CEO Matt Kapusta (uniQure)

Look­ing for leg up in he­mo­phil­ia B gene ther­a­py race, uniQure flash­es da­ta that helped lead to $2B CSL deal

In the two-head­ed race to de­vel­op the first gene ther­a­py for he­mo­phil­ia B, uniQure just got a ma­jor leg up.

In a late-break­ing ab­stract at ASH, the com­pa­ny re­leased da­ta from their piv­otal 54-per­son Phase III tri­al, show­ing that it in­creased lev­els of Fac­tor IX from be­low 2% of nor­mal to 37% of nor­mal af­ter 26 weeks. Al­though the com­pa­ny will still need to col­lect 52-week da­ta, the lev­els come in above what Pfiz­er has shown in ear­ly stud­ies for their ri­val gene ther­a­py and at or above what an­a­lysts sug­gest­ed would be need­ed to show ef­fi­ca­cy.

In an in­ter­view, CEO Matt Ka­pus­ta de­clined to dis­close what num­ber they had told the FDA they were go­ing for, but said they viewed the re­sult as an un­mit­i­gat­ed suc­cess.

“I think [it] rep­re­sents func­tion­al­ly cu­ra­tive lev­els for these pa­tients,” Ka­pus­ta told End­points News. “So it’s very ex­cit­ing.”

UniQure’s stock $QURE was up 6% on the news, from $42.76 to $45.50.

The sec­ondary end­points al­so proved pos­i­tive but not per­fect: 72% of pa­tients record­ing no bleed­ing in­ci­dents af­ter ad­min­is­tra­tion, while av­er­age us­age of stan­dard Fac­tor IX re­place­ment ther­a­py fell by 96%.

The da­ta pro­vid­ed pub­lic val­i­da­tion for CSL Behring and their sur­prise de­ci­sion ear­li­er this year to pur­chase the gene ther­a­py in a mile­stone-heavy deal up to $2 bil­lion. UniQure said at the time that CSL had al­ready seen pri­vate in­ter­im da­ta pri­or to pur­chas­ing the ther­a­py. Ka­pus­ta said CSL saw 12-week da­ta.

An­a­lysts ar­gued pri­or to the read­out that any in­crease to at least 10% of nor­mal should yield clin­i­cal ef­fects. Stifel’s Melis­sa Scott ar­gued “any­thing above 20%” would be ef­fec­tive. SVB Leerink’s Joseph Schwartz set the tar­get range be­tween 30 to 50%.

Stifels’ Paul Mat­ties praised the Phase III da­ta as “en­cour­ag­ing, though not sur­pris­ing.”

Pfiz­er’s gene ther­a­py, orig­i­nal­ly de­vel­oped with Spark Ther­a­peu­tics and now in its own Phase III, showed Fac­tor IX rates at 23% af­ter one year in a 15-per­son tri­al. Al­though the Big Phar­ma start­ed dos­ing first, an­a­lysts ex­pect­ed uniQure to move faster.

Side ef­fects were min­i­mal. The most com­mon events in­clud­ed height­ened liv­er en­zymes, in­fu­sion re­lat­ed re­ac­tions, headache, and flu-like symp­toms. Be­tween 13% and 15% of pa­tients ex­pe­ri­enced each.

The com­pa­ny al­so not­ed that pa­tients who had pre-ex­ist­ing an­ti­bod­ies to ade­n­ovirus per­formed no worse on the gene ther­a­py, which is de­liv­ered through an ade­no-as­so­ci­at­ed vi­ral vec­tor.

The big ques­tion will now be how much da­ta the FDA would re­quire for ap­proval. uniQure had orig­i­nal­ly ap­peared like­ly to file a BLA in 2021, but the en­tire he­mo­phil­ia gene ther­a­py was up­end­ed ear­li­er this Au­gust af­ter the agency hand­ed Bio­Marin a CRL on their he­mo­phil­ia A gene ther­a­py, de­mand­ing more da­ta on dura­bil­i­ty.

