Now with ac­tu­al da­ta in hand, Cel­gene touts an ear­ly re­sponse for Crohn’s drug mon­gersen

Scott Smith, Cel­gene

A month af­ter post­ing an un­der­whelm­ing top-line as­sess­ment of a Phase Ib study of its close­ly watched Crohn’s drug mon­gersen (GED-0301) for Crohn’s dis­ease, Cel­gene post­ed an up­date Sun­day evening that in­clud­ed a pos­i­tive snap­shot of the ac­tu­al da­ta.

In­ves­ti­ga­tors for the study say they were able to track a quick re­sponse to the drug, which Cel­gene paid a whop­ping $710 mil­lion in cash to in-li­cense the drug for Crohn’s. The re­searchers tracked the im­pact of 160 mg dos­es of the drug on en­do­scop­ic re­sponse and clin­i­cal re­mis­sion among 63 pa­tients with ac­tive Crohn’s dis­ease over short pe­ri­ods stretch­ing from 4 to 8 to 12 weeks. And they say the 12-week group has re­spond­ed with the most im­pres­sive re­sults — though some might ob­ject to what qual­i­fies as im­pres­sive at this stage of the game for such an ex­pen­sive ther­a­py.

The da­ta:

Clin­i­cal im­prove­ment was seen by week 2, and clin­i­cal re­sponse (CDAI de­crease ≥100) and re­mis­sion (CDAI <150) rates were high­est in the 12-week treat­ment group at 67 and 48 per­cent re­spec­tive­ly, at week 12. The mean CDAI re­duc­tion from base­line at week 12 in the 12-week treat­ment group was 133 points. Of the pa­tients with evalu­able en­do­scopies at week 12 (n=52), 37 per­cent had an en­do­scop­ic re­sponse (≥25 per­cent re­duc­tion in SES-CD score from base­line), with no mean­ing­ful dif­fer­ence across treat­ment groups. In ad­di­tion, of those pa­tients with greater en­do­scop­ic dis­ease ac­tiv­i­ty at base­line (SES-CD score of >12; n=16), 63 per­cent ex­hib­it­ed a re­duc­tion ≥25 per­cent in SES-CD score and 31 per­cent had a re­duc­tion of ≥50 per­cent.

The in­ves­ti­ga­tors tout­ed the re­sults be­ing post­ed at Unit­ed Eu­ro­pean Gas­troen­terol­o­gy Week in Vi­en­na as ev­i­dence of the kind of ef­fi­ca­cy that Cel­gene was look­ing for. An­a­lysts con­cen­trat­ed on that re­sponse rate and whether it qual­i­fies as the kind of re­sult they were look­ing for. And they can be a tough crowd.

Baird’s Bri­an Sko­r­ney gave a thumbs up to 48% re­mis­sion rate, but was unim­pressed by the 37% en­do­scop­ic re­sponse score. His bot­tom line:

This da­ta ap­pears to be more promis­ing than we ex­pect­ed but it is un­like­ly to dri­ve a ma­te­r­i­al in­crease in con­fi­dence. The en­doscopy re­sults fall short of what we have seen from oth­er stud­ies but the CDAI re­spons­es do ap­pear in line with oth­er agents.

Like­wise, Leerink’s Ge­of­frey Porges saw the po­ten­tial here for block­buster sales of $1.3 bil­lion in 2023 with the drug a like­ly win­ner on front­line ap­proval sta­tus. But there’s noth­ing here that sug­gests an out-of-the-park home run hit. And Cred­it Su­isse cau­tions that this is still ear­ly da­ta from a small study. Doc­tors don’t usu­al­ly do en­do­scopies at 12 weeks and in­ves­ti­ga­tors were re­al­ly look­ing for signs of ac­tiv­i­ty.

In­vestors liked the sounds of that, dri­ving up Cel­gene’s shares by 1.3% Mon­day af­ter­noon.

Add it all up and the drug still looks promis­ing though the ju­ry is def­i­nite­ly still out on what kind of mar­ket awaits GED-0301.

