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.

Secretary of health and human services Alex Azar speaking in the Rose Garden at the White House (Photo: AFP)

Trump’s HHS claims ab­solute au­thor­i­ty over the FDA, clear­ing path to a vac­cine EUA

The top career staff at the FDA has vowed not to let politics overrule science when looking at vaccine data this fall. But Alex Azar, who happens to be their boss’s boss, apparently won’t even give them a chance to stand in the way.

In a new memorandum issued Tuesday last week, the HHS chief stripped the FDA and other health agencies under his purview of their rule making ability, asserting all such power “is reserved to the Secretary.” Sheila Kaplan of the New York Times first obtained and reported the details of the September 15 bulletin.

#ES­MO20: Push­ing in­to front­line, Mer­ck and Bris­tol My­ers duke it out with new slate of GI can­cer da­ta

Having worked in parallel for years to move their respective PD-1 inhibitors up to the first-line treatment of gastrointestinal cancers, Merck and Bristol Myers Squibb finally have the data at ESMO for a showdown.

Comparing KEYNOTE-590 and CheckMate-649, of course, comes with the usual caveats. But a side-by-side look at the overall survival numbers also offer some perspective on a new frontier for the reigning checkpoint rivals, both of whom are claiming to have achieved a first.

President Donald Trump (via AP Images)

Signs of an 'Oc­to­ber Vac­cine Sur­prise' alarm ca­reer sci­en­tists

President Donald Trump, who seems intent on announcing a COVID-19 vaccine before Election Day, could legally authorize a vaccine over the objections of experts, officials at the FDA and even vaccine manufacturers, who have pledged not to release any vaccine unless it’s proved safe and effective.

In podcasts, public forums, social media and medical journals, a growing number of prominent health leaders say they fear that Trump — who has repeatedly signaled his desire for the swift approval of a vaccine and his displeasure with perceived delays at the FDA — will take matters into his own hands, running roughshod over the usual regulatory process.

#ES­MO20: Bris­tol My­ers marks Op­di­vo's sec­ond ad­ju­vant win — eye­ing a stan­dard of care gap

Moving into earlier and earlier treatment lines, Bristol Myers Squibb is reporting that adjuvant treatment with Opdivo has doubled the time that esophageal or gastroesophageal junction cancer patients stay free of disease.

With the CheckMate-577 data at ESMO, CMO Samit Hirawat said, the company believes it can change the treatment paradigm.

While a quarter to 30% of patients typically achieve a complete response following chemoradiation therapy and surgery, the rest do not, said Ronan Kelly of Baylor University Medical Center. The recurrence rate is also high within the first year, Hirawat added.

Clay Siegall (Life Science Washington via YouTube)

#ES­MO20: Seat­tle Ge­net­ics eyes 4th ap­proval with new da­ta in a crowd­ed field

Does Seattle Genetics have another approval on its hands?

The last 12 months, not so great for the world, has been great for Seattle Genetics. The company landed two separate FDA approvals, signed a $4.5 billion deal with Merck and watched antibody-drug conjugates — the technology they spent years developing to broad industry skepticism — emerge suddenly as one of the most popular approaches in oncology. And on Monday at ESMO, the company and their partners at Genmab unveiled the data behind the ADC it hopes will provide its next major FDA approval.

Jonathan Rigby, Immune Regulation group CEO

Im­mune Reg­u­la­tion, tak­ing two clin­i­cal pro­grams to 're­set' the im­mune sys­tem, nets $53M+ Se­ries B

A little under two years after a company rebranding, Immune Regulation is taking an even bigger step toward advancing its goals.

Formerly known as Peptinnovate, the British biotech announced a $53.4 million Series B early Monday morning, helping to further advance two clinical programs in rheumatoid arthritis and asthma. Though those are the two initial indications the company is focusing on, CEO Jonathan Rigby told Endpoints News he hopes the candidates can be applied to a broad swath of autoimmune disorders.

Frank Zhang (AP Images)

Rocked by cus­toms in­ves­ti­ga­tion, Leg­end's CFO takes over as CEO Frank Zhang placed un­der house ar­rest

When Frank Zhang stepped down from GenScript — the contract research group he’s run for 18 years — to take up the CEO post at its CAR-T focused spinout Legend Biotech, he assured analysts that he was in for the long haul.

Just 49 days later, though, he’s been forced to hand back the title.

In a dramatic turn of events, Legend disclosed that Zhang is under house arrest in China as part of a customs investigation involving GenScript. While he remains the chairman, CFO Ying Huang has been tapped to double as interim CEO.

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Eli Lilly CSO Dan Skovronsky (file photo)

UP­DAT­ED: #ES­MO20: Eli Lil­ly shows off the da­ta for its Verzenio suc­cess. Was it worth $18 bil­lion?

The press release alone, devoid of any number except for the size of the trial, added nearly $20 billion to Eli Lilly’s market cap back in June. Now investors and oncologists will get to see if the data live up to the hype.

On Sunday at ESMO, Eli Lilly announced the full results for its Phase III MonarchE trial of Verzenio, showing that across over 5,000 women who had had HR+, HER2- breast cancer, the drug reduced the odds of recurrence by 25%. That meant 7.8% of the patients on the drug arm saw their cancers return within 2 years, compared with 11.3% on the placebo arm.

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Greg Friberg (File photo)

#ES­MO20: Am­gen team nails down sol­id ear­ly ev­i­dence of AMG 510’s po­ten­tial for NSCLC, un­lock­ing the door to a wave of KRAS pro­grams

The first time I sat down with Amgen’s Greg Friberg to talk about the pharma giant’s KRAS G12C program for sotorasib (AMG 510) at ASCO a little more than a year ago, there was high excitement about the first glimpse of efficacy from their Phase I study, with 5 of 10 evaluable non-small cell lung cancer patients demonstrating a response to the drug.

After decades of failure targeting KRAS, sotorasib offered the first positive look at a new approach that promised to open a door to a whole new approach by targeting a particular mutation to a big target that had remained “undruggable” for decades.

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