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.

MedTech clinical trials require a unique regulatory and study design approach and so engaging a highly experienced CRO to ensure compliance and accurate data across all stages is critical to development milestones.

In­no­v­a­tive MedTech De­mands Spe­cial­ist Clin­i­cal Tri­al Reg­u­la­to­ry Af­fairs and De­sign

Avance Clinical is the Australian CRO for international biotechs providing world-class clinical research services with FDA-accepted data across all phases. With Avance Clinical, biotech companies can leverage Australia’s supportive clinical trials environment which includes no IND requirement plus a 43.5% Government incentive rebate on clinical spend. The CRO has been delivering clinical drug development services for international biotechs for FDA and EMA regulatory approval for the past 24 years. The company has been recognized for the past two consecutive years with the prestigious Frost & Sullivan CRO Best Practices Award and a finalist in Informa Pharma’s Best CRO award for 2022.

His­toric drug pric­ing re­forms pass; Pfiz­er ac­quires GBT; The long search for non-opi­oid pain drugs; and more

Welcome back to Endpoints Weekly, your review of the week’s top biopharma headlines. Want this in your inbox every Saturday morning? Current Endpoints readers can visit their reader profile to add Endpoints Weekly. New to Endpoints? Sign up here.

The Endpoints Weekly has officially crossed the 60,000 mark on subscribers — thanks to all of your support. As the editorial team grows, we’ve been able to do a lot more, with many of those on display this week. Be sure to check out Lei Lei Wu’s deep dive on pain R&D. If you missed it, you may also rewatch her companion panel here.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 147,700+ biopharma pros reading Endpoints daily — and it's free.

Gold for adults, sil­ver for in­fants: Pfiz­er's Pre­vnar 2.0 head­ed to FDA months af­ter Mer­ck­'s green light

Pfizer was first to the finish line for the next-gen pneumococcal vaccine in adults, but Merck beat its rival with a jab for children in June.

Now, two months after Merck’s 15-valent Vaxneuvance won the FDA stamp of approval for kids, Pfizer is out with some late-stage data on its 20-valent shot for infants.

Known as Prevnar 20 for adults, Pfizer’s 20vPnC will head to the FDA by the end of this year for an approval request in infants, the Big Pharma said Friday morning. Discussions with the FDA will occur first and more late-stage pediatric trials are expected to read out soon, informing the regulatory pathway in other countries and regions.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 147,700+ biopharma pros reading Endpoints daily — and it's free.

No­var­tis re­ports two pa­tient deaths af­ter treat­ment with Zol­gens­ma

Two children with spinal muscular atrophy have died after receiving Novartis’ Zolgensma, a gene therapy designed as a one-time treatment for the rare fatal disease.

The deaths, which resulted from acute liver failure, occurred in Russia and Kazakhstan, Novartis confirmed in a statement to Endpoints News. Having notified health authorities across all the markets where Zolgensma is available, it will update the drug label “to specify that fatal acute liver failure has been reported,” a spokesperson wrote.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 147,700+ biopharma pros reading Endpoints daily — and it's free.

Benjamin Oakes, Scribe Therapeutics CEO

CEO of Doud­na spin­out: With­in five years, genome ed­i­tors will have a 're­al­ly big im­pact' on pa­tients' lives

“CRISPR-by-design” is the idea behind Scribe Therapeutics, a company spun out from Jennifer Doudna’s Nobel-winning lab that’s competing in a closely-tracked field of genome editor companies just starting to make their way to the clinic.

After nabbing $100 million last March for its Series B funding round, Scribe is taking a different tack from some of its competitors, crafting a new enzyme isolated from bacteria called CasX, which has now been tweaked extensively and may be targeted to a range of genome-related diseases, offering a plethora of therapeutic options.

Endpoints Premium

Premium subscription required

Unlock this article along with other benefits by subscribing to one of our paid plans.

House pass­es his­toric drug pric­ing re­forms, lin­ing up decades-in-the-mak­ing win for Biden and De­moc­rats

The US House of Representatives today voted along party lines (all Dems voted for it), 220-207 to pass new, wide-ranging legislation that will allow Medicare drug price negotiations for the first time ever, and cap seniors’ drug expenses to $2,000 per year and seniors’ insulin costs at $35 per month.

Setting up a major victory for President Joe Biden, representatives returned from their summer recess to pass the Inflation Reduction Act, even as many noted the bill would only modestly reduce inflation.

Senate Finance Committee Chair Ron Wyden (D-OR) (Francis Chung/E&E News/POLITICO via AP Images)

Sen­ate Fi­nance chair con­tin­ues his in­ves­ti­ga­tion in­to phar­ma tax­es with re­quests for Am­gen

Amgen is the latest pharma company to appear on the radar of Senate Finance Committee Chair Ron Wyden (D-OR), who is investigating the way pharma companies are using subsidiaries in low- or zero-tax countries to lower their tax bills.

Like its peers Merck, AbbVie and Bristol Myers Squibb, Wyden notes how Amgen uses its Puerto Rico operations to consistently pay tax rates that are substantially lower than the U.S. corporate tax rate of 21%, with an effective tax rate of 10.7% in 2020 and 12.1% in 2021.

FDA ap­proves sec­ond in­di­ca­tion for As­traZeneca and Dai­ichi's En­her­tu in less than a week

AstraZeneca and Daiichi Sankyo’s antibody-drug conjugate Enhertu scored its second approval in less than a week, this time for a subset of lung cancer patients.

Enhertu received accelerated approval on Thursday to treat adults with unresectable or metastatic non-small cell lung cancer (NSCLC) whose tumors have activating HER2 (ERBB2) mutations, and who have already received a prior systemic therapy.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 147,700+ biopharma pros reading Endpoints daily — and it's free.

J&J to re­move talc prod­ucts from shelves world­wide, re­plac­ing with corn­starch-based port­fo­lio

After controversially spinning out its talc liabilities and filing for bankruptcy in an attempt to settle 38,000 lawsuits, Johnson & Johnson is now changing up the formula for its baby powder products.

J&J is beginning the transition to an all cornstarch-based baby powder portfolio, the pharma giant announced on Thursday — just months after a federal judge ruled in favor of its “Texas two-step” bankruptcy to settle allegations that its talc products contained asbestos and caused cancer. An appeals court has since agreed to revisit that case.