High­light­ed as a key pro­gram in its at­tempt to build a fran­chise for in­flam­ma­tion and im­munol­o­gy, GED-0301 is one of the com­pa­ny’s biggest ex­per­i­men­tal as­sets in the pipeline of the big biotech, which has struck a se­ries of bold deals to build its port­fo­lio of ex­per­i­men­tal ther­a­pies.  The drug is de­signed to slice Smad7 pro­tein lev­els. Spik­ing lev­els of Smad7 in­ter­fere with TGF-β1 an­ti-in­flam­ma­to­ry path­ways in the gut, spurring in­flam­ma­tion.

Cel­gene, though, was clear­ly hap­py to praise the re­sults.

“We are en­cour­aged that oral GED-0301 showed both mean­ing­ful en­do­scop­ic im­prove­ment and clin­i­cal re­mis­sion at an ear­ly time point in this study,” said Scott Smith, pres­i­dent of Cel­gene In­flam­ma­tion & Im­munol­o­gy, in a state­ment. “The fact that this study in­clud­ed near­ly 50 per­cent bi­o­log­ic-ex­pe­ri­enced pa­tients fur­ther re­flects the po­ten­tial of GED-0301 as a nov­el ap­proach for pa­tients with Crohn’s dis­ease search­ing for al­ter­na­tives.”

The big biotech al­so post­ed some up­dat­ed ozan­i­mod da­ta from a mid-stage pro­gram on ul­cer­a­tive col­i­tis, not­ing some fresh signs of ef­fi­ca­cy from the ex­ten­sion re­sults. The added da­ta were al­so re­leased in Vi­en­na.

Adap­tive De­sign Meth­ods Of­fer Rapid, Seam­less Tran­si­tion Be­tween Study Phas­es in Rare Can­cer Tri­als

Rare cancers account for 22 percent of cancer diagnoses worldwide, yet there is no universally accepted definition for a “rare” cancer. Moreover, with the evolution of genomics and associated changes in categorizing tumors, some common cancers are now characterized into groups of rare cancers, each with a unique implication for patient management and therapy.

Adaptive designs, which allow for prospectively planned modifications to study design based on accumulating data from subjects in the trial, can be used to optimize rare oncology trials (see Figure 1). Adaptive design studies may include multiple cohorts and multiple tumor types. In addition, numerous adaptation methods may be used in a single trial and may facilitate a more rapid, seamless transition between study phases.

Marianne De Backer (L) and Jeff Hatfield

Bay­er nabs star biotech Vi­vid­ion with a $2B buy­out and an ‘arms-length’ pact, pulling a part­ner out of the IPO con­ga line

Vividion is canceling that IPO it filed. Instead of following the industry-wide migration to Nasdaq, the biotech that has captured considerable attention for its still-preclinical work finding cryptic pockets to bind to on proteins is going to work for Bayer now.

The pharma giant is putting out word today that it has bought out Vividion for $1.5 billion in cash and another half-billion dollars in milestones.

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Josh Hoffman, outgoing Zymergen CEO (Zymergen)

UP­DAT­ED: Syn­bio uni­corn Zymer­gen jet­ti­sons found­ing CEO, cuts guid­ance as cus­tomers re­port lead prod­uct does­n't work

Zymergen, just months off a $500 million IPO that put the synthetic bio firm in rarified air, has now ejected its founding CEO and downgraded its revenue forecasts after customers reported its lead film product doesn’t work as advertised, the company said Tuesday afternoon.

CEO Josh Hoffman will leave his role and sacrifice his board seat immediately in favor of Jay Flatley, the former CEO of Illumina who will take the lead role on an interim basis as the company conducts a search for its next leader.

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Tadataka Yamada (Photographer: Kiyoshi Ota/Bloomberg via Getty Images)

Sci­ence pi­o­neer, phar­ma re­search chief, glob­al health ad­vo­cate and biotech en­tre­pre­neur Tadata­ka ‘Tachi’ Ya­ma­da has died

Tadataka Yamada, a towering physician-scientist who made his name in academia before transforming drug development at GlaxoSmithKline and developing vaccines for malaria and meningitis at the Gates Foundation, died unexpectedly of natural causes at his home in Seattle Wednesday morning.

