En­cour­ag­ing gene ther­a­py da­ta give uniQure an in­jec­tion of con­fi­dence as it preps PhI­II show­down with Spark

Gene ther­a­py com­pa­ny uniQure start­ed the week in style with the news that it’s dosed the first pa­tient in its Phase III tri­al — a cru­cial step to­ward its quest for the best-in-class, first-in-mar­ket ti­tle in he­mo­phil­ia B gene ther­a­py. And to­day it’s of­fer­ing an up­date on the kind of mid-stage da­ta it’s armed with.

Matt Ka­pus­ta

Mean Fac­tor IX lev­els hit 38% of nor­mal lev­els 12 weeks af­ter the three pa­tients tracked in the Phase IIb study re­ceived the one-time in­jec­tion, reach­ing what the com­pa­ny calls “the nor­mal range” and well above the 12% com­mon­ly re­gard­ed as suf­fi­cient to sub­stan­tial­ly re­duce spon­ta­neous bleeds.

It’s the first look at da­ta three months post-ad­min­is­tra­tion — sig­nif­i­cant be­cause most pa­tients don’t be­gin to start plateau­ing un­til that point, CEO Matt Ka­pus­ta tells me in a pre­view of the re­sults, which fol­lows an up­beat snap­shot in No­vem­ber on six-week da­ta.

So have they reached the peak in FIX lev­els? Prob­a­bly not, Ka­pus­ta said.

The best way to glean that is we ac­tu­al­ly did a Phase I/II study with the first gen­er­a­tion prod­uct that is near­ly iden­ti­cal to the AMT-061 and in­clud­ed pa­tients that were at the same dose. […] Of the 9 pa­tients that were off of pro­phy­lax­is, 8 of them had Fac­tor IX ac­tiv­i­ty that was high­er at 52 weeks or — their lat­est mea­sure­ment was high­er than what it was at 12 weeks. […] So we don’t know if that will con­tin­ue to be the case, but that’s prob­a­bly — look­ing at those ki­net­ics from the Phase I/II study sug­gests that there is po­ten­tial for mean­ing­ful in­creas­es go­ing for­ward.

Since the pa­tients be­gan dos­ing at dif­fer­ent times, uniQure al­so gleaned in­sights in­to the (slight­ly) longer term FIX ac­tiv­i­ties: 48% for the first pa­tient at week 16; 25% for the sec­ond pa­tient at week 14; and 51% for the third pa­tient at 12 weeks.

“It’s not un­usu­al to have a three, maybe four-fold mul­ti­ple be­tween your min­i­mum and your max­i­mum,” Ka­pus­ta says. “Here of course we’ve got about a two-fold. So in our view the vari­abil­i­ty is ac­tu­al­ly tighter.”

The new round of da­ta drew uni­ver­sal ap­plause from an­a­lysts, with Chardan spec­u­lat­ing that the com­pa­ny is now a prime takeover tar­get. Shares are up 4%.

A chief ri­val of Spark Ther­a­peu­tics — which is tap­ping in­to he­mo­phil­ia as a fol­low-up to its ground­break­ing gene ther­a­py for the eye — Lex­ing­ton, MA- and Am­s­ter­dam-based uniQure $QURE pleased in­vestors and an­a­lysts back in No­vem­ber when it re­port­ed mean FIX lev­els of 31% at six weeks.

While care­ful to note that “we don’t love com­ment­ing on oth­er peo­ple’s da­ta,” Ka­pus­ta cit­ed the high lev­els of FIX ac­tiv­i­ty, low im­muno­genic­i­ty — none of uniQure’s pa­tients have re­quired im­muno­sup­pres­sion so far — and the fact that it doesn’t ex­clude pa­tients with pre-ex­ist­ing an­ti­bod­ies to AAV vec­tors as rea­sons to be­lieve that they have a “high­ly com­pa­ra­ble if not po­ten­tial­ly an op­ti­mized or su­pe­ri­or tar­get prod­uct pro­file.”

But the re­al show­down will take place in the piv­otal stage, as uniQure catch­es up with a Phase III pro­gram that Spark part­ner Pfiz­er be­gan last sum­mer.

