Avidity Biosciences CSO Art Levin and CEO Sarah Boyce

FDA slaps a par­tial hold on Avid­i­ty's mAb-siR­NA ther­a­py, paus­ing en­roll­ment in mus­cle weak­ness dis­ease study

Avid­i­ty Bio­sciences will have to wait to en­roll new pa­tients in a Phase I/II study of its ther­a­py for my­oton­ic dy­s­tro­phy type 1, or DM1, which weak­ens mus­cles and leads to res­pi­ra­to­ry and car­diac is­sues.

The FDA is dock­ing new en­roll­ment in the MA­RI­NA study as the com­pa­ny and one of its tri­al in­ves­ti­ga­tors look in­to a se­ri­ous ad­verse event re­port­ed in a pa­tient in the 4 mg/kg co­hort, the biotech said Tues­day morn­ing. Pa­tients cur­rent­ly en­rolled can con­tin­ue on the study drug or place­bo and roll over in­to the open-la­bel ex­ten­sion.

On an in­vestor call, ex­ec­u­tives re­peat­ed­ly de­clined to de­scribe the ad­verse event, when it oc­curred or the sta­tus of the pa­tient, cit­ing pri­va­cy con­cerns. Asked if the pa­tient was still alive, the com­pa­ny said yes.

Cowen an­a­lysts wrote in a note that the pa­tient was in the hos­pi­tal for tests and has since been dis­charged home. “While oc­cur­rence of the SAE is un­for­tu­nate, we find the lack of clar­i­ty on the event it­self and its tim­ing more frus­trat­ing,” the an­a­lysts wrote, not­ing they view the par­tial hold as “like­ly re­solv­able.”

Avid­i­ty’s shares $RNA slid about 16% af­ter the open­ing bell Tues­day.

Steve Hugh­es

Med­ical chief Steve Hugh­es said the biotech doesn’t be­lieve the events are re­lat­ed to the plat­form or the tar­get. The drug, dubbed AOC 1001, com­pris­es a mon­o­clon­al an­ti­body that binds to trans­fer­rin re­cep­tor 1, TfR, that is con­ju­gat­ed with a small in­ter­fer­ing RNA, or siR­NA. The goal is to re­duce the amount of my­oton­ic dy­s­tro­phy pro­tein ki­nase (DMPK) RNA.

The tar­get, TfR, is al­so in­volved in Dyne Ther­a­peu­tics’ Duchenne mus­cu­lar dy­s­tro­phy drug DYNE-251 and De­nali Ther­a­peu­tics’ Alzheimer’s ther­a­py DNL919, both side­lined by the FDA ear­li­er this year. The agency cleared Dyne’s tri­al in the sum­mer, and De­nali said last month it’s now test­ing the drug in the Nether­lands.

Hugh­es said the San Diego biotech doesn’t be­lieve the event is re­lat­ed to DMPK knock­down, ei­ther. The com­pa­ny is work­ing with the in­ves­ti­ga­tor on more test­ing and gath­er­ing more in­for­ma­tion about the pa­tient’s med­ical and fam­i­ly his­to­ry “to de­ter­mine what is the most like­ly un­der­ly­ing cause for the event that we’ve seen,” the CMO said on the in­vestor call.

The pa­tient was part of the 4 mg/kg co­hort, which in­cludes about 18 of the near­ly 40 pa­tients en­rolled thus far, CEO and pres­i­dent Sarah Boyce said on the call. The study aims to en­roll 44 pa­tients, ac­cord­ing to a fed­er­al tri­als data­base, and Boyce said the en­roll­ment num­bers aren’t ex­pect­ed to change. There are al­so no plans at the mo­ment to change in­clu­sion cri­te­ria, she said in re­sponse to ques­tions on the con­fer­ence call.

The 4 mg/kg dose is “ap­prox­i­mate­ly an or­der of mag­ni­tude low­er than dos­es that we’ve used in tox stud­ies,” chief sci­en­tif­ic of­fi­cer Art Levin said dur­ing the call.

It’s the dose that will like­ly pack the most punch.

“Those tox stud­ies have ex­tend­ed to nine months of du­ra­tion where the high­est dose used was es­sen­tial­ly the no ad­verse ef­fect lev­el, so we have a sig­nif­i­cant safe­ty mar­gin to pro­vide es­ca­la­tion. But again the da­ta that we found in non­clin­i­cal stud­ies would sug­gest that the knock­down that we pro­duce at the dose of 4 mg/kg would be close to the max­i­mal knock­down that we can achieve,” Levin con­tin­ued.

DM1 af­fects more than 40,000 peo­ple in the US, where there is no ap­proved ther­a­py. Pre­lim­i­nary safe­ty, tol­er­a­bil­i­ty and bio­mark­er da­ta for about half of the study en­rollees will be re­leased next quar­ter.

As new en­roll­ment in the MA­RI­NA study gets held up, the com­pa­ny is mov­ing in­to the clin­ic with two oth­er treat­ments: AOC 1020 for fa­cioscapu­lo­humer­al mus­cu­lar dy­s­tro­phy (FSHD) and AOC 1044  for Duchenne mus­cu­lar dy­s­tro­phy (DMD) with mu­ta­tions amenable to ex­on 44 skip­ping.

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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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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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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Vi­a­tris with­draws ac­cel­er­at­ed ap­proval for top­i­cal an­timi­cro­bial 24 years lat­er

After 24 years without confirming clinical benefit, the FDA announced Tuesday morning that Viatris (formed via Mylan and Pfizer’s Upjohn) has decided to withdraw a topical antimicrobial agent, Sulfamylon (mafenide acetate), after the company said conducting a confirmatory study was not feasible.

Sulfamylon first won FDA’s accelerated nod in 1998 as a topical burn treatment, with the FDA noting that last December, Mylan told the agency that it wasn’t running the trial.

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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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