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.

2023 Spot­light on the Fu­ture of Drug De­vel­op­ment for Small and Mid-Sized Biotechs

In the context of today’s global economic environment, there is an increasing need to work smarter, faster and leaner across all facets of the life sciences industry.  This is particularly true for small and mid-sized biotech companies, many of which are facing declining valuations and competing for increasingly limited funding to propel their science forward.  It is important to recognize that within this framework, many of these smaller companies already find themselves resource-challenged to design and manage clinical studies themselves because they don’t have large teams or in-house experts in navigating the various aspects of the drug development journey. This can be particularly challenging for the most complex and difficult to treat diseases where no previous pathway exists and patients are urgently awaiting breakthroughs.

Rick Modi, Affinia Therapeutics CEO

Ver­tex-part­nered gene ther­a­py biotech Affinia scraps IPO plans

Affinia Therapeutics has ditched its plans to go public in a relatively closed-door market that has not favored Nasdaq debuts for the drug development industry most of this year. A pandemic surge in 2020 and 2021 opened the doors for many preclinical startups, which caught Affinia’s attention and gave the gene therapy biotech confidence in the beginning days of 2022 to send in its S-1.

But on Friday, Affinia threw in the S-1 towel and concluded now is not the time to step onto Wall Street. The biotech has put out few public announcements since the spring of this year. Endpoints News picked the startup as one of its 11 biotechs to watch last year.

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Up­dat­ed: FDA re­mains silent on or­phan drug ex­clu­siv­i­ty af­ter last year's court loss

Since losing a controversial court case over orphan drug exclusivity last year, the FDA’s Office of Orphan Products Development has remained entirely silent on orphan exclusivity for any product approved since last November, leaving many sponsors in limbo on what to expect.

That silence means that for more than 70 orphan-designated indications for more than 60 products, OOPD has issued no public determination on the seven-year orphan exclusivity in the Orange Book, and no new listings of orphan exclusivity appear in OOPD’s searchable database, as highlighted recently by George O’Brien, a partner in Mayer Brown’s Washington, DC office.

Albert Bourla, Pfizer CEO (Efren Landaos/Sipa USA/Sipa via AP Images)

Pfiz­er makes an­oth­er bil­lion-dol­lar in­vest­ment in Eu­rope and ex­pands again in Michi­gan

Pfizer is continuing its run of manufacturing site expansions with two new large investments in the US and Europe.

The New York-based pharma giant’s site in Kalamazoo, MI, has seen a lot of attention over the past year. As a major piece of the manufacturing network for Covid-19 vaccines and antivirals, Pfizer is gearing up to place more money into the site. Pfizer announced it will place $750 million into the facility, mainly to establish “modular aseptic processing” (MAP) production and create around 300 jobs at the site.

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Vas Narasimhan, Novartis CEO (Thibault Camus/AP Images, Pool)

No­var­tis bol­sters Plu­vic­to's case in prostate can­cer with PhI­II re­sults

The prognosis is poor for metastatic castration-resistant prostate cancer (mCRPC) patients. Novartis wants to change that by making its recently approved Pluvicto available to patients earlier in their course of treatment.

The Swiss pharma giant unveiled Phase III results Monday suggesting that Pluvicto was able to halt disease progression in certain prostate cancer patients when administered after androgen-receptor pathway inhibitor (ARPI) therapy, but without prior taxane-based chemotherapy. The drug is currently approved for patients after they’ve received both ARPI and chemo.

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Nkarta CEO Paul Hastings at Endpoints' #BIO22 panel (J.T. MacMillan Photography for Endpoints News)

Nkar­ta un­der­scores safe­ty of CAR-NK, boasts ear­ly re­spons­es

The first generation of personalized CAR-T therapies made big waves in the treatment of lymphoma for their stunning efficacy. Nkarta is hoping its off-the-shelf natural killer cell approach will stand out on safety — while keeping some of those impressive numbers on responses.

In a new update from its Phase I dose escalation study, the South San Francisco-based biotech reported that seven out of 10 patients treated with the highest doses of its NK cell therapy, NKX019, achieved a complete response, translating to a complete response rate of 70%.

Ken Greenberg, SonoThera CEO

Gene ther­a­py goes acoustic as ARCH-backed biotech launch­es with ul­tra­sound gene de­liv­ery plat­form

After co-founding two biotechs off virus-based therapies, one for pain and one for cancer, Ken Greenberg decided to go in a different direction for his newest biotech, SonoThera.

Based out of San Francisco, SonoThera announced Monday morning that it raised $60.75 million to develop new gene therapies — but delivered by ultrasound, which Greenberg says can address the major challenges facing more conventional viral gene therapies.

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Af­ter M&A fell through, Ther­a­peu­tic­sMD sells hor­mone ther­a­py, con­tra­cep­tive ring for $140M cash plus roy­al­ties

TherapeuticsMD, a women’s health company whose one-time billion-dollar valuation seems a distant memory as its blockbuster aspirations petered out, is finally cashing out.

Australia’s Mayne Pharma is paying $140 million upfront to license essentially TherapeuticsMD’s whole portfolio, including two prescription drugs that treat conditions relating to menopause, a contraceptive vaginal ring as well as its prescription prenatal vitamin brands.

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Big week for Alzheimer’s da­ta; As­traZeneca buys cell ther­a­py start­up; Dig­i­tal ther­a­peu­tics hits a pay­er wall; 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.

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