Zaf­gen stakes out a PhI beach­head for its next weight drug as it fights for a come­back

Last sum­mer Zaf­gen $ZFGN ex­pe­ri­enced one of the worst biotech dis­as­ters the in­dus­try wit­nessed for all of last year — the kind of night­mare that CEOs dread. Af­ter the FDA put their lead drug be­lo­ranib on clin­i­cal hold in late 2015 — link­ing it to the death of a pa­tient from a pul­monary em­bolism linked with the ther­a­py — the biotech had lit­tle choice but to kill the pro­gram in Ju­ly and slash its staff af­ter reg­u­la­tors spelled out what they would have to do to qual­i­fy for a mar­ket­ing OK.

Tom Hugh­es

But with its share price dec­i­mat­ed, Zaf­gen still didn’t throw in the tow­el. And now in an ef­fort to make a come­back, Zaf­gen’s team has re­leased Phase I da­ta that shows its sole clin­i­cal drug hope, ZGN-1061, a fol­lowup MetAP2 drug, was able to knock about a pound a week off of obese and over­weight pa­tients for four weeks, with­out any signs of throm­bot­ic risk.

Zaf­gen shares surged 15% on the news Thurs­day evening, in post-mar­ket trad­ing.

Break­ing down the da­ta, pa­tients treat­ed with ZGN-1061 for four weeks lost sig­nif­i­cant­ly more weight rel­a­tive to place­bo-treat­ed pa­tients, drop­ping 4.6 lbs, 2.2 lbs and 3.8 lbs for 0.2 mg, 0.6 mg, and 1.8 mg dos­es, re­spec­tive­ly, com­pared to a 0.51 lb loss for the place­bo arm. And that’s what they were hop­ing to see as they po­si­tion them­selves for a run at obe­si­ty and Type 2 di­a­betes, two of the most dif­fi­cult mass mar­ket con­di­tions any biotech ever tack­led.

That’s not the kind of sud­den and mas­sive weight loss that be­lo­ranib could trig­ger in the first few weeks, CEO Tom Hugh­es con­cedes, but cu­mu­la­tive­ly it’s sig­nif­i­cant­ly bet­ter than the dis­ap­point­ing trio of weight drugs that hit a few years ago. This drug, he em­pha­sized, is on the right track for a Phase I, bless­ed­ly free of any sur­pris­es for the re­searchers in­volved.

“We’ve been work­ing in this area for quite some time,” Hugh­es told me ear­li­er Thurs­day. That gives the team at Zaf­gen a chance to care­ful­ly eval­u­ate the phar­ma­co­ki­net­ic qual­i­ties of  ZGN-1061, tar­get en­gage­ment and the dose ef­fect, con­firm­ing the “good be­hav­ior” of the drug in an ad­mit­ted­ly small num­ber of sub­jects.

Hugh­es was def­i­nite­ly up­beat about the re­sults, but al­so per­haps a lit­tle more sub­dued than in past dis­cus­sions about be­lo­ranib as that drug head­ed through the clin­ic be­fore im­plod­ing in Phase III.

“I don’t know if you can tell by our tone,” he said at one point, “but we are re­al­ly, re­al­ly pleased with the re­sult….It’s good to have a well-be­haved mol­e­cule.”

And how.

Phase I is a rel­a­tive­ly small step in the obe­si­ty/di­a­betes R&D world, with ma­jor de­mands that ul­ti­mate­ly have to be met on safe­ty and ef­fi­ca­cy that have be­dev­iled oth­er de­vel­op­ers over the years and forced in­vestors to di­rect their cash else­where.

Phase II, slat­ed to get un­der­way lat­er this year, will re­cruit about 120 pa­tients with Type 2 di­a­betes, says CMO Den­nis Kim, prob­a­bly look­ing at he­mo­glo­bin A1c lev­els — a clas­sic mea­sure of ef­fi­ca­cy — as the pri­ma­ry end­point. The com­pa­ny still prob­a­bly hasn’t es­tab­lished the low­est most ef­fec­tive dose of the drug, which they should be able to shine a light on as mid-stage da­ta comes through.

Lat­er on, adds Hugh­es, it’s pos­si­ble that Zaf­gen could take on a part­ner as it an­gles for a Phase III. And cer­tain­ly on­ly a ma­jor play­er could ex­pect to mar­ket a drug like this if it even­tu­al­ly wins an OK. But if things con­tin­ue to go the biotech’s way this time, Hugh­es feels that the cap­i­tal will be there for what’s need­ed.

Now it’s time to con­cen­trate on step 2 in their re­hab pro­gram.

 

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?

Pfiz­er gets some en­cour­ag­ing PhI­II news on a fran­chise sav­ior, but is a dos­ing ad­van­tage worth the $295M up­front?

Close to 3 years after Opko tried to defend itself as shares tumbled on the news that its long-acting growth hormone had failed to outperform a placebo, the Pfizer partner $PFE is back. And this time they’re pitching Phase III data that demonstrates their drug is non-inferior — or maybe a tad better — than their well-known but fading standard in the field.
The comparator drug here is Genotropin, which earned a marginal $142 million for Pfizer last year — down 9% from the year before. Approved 24 years ago, biosimilars are now in development that Pfizer would like to stay out in front of.
The new data, says researchers, underscore that a weekly injection of somatrogon performed as well or slightly better than Genotropin (somatropin) in young children with growth hormone deficiency. Investigators tracked height velocity at 10.12 cm/year, edging out the older drug’s 9.78 cm/year. That 0.33 difference may not prove compelling to payers, though, who have been known to overlook dosing advantages in favor of lower costs.
That message may have weighed on the stock reaction this morning, with a 30%-plus hike $OPK giving way to more marginal gains.
Back in late 2016, Opko had to defend itself against a devastating Phase III setback as their initial late-stage trial failed against a sugar pill. Opko later blamed that setback on outliers in the study, though it wasn’t able to expunge the failure.
Pfizer bought into the drug 5 years ago, paying $295 million upfront as then group president Geno Germano touted the drug as the first significant innovation in the growth hormone field in 20 years.
Germano has left the pharma giant, leaving the honors to Pfizer’s chief development officer, Brenda Cooperstone.
“We’re encouraged by these data and look forward to the possibility of bringing this longer-acting therapy to children. If approved, somatrogon could reduce the daily disease burden on children and their caregivers, potentially increasing treatment adherence.”

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As­traZeneca's Farx­i­ga scores FDA nod to cut risk of hos­pi­tal­iza­tion for heart fail­ure in di­a­bet­ics

While the FDA recently spurned an application to allow AstraZeneca’s blockbuster drug Farxiga for type 1 diabetes that cannot be controlled by insulin, citing safety concerns — the US regulator has endorsed the use of the SGLT2 treatment to reduce the risk of hospitalisation for heart failure in patients with type-2 diabetes and established cardiovascular disease or multiple CV risk factors.

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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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.

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.