Ka­pus­ta said Bio­Marin’s prob­lems were unique to Bio­Marin, point­ing to da­ta sug­gest­ing their gene ther­a­py’s ef­fects waned over time and the fact that the biotech chose to go for ap­proval on just 26-week da­ta from a sub­set of pa­tients in their piv­otal tri­al.

Still, he ac­knowl­edged that the feed­back they re­ceived has shift­ed in re­cent months, with im­pli­ca­tions for their lead ther­a­py. The agency “re­cent­ly” asked  uniQure to make bleed­ing in­ci­dents a co-pri­ma­ry end­point of the tri­al, Ka­puto said, along­side Fac­tor IX lev­els.

That re­quire­ment, he ar­gued, will al­le­vi­ate con­cerns about their pa­tient’s Fac­tor IX lev­els, as it shows the ther­a­py’s re­al world im­pact. The com­pa­ny will have to show non-in­fe­ri­or­i­ty on bleed­ing to the Fac­tor IX re­place­ment ther­a­py that pa­tients took pri­or to re­ceiv­ing the gene ther­a­py.

“I think the da­ta speaks for it­self,” he said. ” The gold stan­dard is bleed­ing.”

Ka­pus­ta said they will meet with the FDA to dis­cuss a BLA af­ter con­duct­ing their last 52-week fol­low-up on their last pa­tient next March.

“And that pro­vides da­ta to sup­port a tra­di­tion­al ap­proval in he­mo­phil­ia treat­ment,” he said.

Biogen CEO Michel Vounatsos (via Getty Images)

With ad­u­canum­ab caught on a cliff, Bio­gen’s Michel Vounatsos bets bil­lions on an­oth­er high-risk neu­ro play

With its FDA pitch on the Alzheimer’s drug aducanumab hanging perilously close to disaster, Biogen is rolling the dice on a $3.1 billion deal that brings in commercial rights to one of the other spotlight neuro drugs in late-stage development — after it already failed its first Phase III.

The big biotech has turned to Sage Therapeutics for its latest deal, close to a year after the crushing failure of Sage-217, now dubbed zuranolone, in the MOUNTAIN study.

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Jason Kelly, Ginkgo Bioworks CEO (Kyle Grillot/Bloomberg via Getty Images)

Af­ter Ko­dak de­ba­cle, US lends $1.1B to a syn­thet­ic bi­ol­o­gy com­pa­ny and their big Covid-19, mR­NA plans

In mid-August, as Kodak’s $765 million government-backed push into drug manufacturing slowly fell apart in national headlines, Ginkgo Bioworks CEO Jason Kelly got a message from his company’s government liaison: HHS wanted to know if they, too, might want a loan.

The government’s decision to lend Kodak three quarters of a billion dollars raised eyebrows because Kodak had never made drugs before. But Ginkgo, while not a manufacturing company, had spent the last decade refining new ways to produce materials inside cells and building automated facilities across Boston.

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Vivek Ramaswamy (Jeff Rumans/JPM 2020)

Urovan­t's lead drug dis­ap­points in mid-stage study as first big FDA de­ci­sion looms

Just as Urovant gets ready for its first big FDA decision on vibegron, the drug has flopped in what would’ve been a follow-on indication.

In a Phase IIa trial involving women with abdominal pain due to irritable bowel syndrome, vibegron failed to meet the bar on improving “average worst abdominal pain” over 12 weeks, compared to placebo, among IBS-D patients.

There were actually slightly more responders in the placebo group than in the drug arm, with only 40.9% of those randomized to vigebron achieving at least a 30% decrease in “worst abdominal pain” in the past 24 hours. The trial enrolled 222 women but only 189 completed the study.

Gen­mab ax­es an ADC de­vel­op­ment pro­gram af­ter the da­ta fail to im­press

Genmab $GMAB has opted to ax one of its antibody-drug conjugates after watching it flop in the clinic.