With 20 ac­tive sites across the US and Eu­rope, uniQure’s Phase III is ex­pect­ed to en­roll 50 pa­tients by the end of the year. Top-line da­ta on the pri­ma­ry end­point — FIX ac­tiv­i­ty af­ter six months — should be ready in late 2020, paving the way for a BLA sub­mis­sion in 2021, Ka­pus­ta said.

Regeneron CEO Leonard Schleifer speaks at a meeting with President Donald Trump, members of the Coronavirus Task Force, and pharmaceutical executives in the Cabinet Room of the White House (AP Photo/Andrew Harnik)

OWS shifts spot­light to drugs to fight Covid-19, hand­ing Re­gen­eron $450M to be­gin large scale man­u­fac­tur­ing in the US

The US government is on a spending spree. And after committing billions to vaccines defense operations are now doling out more of the big bucks through Operation Warp Speed to back a rapid flip of a drug into the market to stop Covid-19 from ravaging patients — possibly inside of 2 months.

The beneficiary this morning is Regeneron, the big biotech engaged in a frenzied race to develop an antibody cocktail called REGN-COV2 that just started a late-stage program to prove its worth in fighting the virus. BARDA and the Department of Defense are awarding Regeneron a $450 million contract to cover bulk delivery of the cocktail starting as early as late summer, with money added for fill/finish and storage activities.

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UP­DAT­ED: Bio­gen shares spike as ex­ecs com­plete a de­layed pitch for their con­tro­ver­sial Alzheimer's drug — the next move be­longs to the FDA

Biogen is stepping out onto the high wire today, reporting that the team working on the controversial Alzheimer’s drug aducanumab has now completed their submission to the FDA. And they want the agency to bless it with a priority review that would cut the agency’s decision-making time to a mere 6 months.

The news drove a 10% spike in Biogen’s stock $BIIB ahead of the bell.

Part of that spike can be attributed to a relief rally. Biogen execs rattled backers and a host of analysts earlier in the year when they unexpectedly delayed their filing to the third quarter. That delay provoked all manner of speculation after CEO Michel Vounatsos and R&D chief Al Sandrock failed to persuade influential observers that the pandemic and other factors had slowed the timeline for filing. Actually making the pitch at least satisfies skeptics that the FDA was not likely pushing back as Biogen was pushing in. From the start, Biogen execs claimed that they were doing everything in cooperation with the FDA, saying that regulators had signaled their interest in reviewing the submission.

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Daniel O'Day, Gilead CEO (Kevin Dietsch/UPI/Bloomberg via Getty Images)

A new study points to $6.5B in pub­lic sup­port build­ing the sci­en­tif­ic foun­da­tion of Gilead­'s remde­sivir. Should that be re­flect­ed in the price?

By drug R&D standards, Gilead’s move to repurpose remdesivir for Covid-19 and grab an emergency use authorization was a remarkably easy, low-cost layup that required modest efficacy and a clean safety profile from just a small group of patients.

The drug OK also arrived after Gilead had paid much of the freight on getting it positioned to move fast.

In a study by Fred Ledley, director of the Center for Integration of Science and Industry at Bentley University in Waltham, MA, researchers concluded that the NIH had invested only $46.5 million in the research devoted to the drug ahead of the pandemic, a small sum compared to the more than $1 billion Gilead expected to spend getting it out this year, all on top of what it had already cost in R&D expenses.

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Noubar Afeyan, Flagship CEO and Tessera chairman (Victor Boyko/Getty Images)

Flag­ship ex­ecs take a les­son from na­ture to mas­ter ‘gene writ­ing,’ launch­ing a star-stud­ded biotech with big am­bi­tions to cure dis­ease

Flagship Pioneering has opened up its deep pockets to fund a biotech upstart out to revolutionize the whole gene therapy/gene editing field — before gene editing has even made it to the market. And they’ve surrounded themselves with some marquee scientists and execs who have crowded around to help shepherd the technology ahead.

