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.”

Op­ti­miz­ing Cell and Gene Ther­a­py De­vel­op­ment and Pro­duc­tion: How Tech­nol­o­gy Providers Like Corn­ing Life Sci­ences are Spurring In­no­va­tion

Remarkable advances in cell and gene therapy over the last decade offer unprecedented therapeutic promise and bring new hope for many patients facing diseases once thought incurable. However, for cell and gene therapies to reach their full potential, researchers, manufacturers, life science companies, and academics will need to work together to solve the significant challenges facing the industry.

Amid mon­key­pox fears, biotechs spring to ac­tion; Mod­er­na’s CFO trou­ble; Cuts, cuts every­where; Craft­ing the right pro­teins; 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.

It’s always a bittersweet moment saying goodbye, but as Josh Sullivan goes off to new adventures we are grateful for the way he’s built up the Endpoints Manufacturing section — which the rest of the team will now carry forward. If you’re not already, this may be a good time to sign up for your weekly dose of drug manufacturing news. Thank you for reading and wish you a restful weekend.

Bay­er sounds re­treat from a $670 mil­lion CAR-T pact in the wake of a pa­tient death

Two months after Atara Biotherapeutics hit the hold button on its lead CAR-T 2.0 therapy following a patient death, putting the company under the watchful eye of the FDA, its Big Pharma partners at Bayer are bowing out of a $670 million global alliance. And the move is forcing a revamp of Atara’s pipeline plans, even as research execs vow to continue work on the two drugs allied with Bayer 18 months ago, which delivered a $60 million cash upfront.

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Try­ing to shake up the Parkin­son's par­a­digm, Ab­b­Vie sub­mits NDA for con­tin­u­ous, 24-hour in­fu­sion ther­a­py

AbbVie is approaching the FDA with a new therapy to potentially treat Parkinson’s disease, using prodrugs of two medications commonly used for the condition.

The Big Pharma submitted its NDA for ABBV-951, a solution of levodopa and carbidopa prodrugs being evaluated in advanced Parkinson’s patients who don’t respond well to oral therapy, AbbVie announced Friday morning. Researchers are hoping a positive Phase III study that reads out in late October will help move things along quickly at the agency.

Sanofi and Re­gen­eron clear the fin­ish line in an in­flam­ma­to­ry esoph­a­gus dis­ease, leav­ing Take­da in the dust

With atopic dermatitis rivals breathing down Dupixent’s neck, Sanofi and Regeneron on Friday secured a first win in new territory in what Sanofi’s head of immunology and inflammation Naimish Patel called the fastest approval he’s ever seen.

The FDA approved Dupixent on Friday to treat patients 12 years and older with eosinophilic esophagitis (EoE), an inflammatory condition that causes swelling and scarring of the esophagus. The approval came just a couple months after regulators granted Dupixent priority review, and months ahead of its PDUFA date on Aug. 3.

Fu­ji­film con­tin­ues its biotech build­ing spree with new fa­cil­i­ty in Chi­na

A Japanese conglomerate is making a big play in China with the opening of a new facility, as it continues to expand.

Fujifilm Irvine Scientific has opened its new Innovation and Collaboration Center in Suzhou New District, China, an area in Jiangsu province specifically designated for technological and industrial development.

According to Fujifilm, the 12,000-square-foot site will be responsible for the company’s cell culture media optimization, analysis and design services. Cell culture media itself often requires customization of formulas and protocols to achieve the desired quantity and quality of therapeutic desired. Fujifilm Irvine Scientific is offering these services from its headquarters in California and Japan to its customers globally, as well as in China now.

Emer Cooke, EMA director (AP Photo/Geert Vanden Wijngaert)

Ahead of FDA, EMA rec­om­mends au­tho­riz­ing new gene ther­a­py treat­ment for ul­tra-rare dis­ease

Aromatic amino acid decarboxylase (AADC) deficiency is an ultra-rare genetic disease that leaves patients unable to produce certain hormones in the brain, such as dopamine and serotonin, usually leading to developmental delays, weak muscle tone and inability to control the movement of the limbs. It can also lead to multiple organ failure.

To date, there have been no treatments approved for AADC deficiency, which has been identified in less than 150 patients.

Ather­sys tries to post-hoc-an­a­lyze its way out of an­oth­er tri­al fail for stroke stem cell ther­a­py

Athersys’ stem cell therapy has failed yet again.

In a 206-person trial conducted in Japan, Athersys’ stem cell therapy for stroke failed its primary endpoint of “excellent outcome,” a combined measure of three stroke recovery scores.

While a greater percentage of patients in the treatment group reached the primary endpoint compared to placebo, that difference was not statistically significant.

Siddhartha Mukherjee (Brian Ach/Getty Images for The New Yorker)

All Blue's $733M bid to ac­quire Zymeworks turns hos­tile as board bat­tles back — af­ter a biotech celebri­ty jumps in

Yesterday, the team at All Blue Capital — bent on the takeover of a badly battered Zymeworks — brought in celebrated oncologist, Pulitzer prize-winning writer and biotech exec Siddhartha Mukherjee to add some glitz to their proposed board. But they’re still not winning over any converts.

This morning, Zymeworks’ board officially turned this acquisition offer into a hostile showdown, rejecting the unsolicited offer and marshaling its forces to prevent a buyout at $10.50 per share.

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