He was 76. Frazier Healthcare Partners’ David Socks confirmed his death.

Known widely by the mononym “Tachi,” Yamada had a globetrotting career and arrived in industry relatively late in life. A 2004 Independent article noted GSK had asked Yamada to stay on beyond his approaching 60th birthday, the company’s usual retirement age. Yamada would continue working for the next 17 years, steering the Gates Foundation’s global health division for 6 years, funding Jim Wilson’s gene therapy work when few would touch it, launching Takeda Vaccines and co-founding a series of high-profile biotechs.

UK re-in­ves­ti­gates Pfiz­er's eye-pop­ping price goug­ing on an epilep­sy drug

When a drugmaker raises the price of a drug in the US by more than 2,000% overnight, and without any particular reason for that increase, nothing typically happens to the company. No fines, no court orders, just business as usual.

Martin Shkreli’s decades-old anti-parasitic drug Daraprim was the perfect example — massive price spike on an old drug, lots of media attention, public outcry, congressional committees dragging his former company through multiple hearings, and at the end of it? Nothing happened to the price or the company (until generic competition came).

Thomas Lingelbach, Valneva CEO

A small vac­cine de­vel­op­er fa­vored by the UK gov­ern­ment in Covid-19 touts a PhI­II first in chikun­gun­ya

Before Valneva garnered the favor of the UK government as a potential supplier of Covid-19 vaccines, the French biotech prided itself on being the first company to bring a chikungunya vaccine into Phase III.

It now has positive pivotal results to back up the breakthrough therapy designation the FDA granted just weeks ago.

There are currently no approved jabs to prevent chikungunya virus infection despite decades of R&D efforts, a fact that underscores just how arduous traditional vaccine development can be, particularly for neglected tropical disease. In a absence of a major commercial market, the US government and NGOs such as CEPI have deployed various grants and incentives to spur on a small crew of academics and industry players, with Merck, via its acquisition of Themis, claiming a spot in that race.

Covid-19 roundup: Pfiz­er im­pos­es vac­cine man­date for US work­ers; WHO calls for mora­to­ri­um on boost­ers, while some coun­tries make plans any­way — re­port

As the US struggles to keep pace with the fast-spreading Delta variant, big companies like Walmart and Disney are imposing vaccine mandates for some workers. It may come as no surprise that Pfizer — the Big Pharma behind the US’ first authorized Covid-19 vaccine — is joining them.

Pfizer will start requiring all US employees and contractors to get vaccinated, or participate in weekly Covid-19 testing, spokesperson Pamela Eisele told Reuters. Workers outside the US are strongly urged to get a vaccine if they can, according to the report. And those with medical conditions or religious objections can seek accommodations.

Tien Lee, Aardvark Therapeutics CEO

Emerg­ing from stealth mode, Aard­vark rounds up enough cash to put its lead drug through Prad­er-Willi PhII

When Aardvark Therapeutics CEO Tien Lee started his work on the biotech’s lead candidate, appetite suppression was the goal for the small molecule.  Soon after, his team started to see added benefits with lower blood glucose levels and anti-inflammatory activity. On the tail end of that, the company has emerged from stealth mode and announced today that they’ve raised enough cash in the B round to cover mid-stage development work.

Zymergen co-founders Zach Serber, Josh Hoffman, and Jed Dean (Zymergen via website)

Zymer­gen's sud­den im­plo­sion shocked biotech. A lin­ger­ing loan could make things even worse

As former synbio unicorn Zymergen picks up the pieces from its spectacular implosion Tuesday, an outstanding loan from Perceptive Advisors — the only blue-chip biotech crossover investor to touch Zymergen’s fundraising efforts — could make the situation worse, according to public documents.

In December 2019, more than a year before Zymergen filed for what would eventually become a $500 million IPO, the “biofacturing” firm signed a $100 million credit facility with Perceptive to help supplement the nearly $700 million the company had raised across four VC rounds.