Seat­tle Ge­net­ics gets a PhI­II win for Ad­cetris, but shares slide as frets linger

Seat­tle Ge­net­ics $SGEN has had a rough Q2 as its lead ex­per­i­men­tal ther­a­py was put back on hold, forc­ing in­ves­ti­ga­tors to scrap Phase III short­ly af­ter the biotech had to drop a deal with Im­munomedics. But it’s wind­ing up the quar­ter with a ma­jor win in its fa­vor, post­ing a hit in its close­ly-watched Ech­e­lon-1 study for front­line Hodgkin lym­phoma.

The big biotech says that its flag­ship ther­a­py, Ad­cetris, com­bined with a trio of stan­dard drugs beat a 4-drug main­stay cock­tail ther­a­py in front­line Hodgkin dis­ease for mod­i­fied pro­gres­sion-free sur­vival over a lengthy two-year stretch. The Ad­cetris pack­age ex­clud­ed bleomycin, which has been linked to a high­er rate of lung tox­i­c­i­ty and was used in the 4-drug com­bo con­trol.

Clay Sie­gall

Com­pa­ny ex­ecs tell me that they’re prep­ping an FDA ap­pli­ca­tion an­tic­i­pat­ed for lat­er this year. Seat­tle Ge­net­ics con­trols the US and Cana­di­an mar­kets for Ad­cetris, with its part­ner Take­da tak­ing on the rest of the world.

An­a­lysts have been watch­ing this key cat­a­lyst close­ly, look­ing to see if Seat­tle Ge­net­ics has a good chance of sig­nif­i­cant­ly ex­pand­ing its rev­enue from Ad­cetris. The an­swer to that would ap­pear to be a con­di­tion­al yes, based on the biotech’s top-line da­ta.

The Ad­cetris com­bo hit a two-year mod­i­fied PFS rate of 82.1% com­pared to 77.2% in the con­trol arm — a 4.9 point, or 6%, im­prove­ment. That’s sta­tis­ti­cal­ly sig­nif­i­cant, but not the wider, dou­ble-dig­it mar­gin that the bulls have been look­ing for, ac­cord­ing to a re­cent deep dive on this sub­ject from Leerink.

An­a­lysts there have not­ed that with­out a 10%-plus mar­gin in its fa­vor, pay­ers may just stick with the cheap­er stan­dard. The dif­fer­ence could amount to hun­dreds of mil­lions of dol­lars for Seat­tle Ge­net­ics by 2025.

In­vestors weren’t hap­py with the num­bers. Seat­tle Ge­net­ics’ shares dropped 11% as the da­ta sank in on Wall Street. Some of the ear­ly re­ac­tions on Twit­ter were al­so crit­i­cal.

You al­ways pre­fer a bet­ter re­sponse, Seat­tle Ge­net­ics CEO Clay Sie­gall told me in a pre­view of the an­nounce­ment. But this marks a clear win for pa­tients and a plus for the com­pa­ny as Sie­gall re­mains de­ter­mined to make Ad­cetris a bil­lion dol­lar-plus block­buster.

“We did a pret­ty au­da­cious tri­al,” Sie­gall says. “Peo­ple said you’re try­ing to build on some­thing that al­ready looks pret­ty good…There wasn’t a lot of head­room.”

Ad­cetris and the com­bo de­liv­ered a 23% re­duc­tion in risk of pro­gres­sion, he says, build­ing the num­ber of durable re­spons­es among pa­tients who are of­ten di­ag­nosed in their twen­ties and thir­ties. In ad­di­tion, he says, doc­tors clear­ly want to elim­i­nate bleomycin and the risk of lung tox­i­c­i­ty, of­fer­ing an­oth­er ad­van­tage for Ad­cetris.

Seat­tle Ge­net­ics added that an in­ter­im look at over­all sur­vival rates — the sec­ondary to watch — ap­peared to be “trend­ing” in its fa­vor at the in­ter­im point. That’s not un­ex­pect­ed. It will prob­a­bly take 4 years to reach a con­clu­sion on OS, says the CEO, in this pop­u­la­tion.

There’s al­so like­ly to be con­tin­ued chat­ter about in­ves­ti­ga­tors’ use of “mod­i­fied” PFS in the study.

Rather than stick with track­ing the time un­til dis­ease pro­gres­sion, re­searchers mod­i­fied the end­point to in­clude the use of an ad­di­tion­al ther­a­py for pa­tients who had a “cer­tain lack of re­sponse,” says the CEO, who added that that is a sim­plis­tic de­f­i­n­i­tion. If ap­proved, says Sie­gall, this would be Ad­cetris’ 5th OK, with ear­li­er ex­pan­sions help­ing to con­tin­ue to widen the mar­ket for their drug.

Sie­gall al­so says that the pipeline at Seat­tle Ge­net­ics con­tin­ues to of­fer some stel­lar prospects for beef­ing up its port­fo­lio of mar­ket­ed drugs. The biotech re­mains ready to do new deals, he says, but on­ly on an ‘as want­ed’ ba­sis as op­posed to an ‘as need­ed’ ba­sis.

“We think Ad­cetris has an ex­cel­lent chance of be­ing a bil­lion-dol­lar drug in the US,” says the CEO. The next year will pro­vide some in­sights in­to just how like­ly that is.

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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