The lead player here is Flagship general partner Geoff von Maltzahn, an MIT-trained synthetic biologist who set out in 2018 to do CRISPR — a widely used gene editing tool — and other rival technologies one or two better. Von Maltzahn has been working with Sana co-founder Jake Rubens, another synthetic biology player out of MIT who he describes as his “superstar,” who’s taken the CSO role.

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FDA bars the door — for now — against Mer­ck’s star can­cer drug af­ter Roche beat them to the punch

Merck has been handed a rare setback at the FDA.

After filing for the accelerated approval of a combination of their star PD-1 drug Keytruda with Eisai’s Lenvima as a first-line treatment for unresectable hepatocellular carcinoma, the FDA nixed the move, handing out a CRL because Roche beat them to the punch on the same indication by a matter of weeks.

According to Merck:

Ahead of the Prescription Drug User Fee Act action dates of Merck’s and Eisai’s applications, another combination therapy was approved based on a randomized, controlled trial that demonstrated overall survival. Consequently, the CRL stated that Merck’s and Eisai’s applications do not provide evidence that Keytruda in combination with Lenvima represents a meaningful advantage over available therapies for the treatment of unresectable or metastatic HCC with no prior systemic therapy for advanced disease. Since the applications for KEYNOTE-524/Study 116 no longer meet the criteria for accelerated approval, both companies plan to work with the FDA to take appropriate next steps, which include conducting a well-controlled clinical trial that demonstrates substantial evidence of effectiveness and the clinical benefit of the combination.

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Covid-19 roundup: Mod­er­na sticks to Ju­ly for its Phase III as ru­mors swirl; Fol­low­ing US lead, EU buys up Covid-19 treat­ments

The Phase III might be delayed from its original early July goal, but Moderna says it will still kick off the pivotal study for what could ultimately be the first Covid-19 vaccine before the end of the month.

A day after Reuters reported that squabbling between the Cambridge biotech and government regulators had held up the trial by about two weeks, Moderna released a statement saying that they had completed enrollment of their 650-person Phase II trial and were on track to begin Phase III by the end of the month. The protocol for that study, which is meant to prove whether or not the vaccine can prevent people from becoming sick, has been finalized, they said.

Adrian Gottschalk, Foghorn CEO

Mer­ck dan­gles up to $425 mil­lion to team with Flag­ship’s Foghorn Ther­a­peu­tics on drug­ging the shape of DNA

Two years after it first emerged from stealth mode, Flagship’s Foghorn Therapeutics has nabbed its first Big Pharma partner as Merck signs on to the biotech’s vision of drugging the very shape of DNA.

The deal, worth up to $425 million but with the upfront cash undisclosed, comes as Foghorn nears a pivot to a clinical stage biotech. The Cambridge-based company has added nearly 60 staffers from the 25 it had when it first emerged out of Flagship and, CEO Adrian Gottschalk said, they have finally refined the screening technology at the heart of the company, with plans to file their first IND towards the end of the year.

John Reed, Sanofi R&D chief (Endpoints News)

John Reed brings NK cells in­to Sanofi's CD38 ri­val­ry with J&J — and of­fers thumbs up for Kiadis' new fo­cus

Sanofi doesn’t just want to be a challenger to J&J’s dominant Darzalex multiple myeloma franchise. It’s looking to pioneer a new approach by pairing its own — newly approved — anti-CD38 drug with an NK cell therapy it’s just picked up.

The French pharma giant has teed up $19.7 million (€17.5 million) upfront and close to a billion dollars (€857.5 million) in milestones for a license to Kiadis Pharma’s preclinical K-NK004 program, which consists of NK cells that have been genetically engineered not to express CD38.

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GSK sets the stage for a toe-to-toe mar­ket show­down with Gilead­'s HIV cham­pi­on Tru­va­da

ViiV Healthcare and majority owner GlaxoSmithKline have cleared another important hurdle on a long-running quest to challenge Gilead’s dominance in preventative HIV treatments.

The final analysis of a new study shows the GSK subsidiary’s long-lasting injection, cabotegravir, proved 66% more effective in HIV prevention than Gilead’s breakthrough Truvada pill. And they now intend to carve away some of the blockbuster revenue that Gilead has enjoyed for years.