Avro­bio re­tools Fab­ry gene ther­a­py plans af­ter com­pet­ing drug's full ap­proval shuts path­way to an ac­cel­er­at­ed nod

It’s been a long road for lentivi­ral gene ther­a­py play­er Avro­bio in the rare lyso­so­mal dis­or­der Fab­ry dis­ease af­ter ear­ly da­ta sent in­vestors run­ning for the hills back in 2018. Right on the heels of a promis­ing read­out, Avro­bio will now tin­ker with its reg­u­la­to­ry plans for that ther­a­py af­ter the FDA flipped the script and hand­ed a com­pet­ing drug an un­like­ly full ap­proval.

The biotech will re­jig­ger its de­vel­op­ment plans for AVR-RD-01, an in­ves­ti­ga­tion­al gene ther­a­py for Fab­ry dis­ease, af­ter the FDA grant­ed a full ap­proval to Sanofi’s en­zyme re­place­ment ther­a­py Fab­razyme back in March, val­i­dat­ing a new kid­ney biop­sy sur­ro­gate end­point Avro­bio now hopes to pur­sue, the com­pa­ny said Mon­day.

Avro­bio was in talks with the FDA to pur­sue an ac­cel­er­at­ed ap­proval for AVR-RD-01 based on kid­ney sub­strate re­duc­tion with a con­fir­ma­to­ry study to fol­low. Af­ter it sub­mit­ted its brief­ing book to the FDA, the agency hand­ed Fab­razyme a full ap­proval — 18 years af­ter it first re­ceived an ac­cel­er­at­ed nod based on the re­duc­tion of the lipid Gb3.

That ap­proval marked a new path for­ward for ERTs, which are used as the stan­dard of care in Fab­ry dis­ease, to re­ceive full nods, but forced Avro­bio to fo­cus on a head-to-head reg­is­tra­tional study against Fab­razyme, and shut off its hopes for an ac­cel­er­at­ed OK. Avro­bio will still go ahead on ex­pand­ing its Phase II study, which has dosed six pa­tients so far and has seen im­prove­ment on end­points “sim­i­lar” to Gb3 re­duc­tion, with hopes of con­vinc­ing the FDA to move ahead on a Phase III reg­is­tra­tional study pegged for the mid­dle of next year.

But noth­ing’s cer­tain for Avro­bio, and it warned that one ther­a­py’s ac­cept­ed sur­ro­gate end­point doesn’t nec­es­sar­i­ly trans­late to an­oth­er. The ex vi­vo ther­a­py us­es pa­tient’s en­gi­neered hematopoi­et­ic stem cells to re­place pa­tients’ func­tion­al en­zymes used to break down Gb3.

Ge­off MacK­ay

Start­ing this quar­ter, Avro­bio in­tends to ex­pand en­roll­ment in its Phase II FAB-GT study to in­clude fe­male par­tic­i­pants and pa­tients re­gard­less of an­ti­body-sta­tus ex­clu­sions with the goal of hit­ting 14 pa­tients to­tal. Mean­while, in­ves­ti­ga­tors will al­so mon­i­tor a new set of bio­mark­er end­points in­tend­ed to high­light ERTs’ short­com­ings, in­clud­ing po­ten­tial for AVR-RD-01 “to ad­dress car­dio­vas­cu­lar and cen­tral ner­vous sys­tem man­i­fes­ta­tions,” the com­pa­ny said.

It’s an un­wel­come turn of events for Avro­bio af­ter it re­vealed tri­umphant Phase II fol­low-up da­ta in Feb­ru­ary show­ing a 100% re­duc­tion in kid­ney sub­strate lev­els af­ter one year in a sin­gle pa­tient dosed with the com­mer­cial form of AVR-RD-01. It was a small but promis­ing win­dow in­to the pos­si­bil­i­ty of a rel­a­tive­ly quick path to mar­ket, which could now be pushed back con­sid­er­ably.

Ear­ly da­ta for AVR-RD-01 left a bad taste in in­vestors’ mouths af­ter the ther­a­py showed ef­fi­ca­cy in Fab­ry in late 2018 but al­so post­ed low vec­tor copy num­bers, an in­di­ca­tor of how long the ther­a­py hangs around in the body. CEO Ge­off MacK­ay at the time ar­gued those da­ta were in line with ex­pec­ta­tions for how the ex vi­vo ther­a­py was de­signed to work, but in­vestors fled in droves all the same. Mean­while, the com­pa­ny tout­ed da­ta show­ing three of five pa­tients in a Phase I test had moved off ERTs for their dis­ease.

Ed­i­tor’s Note: This sto­ry has been up­dat­ed to clar­i­fy the pri­ma­ry end­point in Avro­bio’s Phase II study for AVR-RD-01.

Mov­ing Out of the Clin­ic with Dig­i­tal Tools: Mo­bile Spirom­e­try Dur­ing COVID-19 & Be­yond

An important technology in assessing lung function, spirometry offers crucial data for the diagnosis and monitoring of pulmonary system diseases, as well as the ongoing measurement of treatment efficacy. But trends in the healthcare industry and new challenges introduced by the COVID-19 pandemic are causing professionals in clinical practice and research to reevaluate spirometry’s deployment methods and best practices.