The Danish biotech reported Tuesday that it decided to kill their program for enapotamab vedotin after the data gathered from expansion cohorts failed to measure up. According to the company:

While enapotamab vedotin has shown some evidence of clinical activity, this was not optimized by different dose schedules and/or predictive biomarkers. Accordingly, the data from the expansion cohorts did not meet Genmab’s stringent criteria for proof-of-concept.

Vas Narasimhan, Novartis CEO (Jason Alden/Bloomberg via Getty Images)

Vas Narasimhan's 'Wild Card' drugs: No­var­tis CEO high­lights po­ten­tial jack­pots, as well as late-stage stars, in R&D pre­sen­ta­tion

Novartis is always one of the industry’s biggest R&D spenders. As they often do toward the end of each year, company execs are highlighting the drugs they expect will most likely be winners in 2021.

And they’re also dreaming about some potential big-time lottery tickets.

As part of its annual investor presentation Tuesday, where the company allows investors and analysts to virtually schmooze with the bigwigs, Novartis CEO Vas Narasimhan will outline what he thinks are the pharma’s “Wild Cards.” The slate of five experimental drugs are those that Novartis hopes can be high-risk, high-reward entrants into the market over the next half-decade or so, and cover a wide range of indications.

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The ad­u­canum­ab co­nun­drum: The PhI­II failed a clear reg­u­la­to­ry stan­dard, but no one is cer­tain what that means any­more at the FDA

Eighteen days ago, virtually all of the outside experts on an FDA adcomm got together to mug the agency’s Billy Dunn and the Biogen team when they presented their upbeat assessment on aducanumab. But here we are, more than 2 weeks later, and the ongoing debate over that Alzheimer’s drug’s fate continues unabated.

Instead of simply ruling out any chance of an approval, the logical conclusion based on what we heard during that session, a series of questionable approvals that preceded the controversy over the agency’s recent EUA decisions has come back to haunt the FDA, where the power of precedent is leaving an opening some experts believe can still be exploited by the big biotech.

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John Maraganore, Alnylam CEO (Scott Eisen/Bloomberg via Getty Images)

Al­ny­lam gets the green light from the FDA for drug #3 — and CEO John Maraganore is ready to roll

Score another early win at the FDA for Alnylam.

The FDA put out word today that the agency has approved its third drug, lumasiran, for primary hyperoxaluria type 1, better known as PH1. The news comes just 4 days after the European Commission took the lead in offering a green light.

An ultra rare genetic condition, Alnylam CEO John Maraganore says there are only some 1,000 to 1,700 patients in the US and Europe at any particular point. The patients, mostly kids, suffer from an overproduction of oxalate in the liver that spurs the development of kidney stones, right through to end stage kidney disease.

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Bob Nelsen (Photo by Michael Kovac/Getty Images)

Bob Nelsen rais­es $800M and re­cruits a star-stud­ded board to build the 'Fox­con­n' of biotech

Bob Nelsen spent his pandemic spring in his Seattle home, talking on the phone with Luciana Borio, the scientist who used to run pandemic preparedness on the National Security Council, and fuming with her about the dire state of American manufacturing.

Companies were rushing to develop vaccines and antibodies for the new virus, but even if they succeeded, there was no immediate supply chain or infrastructure to mass-produce them in a way that could make a dent in the outbreak.

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Am­gen sev­ers 14-year Cy­to­ki­net­ics part­ner­ship, bail­ing on ome­cam­tiv af­ter mixed PhI­II re­sults

Amgen is shrugging off a 14-year development alliance and the tens of millions of dollars spent to develop a new heart drug at Cytokinetics after a Phase III trial turned up weak data — leaving Cytokinetics to soldier on alone.

Omecamtiv mecarbil technically worked, meeting the primary composite endpoint in the Phase III GALACTIC-HF study. But it missed a key secondary endpoint, which analysts had been following as a key marker for success — reduction of cardiovascular (CV) death. While Cytokinetics celebrated the results, its stock tanked 43% upon the news, and analysts warned of an uncertain path ahead. Now, Amgen wants out.