Ear­ly snap­shot of Ad­verum's eye gene ther­a­py sparks con­cern about vi­sion loss

An ear­ly-stage up­date on Ad­verum Biotech­nolo­gies’ in­trav­it­re­al gene ther­a­py has trig­gered in­vestor con­cern, af­ter pa­tients with wet age-re­lat­ed mac­u­lar de­gen­er­a­tion (AMD) saw their vi­sion de­te­ri­o­rate, de­spite signs that the treat­ment is im­prov­ing reti­nal anato­my.

Ad­verum, on Wednes­day, un­veiled 24-week da­ta from the OP­TIC tri­al of its ex­per­i­men­tal ther­a­py, AD­VM-022, in six pa­tients who have been ad­min­is­tered with one dose of the ther­a­py. On av­er­age, pa­tients in the tri­al had se­vere dis­ease with an av­er­age of 6.2 an­ti-VEGF in­jec­tions in the eight months pri­or to screen­ing and an av­er­age an­nu­al­ized in­jec­tion fre­quen­cy of 9.3 in­jec­tions.

Over the six month pe­ri­od, pa­tients did not re­quire any an­ti-VEGF res­cue in­jec­tions — and five of six pa­tients saw a com­plete re­sponse with a to­tal res­o­lu­tion of flu­id fol­low­ing the Ad­verum in­jec­tion. There were no se­ri­ous ad­verse events, and the ma­jor­i­ty of side-ef­fects were mild.

How­ev­er, pa­tients lost vi­su­al acu­ity by two let­ters on av­er­age, with a 90% con­fi­dence in­ter­val of -9.1 let­ters to +5.1 let­ters.

Mani Foroohar

“The range of in­di­vid­ual pa­tient da­ta were not pre­sent­ed, though the wide con­fi­dence in­ter­val sug­gests that some pa­tients may have ex­pe­ri­enced a loss of more than 10 let­ters dur­ing the course of the tri­al – lack of res­cue in­jec­tions is dif­fi­cult to square with de­clin­ing vi­sion.” SVB Leerink’s Mani Foroohar wrote in a note.

“How­ev­er, the study in­ves­ti­ga­tor in­sist­ed no loss in vi­sion was due to wet AMD pathol­o­gy and ob­served loss of vi­su­al acu­ity is due to nor­mal vari­abil­i­ty…in a small set of pa­tients – an as­ser­tion that, if proved out with ad­di­tion­al fol­low-up, would very sub­stan­tial­ly im­prove the im­plied qual­i­ty of this dataset.”

Shares of the com­pa­ny — which spec­tac­u­lar­ly failed years ago when it was chris­tened Avalanche Biotech­nolo­gies — $AD­VM were down about 6.8% to $5.56 in Fri­day pre­mar­ket trad­ing. The stock sank on Thurs­day, evap­o­rat­ing mil­lions from its mar­ket val­ue.

“This da­ta sug­gest AD­VM-022 is po­ten­tial­ly ac­tive in de­liv­er­ing an ex­press­ible gene cas­sette in wet AMD, but mixed sig­nals in this small dataset should lift some of the com­pet­i­tive over­hang on RGNX shares,” Foroohar added. Re­genexBio ex­per­i­men­tal gene ther­a­py for wet AMD, RGX-314, is cur­rent­ly in a Phase I/II tri­al.

Wet AMD, which is char­ac­ter­ized by blurred vi­sion or a blind spot in an in­di­vid­ual’s vi­su­al field, is typ­i­cal­ly caused by ab­nor­mal growth of blood ves­sels that leak flu­id or blood in­to the mac­u­la. Mac­u­lar de­gen­er­a­tion is the lead­ing cause of se­vere, ir­re­versible vi­sion loss in the el­der­ly. An­ti-VEGF in­jec­tions such as Re­gen­eron’s $REGN flag­ship Eylea, as well as Roche’s $RHB­BY Lu­cen­tis and Avastin, are com­mon­ly used to treat wet AMD.

In April, the FDA im­posed a clin­i­cal hold on an ap­pli­ca­tion to test AD­VM-022 in hu­mans, ask­ing for ad­di­tion­al da­ta on Ad­verum’s chem­istry, man­u­fac­tur­ing and con­trol process. In May, the hold was lift­ed. Late last year, the biotech aban­doned its then lead ex­per­i­men­tal drug, AD­VM-043, for the treat­ment of A1AT de­fi­cien­cy.

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.

Illustration: Assistant Editor Kathy Wong for Endpoints News

As mon­ey pours in­to dig­i­tal ther­a­peu­tics, in­sur­ance cov­er­age crawls



Talk therapy didn’t help Lily with attention deficit hyperactivity disorder, or ADHD. But a video game did.

As the 10-year-old zooms through icy waters and targets flying creatures on the snow-capped planet Frigidus, she builds attention skills, thanks to Akili Interactive Labs’ video game EndeavorRx. She’s now less anxious and scattered, allowing her to stay on a low dose of ADHD medication, according to her mom Violet Vu.

