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.

The DCT-OS: A Tech­nol­o­gy-first Op­er­at­ing Sys­tem - En­abling Clin­i­cal Tri­als

As technology-enabled clinical research becomes the new normal, an integrated decentralized clinical trial operating system can ensure quality, deliver consistency and improve the patient experience.

The increasing availability of COVID-19 vaccines has many of us looking forward to a time when everyday things return to a state of normal. Schools and teachers are returning to classrooms, offices and small businesses are reopening, and there’s a palpable sense of optimism that the often-awkward adjustments we’ve all made personally and professionally in the last year are behind us, never to return. In the world of clinical research, however, some pandemic-necessitated adjustments are proving to be more than emergency stopgap measures to ensure trial continuity — and numerous decentralized clinical trial (DCT) tools and methodologies employed within the last year are likely here to stay as part of biopharma’s new normal.

Onno van de Stolpe, Galapagos CEO (Thierry Roge/Belga Mag/AFP via Getty Images)

Gala­pa­gos chops in­to their pipeline, drop­ping core fields and re­or­ga­niz­ing R&D as the BD team hunts for some­thing 'trans­for­ma­tive'

Just 5 months after Gilead gutted its rich partnership with Galapagos following a bitter setback at the FDA, the Belgian biotech is hunkering down and chopping the pipeline in an effort to conserve cash while their BD team pursues a mission to find a “transformative” deal for the company.

The filgotinib disaster didn’t warrant a mention as Galapagos laid out its Darwinian restructuring plans. Forced to make choices, the company is ditching its IPF molecule ’1205, while moving ahead with a Phase II IPF study for its chitinase inhibitor ’4617.

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An­oth­er failed tri­al for Or­p­hazyme's 'pipeline-in-a-pro­duc­t' leaves shad­ow on drug's fu­ture

The tumultuous ride for Orphazyme continued on Friday as the company announced that a pivotal trial for its lead drug arimoclomol failed yet again, this time in the treatment of ALS, seeding doubt in a drug that had recently been cleared by the FDA for priority review. The latest failure casts a darker shadow on the upcoming decision despite Orphazyme’s upbeat outlook.

In a statement, the Danish biotech announced that the drug did not meet its primary or secondary endpoints evaluating function and survival. But the company has not announced any data surrounding the failure, instead saying that it will publish the complete results later this year.

As­traZeneca caps PD-L1/CT­LA-4/chemo com­bo come­back with OS win. Is treme­li­mum­ab fi­nal­ly ready for ap­proval?

AstraZeneca’s closely-watched POSEIDON study continues to be the rare bright spot in its push for an in-house PD-L1/CTLA-4 combo.

Combining Imfinzi and tremelimumab with physicians’ choice of chemotherapy helped patients with stage IV non-small cell lung cancer live longer, the company reported — marking the first time the still-experimental tremelimumab has demonstrated an OS benefit.

For AstraZeneca and CEO Pascal Soriot, the positive readout — which is devoid of numbers — offers much-needed validation for the big bet they made on Imfinzi plus tremelimumab, after the PD-L1/CTLA-4 regimen failed multiple trials in head and neck cancer as well as lung cancer.

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Angela Merkel (AP Photo/Michael Sohn)

Covid-19 roundup: Pfiz­er sub­mits vac­cine for full ap­proval; Merkel op­pos­es Biden pro­pos­al to sus­pend IP for vac­cines

Pfizer and BioNTech said Friday that they’ve submitted a biologics license application to the FDA for full approval of their mRNA vaccine for those over the age of 16.

How long it will take the FDA to decide on the BLA will be set once it’s been formally accepted by the agency.

Peter Marks, director of the FDA’s Center for Biologics Evaluation and Research, previously told Endpoints News that the review of the BLA should take between three and four months, but it may be even faster than that.

Stéphane Bancel, Getty

Mod­er­na CEO brush­es off US sup­port for IP waiv­er, eyes more than $19B in Covid-19 vac­cine sales in 2021

Moderna is definitively more concerned with keeping pace with Pfizer in the race to vaccinate the world against Covid-19 than it is with Wednesday’s decision from the Biden administration to back an intellectual property waiver that aims to increase vaccine supplies worldwide.

In its first quarter earnings call on Thursday, Moderna CEO Stéphane Bancel shrugged off any suggestion that the newly US-backed intellectual property waiver would impact his company’s vaccine or bottom line. Still, the company’s stock price fell by about 9% in early morning trading.

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In­cyte ponies up $12M to set­tle char­i­ty foun­da­tion kick­back claims; US ex­er­cis­es op­tion for more dos­es of mon­key­pox vac­cine

One in a string of lawsuits targeting copay charity foundations, the DOJ has been hunting drugmaker Incyte for what prosecutors alleged was a kickback scheme to court patients. Now, Incyte is clearing its name.

Incyte will shell out $12.6 million to settle claims it funneled funds through a charity foundation to cover federal copays for patients taking its JAK inhibitor Jakafi, the DOJ said this week.

UP­DAT­ED: EMA safe­ty com­mit­tee seeks more in­fo on heart in­flam­ma­tion fol­low­ing Pfiz­er Covid-19 vac­cine

The European Medicines Agency’s safety committee said Friday that it’s aware of cases of inflammation of the heart muscle and inflammation of the membrane around the heart, mainly reported following vaccination with Pfizer’s Covid-19 vaccine, known in Europe as Comirnaty.

“There is no indication that these cases are due to the vaccine,” the EMA’s Pharmacovigilance Risk Assessment Committee said.

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Ron DePinho (file photo)

A 'fly­over' biotech launch­es in Texas with four Ron De­Pin­ho-found­ed com­pa­nies un­der its belt

In his 13 years at Genzyme, Michael Wyzga noticed something about East Coast drugmakers. Execs would often jet from Boston or New York to San Francisco to find more assets, and completely miss the work being done in flyover states, like Texas or Wisconsin.

“If it doesn’t come out of MGH or MIT or Harvard, probably not that interesting,” he said of the mindset.

Now, he and some well-known industry players are looking to change that, and they’ve reeled in just over $38 million to do it.

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