Dai­ichi Sankyo 'dis­ap­point­ed' as FDA ex­perts spurn AML drug but vote in fa­vor of rare tu­mor drug

Dai­ichi Sankyo has of­fered up the fresh­est case study of just where the line is drawn on can­cer drugs show­ing in­cre­men­tal — or even ques­tion­able — ben­e­fits, as crit­i­cal in­ter­nal re­views from the FDA trans­lat­ed in­to dif­fer­ing ad­vi­so­ry com­mit­tee opin­ions on two of its pitch­es.

By a 3-8 mar­gin, the on­col­o­gy ex­perts con­vened by the agency shot down the Japan­ese drug­mak­er’s case for its acute myeloid leukemia drug quizar­tinib, hav­ing vot­ed in fa­vor of pex­i­dar­tinib in the morn­ing ses­sion. Pex­i­dar­tinib treats be­nign tu­mors known as symp­to­matic tenosyn­ovial gi­ant cell tu­mor.

De­signed specif­i­cal­ly for FLT3-ITD–pos­i­tive AML, quizar­tinib was her­ald­ed as a sig­nif­i­cant new op­tion for re­frac­to­ry pa­tients who are count­ing their last days. Dai­ichi Sankyo bagged the ty­ro­sine ki­nase in­hibitor in a buy­out of Am­bit Bio­sciences val­ued at $410 mil­lion in 2014. Last Au­gust, the com­pa­ny scored a break­through ther­a­py des­ig­na­tion for it on the back of piv­otal da­ta that showed a 27% over­all sur­vival rate com­pared to 20% in the chemother­a­py arm.

Richard Paz­dur

But ad­comm mem­bers sided with FDA re­view­ers in wor­ry­ing that the re­sults, de­spite be­ing sta­tis­ti­cal­ly sig­nif­i­cant, had to do with im­bal­ances be­tween the drug and chemo co­horts. Com­pared to the chemo arm, the quizar­tinib group had a high­er per­cent­age of pa­tients who went on to re­ceive hematopoi­et­ic stem cell trans­plants, a low­er num­ber of non-treat­ed cas­es, and few­er in­stances of in­com­plete OS da­ta — all point­ing to­ward a po­ten­tial bias.

Richard Paz­dur, the pow­er­ful di­rec­tor of the FDA’s On­col­o­gy Cen­ter of Ex­cel­lence, chimed in at the meet­ing, say­ing he hasn’t come across a re­sult like this in 20 years.

“While we are dis­ap­point­ed by the out­come of to­day’s ODAC vote, we will work close­ly with the FDA as it com­pletes the re­view of our sub­mis­sion,” said An­toine Yver, Dai­ichi Sankyo’s glob­al head of on­col­o­gy R&D.

An­toine Yver

Reg­u­la­tors, who are not oblig­ed to fol­low the ad­comm’s ad­vice but of­ten do, will have un­til Au­gust 25 to de­cide af­ter ex­tend­ing an ear­li­er dead­line to re­view more da­ta. Dai­ichi Sankyo’s loss here could be Astel­las’ and No­var­tis’ gain as they con­tin­ue to carve out a place for Xospa­ta and Ry­dapt, re­spec­tive­ly.

It’s a sharp con­trast with pex­i­dar­tinib, which would be the first non-sur­gi­cal treat­ment for a rare but of­ten de­bil­i­tat­ing con­di­tion in­volv­ing tu­mors in joints and ten­dons.

Here the main con­cern was liv­er tox­i­c­i­ty, a con­cern that had pre­vi­ous­ly cur­tailed en­roll­ment in a Phase III. While ad­comm mem­bers ac­knowl­edged the safe­ty is­sues, the ma­jor­i­ty of them trust­ed a de­cent risk eval­u­a­tion and mit­i­ga­tion strat­e­gy, or REMS, would suf­fi­cient­ly low­er the risks.

Though the FDA al­so raised ques­tions about ef­fi­ca­cy, cit­ing a “high lev­el of miss­ing da­ta at Week 25,” 12 of the ex­perts on the pan­el had no prob­lem en­dors­ing the ben­e­fits over the risks.

“I did not see the lon­gi­tude in the da­ta around 25 weeks and this is why I took more of the con­ser­v­a­tive side,” added one of the 3 who vot­ed no. “I was wor­ried about the ef­fi­ca­cy and qual­i­ty of life da­ta be­yond 25 weeks.”

The PDU­FA date for pex­i­dar­tinib is Au­gust 3.

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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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.

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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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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Eli Lil­ly’s first PhI­II show­down for their $1.6B can­cer drug just flopped — what now?

When Eli Lilly plunked down $1.6 billion in cash to acquire Armo Biosciences a little more than a year ago, the stars seemed aligned in its favor. The jewel in the crown they were buying was pegilodecakin, which had cleared the proof-of-concept stage and was already in a Phase III trial for pancreatic cancer.

And that study just failed.

Lilly reported this morning that their cancer drug flopped on overall survival when added to FOLFOX (folinic acid, 5-FU, oxaliplatin), compared to FOLFOX alone among patients suffering from advanced pancreatic cancer.

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