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Eli Lil­ly’s Alzheimer’s drug clears more amy­loid ear­ly than Aduhelm in first-ever head-to-head. Will it mat­ter?

Ahead of the FDA’s decision on Eli Lilly’s Alzheimer’s drug donanemab in February, the Big Pharma is dropping a first cut of data from one of the more interesting trials — but less important in a regulatory sense — at an Alzheimer’s conference in San Francisco.

In the unblinded 148-person study, Eli Lilly pitted its drug against Aduhelm, Biogen’s drug that won FDA approval but lost Medicare coverage outside of clinical trials. Notably, the study didn’t look at clinical outcomes, but rather the clearance of amyloid, a protein whose buildup is associated with Alzheimer’s disease, in the brain.

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Matt Gline, Roivant Sciences CEO (Photo by John Sciulli/Getty Images for GLG)

Pfiz­er and Roivant team up again for an­oth­er 'Van­t', set­ting up an­ti-in­flam­ma­to­ry show­down with Prometheus

Pfizer and Roivant are teaming up to launch a new ‘Vant’ aimed at bringing a mid-stage anti-inflammatory drug to market, the pair announced Thursday.

There’s no name for the startup yet, nor are there any employees. Thus far, the new company and Roivant can be considered “one and the same,” Roivant CEO Matt Gline tells Endpoints News. But Pfizer is so enthusiastic about the target that it elected to keep 25% of equity in the drug rather than take upfront cash from Roivant, Gline said.

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Roche HQ in Basel, Switzerland. (Image credit: Kyle LaHucik/Endpoints News)

As com­peti­tors near FDA goal­post, Roche spells out its re­peat Alzheimer's set­back

Before Roche can turn all eyes on a new version of its more-than-once-failed Alzheimer’s drug gantenerumab, the Big Pharma had to flesh out data on the November topline failure at an annual conference buzzier than in years past thanks to hotly watched rivals in the field: Eisai and Biogen’s lecanemab, and Eli Lilly’s donanemab.

There was less than a 10% difference between Roche’s drug and placebo at slowing cognitive decline across two Phase III trials, which combined enrolled nearly 2,000 Alzheimer’s patients. In its presentation at the conference Wednesday, Roche said it saw less sweeping away of toxic proteins than it had anticipated. For years, researchers and investors have put their resources behind the idea that more amyloid removal would equate to reduced cognitive decline.

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SQZ Biotech slash­es head­count by 60% as founder/CEO hits ex­it — while Syn­log­ic lays off 25%

It’s a tough time for early-stage companies developing highly promising, but largely unproven, new technologies.

Just ask SQZ Biotechnologies and Synlogic. The former is bidding farewell to its founder and CEO and slashing the headcount by 60% as it pivots from its original cell therapy platform to a next-gen approach; the latter — a synthetic biology play founded by MIT’s Jim Collins and Tim Lu — is similarly “optimizing” the company to focus on lead programs. The resulting realignment means 25% of the staffers will be laid off.

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Ei­sai’s ex­pand­ed Alzheimer’s da­ta leave open ques­tions about safe­ty and clin­i­cal ben­e­fit

Researchers still have key questions about Eisai’s investigational Alzheimer’s drug lecanemab following the publication of more Phase III data in the New England Journal of Medicine Tuesday night.

In the paper, which was released in conjunction with presentations at an Alzheimer’s conference, trial investigators write that a definition of clinical meaningfulness “has not been established.” And the relative lack of new information, following topline data unveiled in September, left experts asking for more — setting up a potential showdown to precisely define how big a difference the drug makes in patients’ lives.

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Paul Hudson, Sanofi CEO (Romuald Meigneux/Sipa via AP Images)

Sanofi and DN­Di aim to elim­i­nate sleep­ing sick­ness in Africa with promis­ing Ph II/III re­sults for new drug

The Drugs for Neglected Diseases initiative (DNDi) and Sanofi today said that their potential sleeping sickness treatment saw success rates of up to 95% from a Phase II/III study investigating the safety and efficacy of single-dose acoziborole.

The potentially transformative treatment for sleeping sickness would mainly be targeted at African countries, according to data published today in The Lancet Infectious Diseases medical journal. The clinical trial was led by DNDi and its partners in the Democratic Republic of the Congo (DRC) and Guinea, with the authors noting:

Lynn Baxter, Viiv Healthcare's head of North America

Vi­iV dri­ves new cor­po­rate coali­tion in­clud­ing Uber, Tin­der and Wal­mart, aimed at end­ing HIV

ViiV Healthcare is pulling together an eclectic coalition of consumer businesses in a new White House-endorsed effort to end HIV by the end of the decade.

The new US Business Action to End HIV includes pharma and health companies — Gilead Sciences, CVS Health and Walgreens — but extends to a wide range of consumer companies that includes Tinder, Uber and Walmart.

ViiV is the catalyst for the group, plunking down more than half a million dollars in seed money and taking on ringmaster duties for launch today on World AIDS Day, but co-creator Health Action Alliance will organize joint activities going forward. ViiV and the alliance want and expect more companies to not only join the effort, but also pitch in funding.

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