Two years af­ter in­vestor pan­ic, Avro­bio touts 100% re­sponse as they look to chart a path to­ward ap­proval

Two years af­ter Avro­bio’s ear­ly da­ta pan­icked in­vestors, the gene ther­a­py biotech thinks they have enough da­ta to be­gin plot­ting their bid for ac­cel­er­at­ed ap­proval — and launch a suite of pro­grams be­hind the lead drug that has dom­i­nat­ed the com­pa­ny to date.

Avro­bio an­nounced Mon­day that a year af­ter dos­ing, the first pa­tient giv­en the com­mer­cial form of their Fab­ry dis­ease gene ther­a­py saw 100% re­duc­tion in kid­ney sub­strate, the end­point the FDA us­es for ap­proval. The da­ta are just from one pa­tient but the re­sults add, CEO Ge­off MacK­ay said, to the grow­ing body of ev­i­dence that their gene ther­a­py can sig­nif­i­cant­ly and in­def­i­nite­ly curb the ge­net­ic dis­ease.

Ge­off MacK­ay

“Across the board — every sin­gle pa­tient, every time point, go­ing out as far as 3.5 years — we’re see­ing what we would hope to see,” MacK­ay told End­points News, adding of the most re­cent re­sult: “Cer­tain­ly, we couldn’t ask for more. The ef­fect was pro­found.”

To be sure, Avro­bio re­mains a ways away from fil­ing with the agency. But they have sub­mit­ted a pro­pos­al to the FDA to ex­pand their cur­rent 8 to 12-per­son study and make it piv­otal, point­ing them down a path that few gene ther­a­py com­pa­nies have yet gone down. And be­cause the biotech has spent years build­ing a closed-loop man­u­fac­tur­ing sys­tem for their ther­a­py, they think they’ll be able to avoid the CMC pit­falls that have snared ri­vals like blue­bird bio.

What the FDA says re­mains to be seen, but MacK­ay says they have al­ready got­ten ahead of oth­er com­pa­nies with their new plat­form, called Pla­to, with each step OK’d by the FDA.

“We’re con­fi­dent,” MacK­ay said. “Com­pa­nies have run in­to trou­ble when they haven’t done their char­ac­ter­i­za­tion ear­ly enough, they haven’t im­ple­ment­ed process changes ear­ly enough and they haven’t sort­ed out their po­ten­cy as­say ear­ly up.”

“And the whole rai­son d’être of Pla­to is that we want­ed to get our com­mer­cial stage plat­form in years ear­li­er,” he added. “And so all our process changes that are medi­um or large are ei­ther FDA ap­proved and in place and part of Pla­to.”

Like blue­bird, Avro­bio us­es ex-vi­vo gene ther­a­py, mean­ing they ex­tract cells from a pa­tient, ge­net­i­cal­ly mod­i­fy them and then im­plant them back in­to the pa­tient. While blue­bird has most no­tably used it for fix­ing in­her­it­ed blood dis­or­ders like sick­le cell ane­mia, Avro­bio goes af­ter lyso­so­mal dis­or­ders. These dis­or­ders arise when the en­zymes the body us­es as a waste sys­tem mal­func­tion; Avro­bio mod­i­fies the ex­tract­ed cells to se­crete a healthy en­zyme, which is then dis­trib­uted through­out the body.

Ear­ly da­ta showed ef­fi­ca­cy, al­low­ing one pa­tient to stop tak­ing the in­fu­sions of ar­ti­fi­cial en­zyme Fab­ry pa­tients re­ceive to keep their dis­ease (most­ly) un­der con­trol. But the re­sults al­so showed that vec­tor copy num­ber, a met­ric that tracks how much gene ther­a­py is stay­ing in the body, fell pre­cip­i­tous­ly.

MacK­ay ar­gued at the time that this was a nat­ur­al con­se­quence of ex-vi­vo gene ther­a­py, as most of the cells you im­plant don’t stick around and you’re left with a hand­ful of prog­en­i­tor cells that for years gen­er­ate en­zyme-se­cret­ing daugh­ter cells through­out the body. In­vestors didn’t be­lieve him much at the time, cut­ting their share price in half, and they still haven’t come back: Their stock is still a third of its Sep­tem­ber 2018 peak.

