J&J’s IL-23 star guselkum­ab grabs the spot­light in PhI­II pso­ri­a­sis show­down

J&J has long had high hopes for its an­ti-in­flam­ma­to­ry IL-23 drug guselkum­ab. And to­day in Vi­en­na they de­tailed the first round of Phase III da­ta for se­vere plaque pso­ri­a­sis that ex­plains why.

Philippe Sza­pary, Janssen

In­ves­ti­ga­tors say this drug not on­ly hand­i­ly beat a place­bo, it al­so out­stripped the megablock­buster Hu­mi­ra in key mea­sures of ef­fi­ca­cy. And that will help po­si­tion the phar­ma gi­ant as it starts to line up reg­u­la­to­ry ap­provals for a new ther­a­py that’s like­ly head­ed in­to a heav­i­ly com­pet­i­tive mar­ket.

In the VOY­AGE 1 study, J&J says that the co-pri­ma­ry end­points were met at week 16, with 85.1% of pa­tients re­ceiv­ing guselkum­ab 100 mg at weeks 0 (the start of ther­a­py) and 4 and then every eight weeks achiev­ing cleared (IGA 0) or min­i­mal dis­ease (IGA 1) com­pared with 6.9% of pa­tients re­ceiv­ing place­bo.  Near­ly three-quar­ters of pa­tients re­ceiv­ing guselkum­ab (73.3%) achieved a PASI 90 re­sponse, or near com­plete skin clear­ance, com­pared with 2.9% of pa­tients re­ceiv­ing place­bo.

That’s al­so good news for Mor­phoSys, which part­nered with J&J on the drug.

All ma­jor sec­ondary end­points in VOY­AGE 1 achieved sta­tis­ti­cal sig­nif­i­cance in com­par­isons of guselkum­ab with Hu­mi­ra (adal­i­mum­ab). Here’s the sum­ma­ry:

At week 16, fol­low­ing three in­jec­tions of guselkum­ab and ten in­jec­tions of adal­i­mum­ab, sig­nif­i­cant­ly high­er pro­por­tions of pa­tients re­ceiv­ing guselkum­ab achieved IGA 0/1 and PASI 90 (85.1 per­cent and 73.3 per­cent, re­spec­tive­ly) com­pared with pa­tients re­ceiv­ing adal­i­mum­ab (65.9 per­cent and 49.7 per­cent, re­spec­tive­ly).  At week 24, the pro­por­tion of pa­tients who achieved a PASI 90 re­sponse was sig­nif­i­cant­ly high­er in the guselkum­ab group com­pared with the adal­i­mum­ab group (80.2 per­cent vs. 53.0 per­cent, re­spec­tive­ly).  High­er lev­els of skin clear­ance among the guselkum­ab group con­tin­ued through weeks 24 and 48, with sig­nif­i­cant­ly more pa­tients re­ceiv­ing guselkum­ab achiev­ing IGA 0/1 and PASI 90, as well as mea­sures of full skin clear­ance, as in­di­cat­ed by a 100 per­cent im­prove­ment in PASI score (PASI 100) or an IGA score of 0, com­pared with adal­i­mum­ab.

J&J is look­ing to in­crease its pres­ence in a mar­ket where it’s been build­ing sales for Ste­lara while main­tain­ing an old main­stay, Rem­i­cade, an an­ti-TNF drug like Hu­mi­ra. This new drug is slat­ed to ar­rive as biosim­i­lars for both of the old drugs are an­gling to hit the mar­ket, though Ab­b­Vie has vowed to fight to the bit­ter end over Hu­mi­ra’s patent pro­tec­tion.

“I think (guselkum­ab) ac­tu­al­ly works bet­ter than what we had seen from the da­ta in Phase II,” says Philippe Sza­pary, the VP of im­munol­o­gy clin­i­cal de­vel­op­ment at Janssen, who says both the PASI 90 and clear­ance rates are high­er than the mid-stage re­sults, which may be ex­plained by an ex­tra load­ing dose used in Phase III.

That dif­fer­ence has helped es­tab­lish “good main­te­nance over time” with a rel­a­tive­ly quick on­set for many that could help demon­strate to pa­tients that they’re on the right track.

Even with da­ta from two more late-stage tri­als on track for a lat­er re­lease, Sza­pary says that J&J is on track for reg­u­la­to­ry sub­mis­sions by the end of this year.

“There’s a lot more to come out,” Sza­pary adds, as J&J lays out its case that this drug is bi­o­log­i­cal­ly avail­able to a wide range of pa­tients, from front­line use on to oth­ers.

This fast-mov­ing field has seen plen­ty of dra­ma over the past year. At one point As­traZeneca and Am­gen thought they were on track with bro­dalum­ab, then in­ci­dents of sui­ci­dal ideation drove Am­gen out and per­suad­ed As­traZeneca to sell rights to the drug to a trou­bled Valeant, which won a re­cent pan­el vote.

In the mean­time, Eli Lil­ly made it on­to the mar­ket with Taltz (ix­ek­izum­ab) with No­var­tis out with the first new con­tender, Cosen­tyx. Mer­ck is still in the clin­ic with MK-3222.

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:

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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.

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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.

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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.

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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.

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