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.

Grow­ing ac­cep­tance of ac­cel­er­at­ed path­ways for nov­el treat­ments: but does reg­u­la­to­ry ap­proval lead to com­mer­cial suc­cess?

By Mwango Kashoki, MD, MPH, Vice President-Technical, and Richard Macaulay, Senior Director, of Parexel Regulatory & Access

In recent years, we’ve seen a significant uptake in the use of regulatory options by companies looking to accelerate the journey of life-saving drugs to market. In 2018, 73% of the novel drugs approved by the U.S. Federal Drug Administration (FDA) were designated under one or more expedited development program categories (Fast Track, Breakthrough Therapy, Priority Review, and Accelerated Approval).ᶦ

Sanofi out­lines big API plans as coro­n­avirus out­break re­port­ed­ly threat­ens short­age of 150 drugs

As the world becomes increasingly dependant on Asia for the ingredients of its medicines, Sanofi sees business to be done in Europe.

The French drugmaker said it’s creating the world’s second largest active pharmaceutical ingredients (API) manufacturer by spinning out its six current sites into a standalone company: Brindisi (Italy), Frankfurt Chemistry (Germany), Haverhill (UK), St Aubin les Elbeuf (France), Újpest (Hungary) and Vertolaye (France). They have mapped out €1 billion in expected sales by 2022 and 3,100 employees for the new operations headquartered in France.

UP­DAT­ED: NGM Bio takes leap for­ward in crowd­ed NASH field

South San Francisco-based NGM Bio may have underwhelmed with its interim analysis of a key cohort from a mid-stage NASH study last fall — but stellar topline data unveiled on Monday showed the compound induced significant signs of antifibrotic activity, NASH resolution and liver fat reduction, sending the company’s stock soaring.

There are an estimated 50+ companies focused on developing drugs for non-alcoholic steatohepatitis, or NASH, a common liver disease that has long flummoxed researchers. The first wave of NASH drug developers struggled with efficacy as well as safety — and companies big and small have crashed and burned.

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Mickey Kertesz, KidsandArtOrg via YouTube

Soft­Bank's newest, $165M biotech in­vest­ment looks for in­fec­tious traces in the blood

SoftBank has found its newest biotech investment.

The Japanese bank has invested $165 million into Karius, a company that uses blood tests to diagnose infectious diseases, as part of its new Vision Fund 2. The full scope of the new fund has yet to be announced, but the first and newly-beleaguered Vision Fund poured $100 billion into technology companies, including the biotechs Vir Biotechnology and Roivant and the sequencing company 10x Genomics.

Methicillin-resistant Staph aureus (Shutterstock)

FDA grants ‘break­through’ sta­tus to an­tibi­ot­ic al­ter­na­tive as Con­tra­Fect rush­es to join fight against su­per­bug

An experimental drug that promises to be the first anti-infective agent to prove superior to vancomycin — an antibiotic approved in 1958 — has notched the FDA’s “breakthrough” status.

ContraFect said the designation was based on Phase II data in which exebacase was tested against a superbug known as methicillin-resistant Staph aureus, or MRSA. In a subgroup analysis, the clinical responder rate at day 14 was 42.8% higher than that among those treated with standard of care, the company said (p=0.010).

Zhong Nanshan, CGTN via YouTube

Har­vard joins coro­n­avirus fight with $115 mil­lion and a high-pro­file Chi­nese part­ner

For two months, as the novel coronavirus swelled from a few early cases tied to a Wuhan market to a global epidemic, most of the world’s focus and dollars have flowed toward emergency initiatives: building vaccines at a record pace, plucking experimental antivirals out of freezers to see what sticks and immunizing mice for new antibodies.

Now a new and well-funded collaboration between Harvard and a top Chinese research institute will play the long game. In a 5-year, $115 million initiative backed by China Evergrande Group, researchers from the Harvard Medical School, Harvard T.H. Chan School of Public Health and Guangzhou Institute for Respiratory Health will study the virus in an effort to develop therapies against infections by the novel coronavirus, known as SARS–CoV-2, and to prevent new ones.

No­var­tis gets a boost in block­buster mul­ti­ple scle­ro­sis race with Roche

In the first step of what’s likely to be a long and uphill battle for the drugmaker, the FDA has accepted Novartis’s BLA submission for a new multiple sclerosis drug and given it priority review. The PDUFA date for the potential blockbuster drug is in June.

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Juergen Horn

An­i­mal health vet Juer­gen Horn makes new an­ti­body play for pets, rak­ing $15M in Se­ries A haul

Zoetis forked over $85 million in 2017 to acquire Nexvet Biopharma and its pipeline of monoclonal antibodies. Juergen Horn, Nexvet’s former chief product development officer, has now secured $15 million for his own biologic company for animals: Invetx.

Buoyed by emerging advances in gene therapies for humans, scientists have started looking at harnessing the technology for animals setting up companies such as Penn-partnered Scout Bio and George Church-founded Rejuvenate Bio. But akin to Nexvet, Invetx is working on leveraging the time-tested science of monoclonal antibodies to treat chronic diseases that afflict man’s best friend.

As coro­n­avirus out­break reach­es 'tip­ping point,' GSK lends ad­ju­vant tech to Chi­nese part­ner armed with pre­clin­i­cal vac­cine

As the coronavirus originating out of Wuhan spreads to South Korea, Italy and Iran, stoking already intense fears of a pandemic, GlaxoSmithKline has found another pair of trusted hands to place its adjuvant system. China’s Clover Biopharmaceuticals will add the adjuvant to its preclinical, protein-based vaccine candidate against SARS-CoV-2.

Clover, which is based in the inland city of Chengdu, boasts of a platform dubbed Trimer-Tag that produces covalently-trimerized fusion proteins. Its candidate, COVID-19 S-Trimer, resembles the viral spike (S)-protein found in the virus.