non-existent. Medical animation can help with this communication challenge in several ways.
Improved accessibility to visualisation
Visualisation is a core component of our ability to understand a concept. Ask 10 people to visualise an apple, and each will come up with a slightly different image, some apples smaller than others, some more round, some with bites taken. Acceptable, you say, we can move on to the next part of the story. Now ask 10 people to visualise how HIV’s capsid protein gets arranged into the hexamers and pentamers that form the viral capsid that holds HIV’s genetic material. This request may pose a challenge even to someone with some virology knowledge, and it is that inability to effectively visualise what is going on that holds us back from fully understanding the rest of the story. So how does medical animation help us to overcome this visualisation challenge?

Alex­ion clinch­es aHUS ap­proval for Ul­tomiris as the clock ticks on Soliris con­ver­sion

Alexion has racked up a second approval for Ultomiris, the successor therapy to Soliris, as its mainstay blockbuster therapy faces a patent review process that could drastically shorten its patent exclusivity.

The FDA OK for atypical hemolytic uremic syndrome (aHUS) on Friday was widely expected after Alexion posted a full slate of positive Phase III data in January. But regulators also flagged concerns about serious meningococcal infections, slapping a black box warning on the label and mandating a REMS.

FDA ap­proval lets Foamix set its maid­en ac­ne ther­a­py on course for US mar­ket launch

Months ago, Foamix leaned on its biggest shareholders — Perceptive Advisors and OrbiMed — to financially grease its wheels, ahead of the FDA decision date for its acne therapy. On Friday, that approval came in — and the topical formulation of the antibiotic minocycline is set for a January launch.

The therapy, Amzeeq (formerly known as FMX101), was approved to treat inflammatory lesions of non-nodular moderate-to-severe acne vulgaris in patients aged 9 and older.

Alice Shaw, Lung Cancer Foundation of America

Top ALK ex­pert and can­cer drug re­searcher Al­ice Shaw bids adieu to acad­e­mia, hel­lo to No­var­tis

Jay Bradner has recruited a marquee oncology drug researcher into the ranks of the Novartis Institutes for BioMedical Research. Alice Shaw is jumping from prestigious posts intertwined through Mass General, Harvard and Dana-Farber to take the lead of NIBR’s translational clinical oncology group.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 62,500+ biopharma pros reading Endpoints daily — and it's free.

Hal Barron, GSK's president of R&D and CSO, speaks to Endpoints News founder and editor John Carroll in London at Endpoints' #UKBIO19 summit on October 8, 2019

[Video] Cel­e­brat­ing tri­al fail­ures, chang­ing the cul­ture and al­ly­ing with Cal­i­for­nia dream­ers: R&D chief Hal Bar­ron talks about a new era at GSK

Last week I had a chance to sit down with Hal Barron at Endpoints’ #UKBIO19 summit to discuss his views on R&D at GSK, a topic that has been central to his life since he took the top research post close to 2 years ago. During the conversation, Barron talked about changing the culture at GSK, a move that involves several new approaches — one of which involves celebrating their setbacks as they shift resources to the most promising programs in the pipeline. Barron also discussed his new alliances in the Bay Area — including his collaboration pact with Lyell, which we covered here — frankly assesses the pluses and minuses of the UK drug development scene, and talks about his plans for making GSK a much more effective drug developer.

This is one discussion you won’t want to miss. Insider and Enterprise subscribers can log-in to watch the video.

Endpoints Premium

Premium subscription required

Unlock this article along with other benefits by subscribing to one of our paid plans.

Christine Bunt, Robert Langer. Verseau

Armed with Langer tech and $50M, Verseau hails new check­point drugs un­leash­ing macrophages against can­cer

The rising popularity of CD47 has propelled the “don’t-eat-me” signal to household name status in the immuno-oncology world: By blocking that protein, the theory goes, one can stop cancer cells from fooling macrophages. But just as PD-(L)1 merely represents the most fruitful of all checkpoints regulating T cells, Verseau Therapeutics is convinced that CD47 is one of many regulators one can modulate to stir up or tame the immune system.

Mi­rati preps its first look at their KRAS G12C con­tender, and they have to clear a high bar for suc­cess

If you’re a big KRAS G12C fan, mark your calendars for October 28 at 4:20 pm EDT.

That’s when Mirati $MRTX will unveil its first peek at the early clinical data available on MRTX849 in presentations at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics in Boston.

Mirati has been experiencing the full effect of a rival’s initial success at targeting the G12C pocket found on KRAS, offering the biotech some support on the concept they’re after — and biotech fans a race to the top. Amgen made a big splash with its first positive snapshot on lung cancer, but deflated sky-high expectations as it proved harder to find similar benefits in other types of cancers.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 62,500+ biopharma pros reading Endpoints daily — and it's free.