Still, the com­pa­ny has now shown that three out of five pa­tients from their Phase I are off en­zyme re­place­ment ther­a­py, with the first pa­tient now re­spond­ing for 3.5 years. And the com­mer­cial Pla­to plat­form is en­gi­neered to have a high­er vec­tor copy num­ber at the start, al­though MacK­ay is quick to in­sist the old­er form was still good.

“Why did we notch up Pla­to? Sim­ply be­cause we could,” he said. “It just gives us more con­fi­dence.”

Avro­bio al­so an­nounced ear­ly da­ta from their gene ther­a­py for Gauch­er dis­ease, an­oth­er lyso­so­mal dis­or­der, not­ing the first pa­tient saw around a 50% re­duc­tion on a key met­ric from where they were on en­zyme re­place­ment ther­a­py. In three of the pa­tients who re­ceived their ther­a­py for cysti­nosis, a rare dis­ease where crys­tals form that dam­age a pa­tient’s cells, they said they were see­ing vec­tor copy num­bers sim­i­lar to the Fab­ry tri­al. One pa­tient saw a two-grade im­prove­ment in his abil­i­ty to tol­er­ate light, one of the hall­marks of the dis­ease.

Now, with three pro­grams in the clin­ic and one — they hope — head­ing to­ward ap­proval, McK­ay is set­ting his sights on a longer line of ther­a­pies, in­clud­ing for Hunter’s dis­ease and Pompe dis­ease.

“We’ve en­tered the year as a Fab­ry com­pa­ny,” McK­ay said. “And we’d like to end the year with cer­tain­ly clar­i­ty on Fab­ry but al­so da­ta be­ing gen­er­at­ed from at least 5 of our 6 lyso­so­mal dis­or­der dis­ease tar­gets.”

Illustration: Assistant Editor Kathy Wong for Endpoints News

How Pur­due's $272M ad­dic­tion pay­out fund­ed a new home for its dis­card­ed non-opi­oid re­search

Don Kyle spent more than 20 years working for Purdue Pharma, right through the US opioid epidemic that led to the company’s rise and eventual infamy. But contrary to Purdue’s focus on OxyContin, Kyle was researching non-opioid painkillers — that is, until the company shelved his research.

As the company’s legal troubles mounted, Kyle found an unlikely way to reboot the project. In 2019, he took his work to an Oklahoma State University center that’s slated to receive more than two-thirds of the state’s $272 million settlement with Purdue over claims that the drugmaker’s behavior ignited the epidemic of opioid use and abuse.

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President Joe Biden at the State of the Union address with Vice President Kamala Harris and House Speaker Kevin McCarthy (Patrick Semansky/AP Images)

The drug pric­ing pres­i­dent: Biden warns of ve­to for any IRA re­peal at­tempts

President Joe Biden made clear in his “finish the job” State of the Union address last night that one of those jobs to be finished is insulin prices.

Biden’s push again to tackle insulin prices, after Republicans rebuffed the idea last summer and just after Biden won Medicare drug price negotiations/caps via the Inflation Reduction Act, shows how heavily he’s leaning into this work.

Rupert Vessey, Bristol Myers Squibb head of research and early development

Up­dat­ed: R&D tur­bu­lence at Bris­tol My­ers now in­cludes the end of a $650M al­liance and the de­par­ture of a top re­search cham­pi­on

This morning biotech Dragonfly put out word that Bristol Myers Squibb has handed back all rights to its IL-12 clinical-stage drug after spending $650 million to advance it into the clinic.

The news arrives amid a turbulent R&D stage for the pharma giant, which late last week highlighted Rupert Vessey’s decision to depart this summer as head of early-stage R&D following a crucial three-year stretch after he jumped to Bristol Myers in the big Celgene buyout. During that time he struck a series of deals for Bristol Myers, and also shepherded a number of Celgene programs down the pipeline, playing a major role for a lineup of biotechs which depended on him to champion their drugs.