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Sanofi, Glax­o­SmithK­line jump back in­to the PhI­II race for a Covid vac­cine — as the win­ners con­gre­gate be­hind the fin­ish line

Sanofi got out early in the race to develop a vaccine using more of a traditional approach, then derailed late last year as their candidate failed to work in older people. Now, after likely missing the bus for the bulk of the world’s affluent nations, they’re back from that embarrassing collapse with a second attempt using GSK’s adjuvant that may get them back on track — with a potential Q4 launch that the rest of the world will be paying close attention to.

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SCO­TUS de­clines to re­view En­brel biosim­i­lar case, tee­ing up 30+ years of ex­clu­siv­i­ty and $20B more for Am­gen’s block­buster

As the House Oversight Committee is set to grill AbbVie CEO Richard Gonzalez on Tuesday over tactics to block competition for its best-selling drug of all time, another decision on Capitol Hill on Monday opened the door for billions more in Amgen profits over the next eight years.

The Supreme Court on Monday denied Novartis subsidiary Sandoz’s petition to review a Federal Circuit’s July 2020 decision concerning its biosimilar Erelzi (etanercept-szzs), which FDA approved in 2016 as a biosimilar to Amgen’s Enbrel (etanercept). Samsung’s Enbrel biosimilar Eticovo also won approval in 2019 and remains sidelined.

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How to man­u­fac­ture Covid-19 vac­cines with­out the help of J&J, Pfiz­er or Mod­er­na? Bi­ol­yse sees the dif­fi­cul­ties up close

When Biolyse, an Ontario-based manufacturer of sterile injectables, forged a deal with Bolivia last week to manufacture up to 50 million J&J Covid-19 vaccine doses, the agreement kicked off what will prove to be a test case for how difficult the system of compulsory licenses is to navigate.

The first problem: When Biolyse asked J&J, via a March letter, to license its Covid-19 vaccine, manufacture it in Canada and pay 5% royalties on shipments to needy, low-income countries, J&J rejected the offer, refusing to negotiate. J&J also did not respond to a request for comment.

Tim Mayleben (L) and Sheldon Koenig (Esperion)

On the heels of a sting­ing Q1 set­back, Es­pe­ri­on's long­time cham­pi­on is ex­it­ing the helm and turn­ing the wheel over to a mar­ket­ing pro

Just days after getting stung by criticism from a badly disappointed group of analysts, there’s a big change happening today at the helm of Esperion $ESPR.

Longtime CEO Tim Mayleben, who championed the company for 9 years from early clinical through a lengthy late-stage drive to successfully get their cholesterol drug approved for a significant niche of patients in the US, is out of the C suite, effective immediately. Sheldon Koenig — hired at the end of 2020 with a resume replete with Big Pharma CV sales experience —  is stepping into his place, promising to right a badly listing commercial ship that’s been battered by market forces.

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No­var­tis' En­tresto takes its 2nd fail­ure of the week­end at ACC, show­ing no ben­e­fit in most dire heart fail­ure pa­tients

Novartis’ Entresto started the ACC weekend off rough with a trial flop in heart attack patients, slowing the drug’s push into earlier patients. Now, an NIH-sponsored study is casting doubt on Entresto’s use in the most severe heart failure patients, another black mark on the increasingly controversial drug’s record.

Entresto, a combination of sacubitril and valsartan, could not beat out valsartan alone in an outcomes head-to-head for severe heart failure patients with a reduced ejection fraction (HFrEF), according to data presented Monday at the virtual American College of Cardiology meeting.

Matt Gline (L) and Vivek Ramaswamy

In­sid­er ac­count of Roivan­t's SPAC deal — and that $7.3B val­u­a­tion — re­veals a few se­crets as Matt Gline po­si­tions the com­pa­ny as the new ‘Big Phar­ma’

It was Oct. 7, 2020, and Matt Gline wasn’t wasting any time.

The CEO of Roivant had word that KKR vet Jim Momtazee’s SPAC had priced late the night before, triggering a green light for anyone interested in pursuing a big check for future operations and riding the financial instrument to Nasdaq. So he wrote a quick email congratulating Momtazee, whom he knew, for the launch.

Oh, and maybe Momtazee would like to schedule something with Gline and his executive chairman, Roivant founder Vivek Ramaswamy, to chat about Roivant and its business?

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$DNA is once again on NYSE; FDA clears Soliris chal­lenger for the mar­ket; Flag­ship’s think­ing big again with eR­NA; 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.

I still remember the uncertainty in the air last year when nobody was sure whether ASCO would cancel their in-person meeting. But it’s now back again for the second virtual conference, and Endpoints News is here for it. Check out our 2-day event reviewing the landscape of cancer R&D and send news our way.

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John­son & John­son do­nates Ebo­la vac­cine amid new out­break; Ji Xing promis­es more than $127M for Mile­stone's nasal spray for rapid heart rate

As Johnson & Johnson continues to roll out its Covid-19 shot, the company is also focused on another vaccine.

J&J is donating up to 200,000 doses of its Ebola vaccine regimen developed with Bavarian Nordic to help health authorities deal with a new outbreak in Sierra Leone. The regimen, Zabdeno and Mvabea, was granted prequalification by the WHO in April, which will help accelerate its registration in countries where Ebola is a threat.