Sh­iono­gi cel­e­brates an­tibi­ot­ic win in pneu­mo­nia just ahead of its date with FDA reg­u­la­tors

Just weeks be­fore Sh­iono­gi is sched­uled to hear back from the FDA on treat­ing com­pli­cat­ed uri­nary tract in­fec­tions with its an­tibi­ot­ic, the Japan­ese phar­ma has an­oth­er slate of pos­i­tive da­ta on a dif­fer­ent in­di­ca­tion to share.

In­ves­ti­ga­tors laid out the full num­bers on ce­fide­ro­col in adults with noso­co­mi­al pneu­mo­nia caused by gram-neg­a­tive pathogens — a par­tic­u­lar­ly tough to beat con­di­tion for hos­pi­tal­ized pa­tients, giv­en its mul­ti­ple re­sis­tance mech­a­nisms. In a Phase III, the drug ap­peared non-in­fe­ri­or to high-dose meropen­em in all-cause mor­tal­i­ty af­ter two weeks of treat­ment.

At that time point, 12.4% of the mod­i­fied in­tent-to-treat pop­u­la­tion who re­ceived ce­fide­ro­col (18/145) died, com­pared to 11.6% in the meropen­em group (17/146). In a small­er sub­set of pa­tients who are mi­cro­bi­o­log­i­cal­ly evalu­able, ACM was 12.4% for ce­fide­ro­col and 13% for meropen­em.

Den Na­ga­ta Sh­iono­gi

“In this tri­al, near­ly 60 per­cent of pa­tients were ven­ti­lat­ed and ap­prox­i­mate­ly 33 per­cent ex­pe­ri­enced treat­ment fail­ure of pri­or ther­a­py,” said Sh­iono­gi CMO Tsu­tae “Den” Na­ga­ta. “Re­cent­ly, sev­er­al new an­tibi­otics have been in­tro­duced to ad­dress some car­bapen­em-re­sis­tant in­fec­tions, but they do not ad­dress all re­sis­tant Gram-neg­a­tive pathogens. Clin­i­cians are in ur­gent need of nov­el ther­a­peu­tic ap­proach­es to over­come the mul­ti­ple re­sis­tance mech­a­nisms that make these strains so dif­fi­cult to treat.”

A mem­ber of the cephalosporin class, ce­fide­ro­col is de­signed to bind to fer­ric iron, there­by sneak­ing through the out­er mem­brane of bac­te­r­i­al cells via the iron trans­porters and punch­ing holes.

The drug has been des­ig­nat­ed as a qual­i­fied in­fec­tious dis­ease prod­uct (QIDP) by the FDA, with a PDU­FA date on No­vem­ber 14, 2019. In its lat­est pipeline roundup, the com­pa­ny not­ed that ce­fide­ro­col is be­ing po­si­tioned for cUTIs in the US and a much broad­er la­bel — name­ly mul­tidrug-re­sis­tant gram-neg­a­tive bac­te­r­i­al in­fec­tions — in Eu­rope. Though it had ini­tial­ly been ac­cept­ed in­to the EMA’s ac­cel­er­at­ed ap­proval pro­gram, CHMP reg­u­la­tors pulled it out of that track in Ju­ly.

With noso­co­mi­al pneu­mo­nia, Sh­iono­gi was tak­ing on a tough dis­ease that re­cent­ly tripped up Polyphor due to con­cerns about acute kid­ney in­jury on its drug — the lat­est cau­tion­ary tale in a fail­ure-rid­den an­tibi­otics world.

So­cial im­age: Sh­iono­gi, Hi­romit­su Mo­ri­mo­to via flickr


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.
The oral TKI, designed to zero in on HER2 with a bonus for penetrating the blood brain barrier, delivered a 46% hazard ratio — reduction in risk of disease progression or death — when combined with Herceptin and Xeloda compared to the branded combo alone. That was the primary endpoint. And then two key secondaries followed, starting with a 34% reduction in risk of death alone with a p value for overall survival that hit an approval worthy p=0.0048. There was a more dramatic 52% HR among almost half of the patients who had a brain metastasis at the time of the trial, which some of the analysts see as a key to market success.
We’ll have to wait until the San Antonio Breast Cancer Symposium for the breakdown on just how many months of PFS and OS Seattle Genetics is talking about.
While the researchers were after drug resistant third-line cases in the study, where regulators are generous in allowing high levels of toxicity for dying patients, the safety profile is still key here to the drug’s competitive position on the market. By steering clear of EGFR-linked toxicity, the company is looking for a better safety profile. And while the triplet led to a 5.7% drop out rate due to adverse events, compared to 3% for the double, analysts have been scoring this one much better than Nerlynx or Tykerb.

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?

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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The FDA will hus­tle up an ex­pe­dit­ed re­view for As­traZeneca’s next shot at a block­buster can­cer drug fran­chise

AstraZeneca paid a hefty price to partner with Daiichi Sankyo on their experimental antibody drug conjugate for HER2 positive breast cancer. And they’ve been rewarded with a fast ride through the FDA, with a straight shot at creating another blockbuster oncology franchise.

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Sean Parker, AP

Sean Park­er helps cre­ate a CRISPRed cell ther­a­py 2.0 play — and he’s got a high-pro­file set of lead­ers on the team

You can rack up one more high-profile debut effort in the wave of activity forming around cell therapy 2.0. It’s another appealing Bay Area group that’s attracted some of the top hands in the business to a multi-year effort to create a breakthrough. And they have $85 million in hand to make that first big step to the clinic.

Today it’s Ken Drazan and the team at South San Francisco-based ArsenalBio that are coming from behind the curtain for a public bow, backed by billionaire Sean Parker and a collection of investors that includes Beth Seidenberg’s new venture investment operation based in LA.
Drazan — a J&J Innovation vet with a long record of entrepreneurial endeavors — exited the stage in 2018 when his last mission ended as he stepped aside as president of Grail. It wasn’t long, though, before he was helping out with a business plan for ArsenalBio that revolved around the work of a large group of interconnected scientists supported by the Parker Institute for Cancer Immunology.

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CSL ac­cus­es ri­val Pharm­ing of par­tic­i­pat­ing in a scheme to rip off IP on HAE while re­cruit­ing se­nior R&D staffer

Pharming has landed in the middle of a legal donnybrook after recruiting a senior executive from a rival R&D team at CSL. The Australian pharma giant slapped Pharming with a lawsuit alleging that the Dutch biotech’s new employee, Joseph Chiao, looted a large cache of proprietary documents as he hit the exit. And they want it all back.
Federal Judge Juan Sanchez in the Eastern District Pennsylvania court issued an injunction on Tuesday prohibiting Chiao from doing any work on HAE or primary immune deficiency in his new job and demanding that he return any material from CSL that he may have in his possession. And he wants Pharming to tell its employees not to ask for any information on the forbidden topics.
For its part, Pharming fired off an indignant response this morning denying any involvement in extracting any kind of IP from CSL, adding that it’s cooperating in the internal probe that CSL has underway.

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