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Bill Haney, Dragonfly CEO (Dave Pedley/Getty Images for SXSW)

Drag­on­fly chief: Bris­tol My­ers shouldn’t blame IL-12’s clin­i­cal per­for­mance for de­ci­sion to scrap the deal — eco­nom­ics played a key role

Bristol Myers Squibb says the IL-12 drug they were developing out of Dragonfly Therapeutics was scrubbed from the pipeline for a simple reason: It didn’t measure up on clinical performance.

But Bill Haney, the CEO of Dragonfly, is taking issue with that.

The early-stage drug, still in Phase I development, has passed muster with Bristol Myers’ general clinical expectations, advancing successfully while still in Phase I, he says.

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Utpal Koppikar, new Verily CFO

Ex­clu­sive: Ver­i­ly wel­comes Atara Bio­ther­a­peu­tics vet­er­an as new CFO

Verily, Alphabet’s life sciences outfit, has plucked a new CFO from the ranks of Atara Biotherapeutics, the company announced on Wednesday.

Utpal Koppikar joins Verily after a nearly five-year stint as CFO and senior VP at Atara, though his résumé also boasts roles at Gilead and Amgen.

The news follows a major reshuffling at Verily, including several senior departures earlier this year and a round of layoffs.

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Singer Nick Jonas is back at work for Dexcom, this time for its new G7 glucose monitor.

Dex­com's spokescelebri­ty Nick Jonas re­turns to Su­per Bowl in new glu­cose mon­i­tor com­mer­cial

Dexcom is going back to the Super Bowl with its pop singer and patient spokesperson Nick Jonas. Jonas takes center stage as the lone figure in the 30-second commercial showcasing Dexcom’s next-generation G7 continuous glucose monitoring (CGM) device.

Jonas’ sleight-of-hand tricks populate the commercial — he pinches his empty fingers together and pops them open to reveal the small CGM — even as he ends the ad, saying, “It’s not magic. It just feels that way.” Jonas then disappears in a puff of smoke.

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Richard Francis, newly-appointed Teva CEO (Novartis via Facebook)

New Te­va CEO Richard Fran­cis repri­or­i­tizes to 'get back to growth'

Six weeks into his new role at the helm of Teva Pharmaceutical, Richard Francis said it’s time to “get back to growth,” starting with a good look at the company’s priorities.

The chief executive has kicked off a strategic review, he announced during Teva’s quarterly call, which will continue over the next several months and produce results sometime in the middle of 2023. That means some pipeline cuts may be in store, he told Endpoints News, while declining to offer much more detail.

FDA Commissioner Robert Califf on Capitol Hill, Feb. 8, 2023 (Drew Angerer/Getty Images)

FDA com­mis­sion­er floats ideas on how to bet­ter han­dle the pan­dem­ic

FDA Commissioner Rob Califf joined the heads of the CDC and NIH in the hot seat today before a key House subcommittee, explaining that there needs to be a much faster, more coordinated way to oversee vaccine safety, and that foreign biopharma inspections, halted for years due to the pandemic, are slowly ramping up again.

Califf, who stressed to the House Energy and Commerce’s Subcommittee on Health that the CDC also needs better data, made clear that the FDA’s ability to monitor the safety of vaccines “would also benefit greatly by a coordinated federal public health data reporting authority.”

Sanofi is renewing its #VaccinesForDreams campaign with more stories, such as Juan's in Argentina (Sanofi)

Sanofi re­news so­cial cam­paign to re­mind that vac­cines let peo­ple ‘Dream Big’

Sanofi is highlighting people’s dreams — both big and small — to make the point that vaccines make them possible.

The renewed “Dream Big” global social media campaign’s newest dreamer is Juan, a teacher in the Misiones rainforest in Argentina whose story is told through videos on Instagram and Sanofi’s website with the hashtag #VaccinesForDreams.

The campaign ties to Sanofi’s broader umbrella initiative “Vaccine Stories” to promote the value of vaccines and drive awareness of the need for improved vaccination coverage.

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