Aer­pio shares tum­ble as lead eye drug trips up in mid-stage di­a­bet­ic retinopa­thy study

Rough­ly two years af­ter rais­ing $40 mil­lion in a pri­vate place­ment, Aer­pio Phar­ma­ceu­ti­cals’ lead ex­per­i­men­tal eye drug has hit a road­block af­ter fail­ing a mid-stage study in pa­tients with non-pro­lif­er­a­tive di­a­bet­ic retinopa­thy (NPDR) — the ear­li­est stage of di­a­bet­ic eye dis­ease, which oc­curs when high blood sug­ar lev­els cause dam­age to blood ves­sels in the reti­na.

Stephen Hoff­man

These blood ves­sels can swell and leak, or close re­strict­ing blood flow and even­tu­al­ly cul­mi­nate in blind­ness. In the 167-pa­tient tri­al, called TIME-2b, pa­tients were giv­en the drug — AKB-9778 —  (once or twice dai­ly) or place­bo (once or twice dai­ly) for 48 weeks. The main goal was to im­prove the the study eye di­a­bet­ic retinopa­thy sever­i­ty score (DRSS) by two or more steps com­pared to the place­bo.

Ad­min­is­tra­tion of AKB-9778 twice dai­ly missed the study’s pri­ma­ry end­point, the com­pa­ny said on Mon­day. Shares of the Cincin­nati-based drug de­vel­op­er $AR­PO cratered more than 68% to $1.36 in pre-mar­ket trad­ing.

About 9.6% of pa­tients giv­en AKB-9779 twice dai­ly ex­pe­ri­enced such an im­prove­ment, ver­sus 3.8% on the place­bo — draw­ing a less than rosy p val­ue (p=0.270). The rates of pro­gres­sion to sight-threat­en­ing com­pli­ca­tions, in­clud­ing di­a­bet­ic mac­u­lar ede­ma (DME) and/or pro­lif­er­a­tive di­a­bet­ic retinopa­thy (PDR), dur­ing the treat­ment pe­ri­od were sim­i­lar be­tween treat­ment groups, Aer­pio not­ed, adding that the use of the ex­per­i­men­tal drug had an “en­cour­ag­ing” im­pact on key sec­ondary goals, in­clud­ing a mea­sure of kid­ney func­tion and in­traoc­u­lar pres­sure.

Un­like pa­tients with di­a­bet­ic eye dis­ease who are typ­i­cal­ly giv­en an­ti-VEGF in­jec­tions in­to the eye, AKB-9778 is self-ad­min­is­tered sub­cu­ta­neous­ly by the pa­tient, akin to in­sulin. The ex­per­i­men­tal drug is a small mol­e­cule in­hibitor of VE-PTP, the most crit­i­cal neg­a­tive reg­u­la­tor of Tie2 — a path­way be­lieved to sta­bi­lize vas­cu­la­ture — in dis­eased blood ves­sels. In a sep­a­rate study, called TIME-2, AKB-9778 im­proved un­der­ly­ing symp­toms by two or more steps on a di­a­bet­ic retinopa­thy sever­i­ty scale in both eyes.

Un­de­terred by the TIME-2b fail­ure, Aer­pio chief Stephen Hoff­man ex­pressed en­thu­si­asm for the to­tal­i­ty of da­ta on the drug. “(C)ol­lec­tive­ly these da­ta sup­port a po­ten­tial­ly im­por­tant role of the Tie2 path­way for the treat­ment of di­a­bet­ic com­pli­ca­tions, as well as for open an­gle glau­co­ma,” he said in a state­ment, adding that a Phase Ib study of a top­i­cal drop for­mu­la­tion of AKB-9778 is ex­pect­ed to com­mence in the sec­ond quar­ter.

Aer­pio al­so has an­oth­er ex­per­i­men­tal eye drug in de­vel­op­ment, in ad­di­tion to an in­ves­ti­ga­tion­al ther­a­py for in­flam­ma­to­ry bow­el dis­ease.

Lessons for biotech and phar­ma from a doc­tor who chased his own cure

After being struck by a rare disease as a healthy third year medical student, David Fajgenbaum began an arduous journey chasing his own cure. Amidst the hustle of this year’s JP Morgan conference, the digital trials platform Medable partnered with Endpoints Studio to share Dr. Fajgenbaum’s story with the drug development industry.

What follows is an edited transcript of the conversation between Medable CEO Dr. Michelle Longmire and Dr. Fajgenbaum, and it is full of lessons for biotech executives charged with bringing the next generation of medicines to patients.

Jim Scholefield via PR Newswire

Mer­ck los­es its chief dig­i­tal of­fi­cer, spot­light­ing tal­ent hunt for the hottest ti­tle in Big Phar­ma

Over the last few years we’ve seen the chief digital officer title become one of the hottest commodities in Big Pharma as global organizations hunt the best talent to sharpen the cutting edge of their tech platforms.

But Merck just discovered how hard it may be to keep them focused on pharma.

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Kathy High (file photo)

Gene ther­a­py pi­o­neer Kathy High has left Spark af­ter com­plet­ing $4.3B union with Roche

Kathy High dedicated the past seven years of her life shepherding experimental gene therapies she’s developed at Children’s Hospital of Philadelphia toward the market as president and head of R&D at Spark Therapeutics. Now that the biotech startup is fully absorbed into Roche — with an FDA approval, a $4.3 billion buyout and a promising hemophilia program to boast — she’s ready to move on.

Roche confirmed her departure with Endpoints News and noted “she will take some well-deserved time off and then will begin a new chapter in a sabbatical at a university.”

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Tal Zaks (Moderna via YouTube)

For two decades, a new vac­cine tech­nol­o­gy has been slow­ly ap­proach­ing prime time. Now, can it stop a pan­dem­ic?

Two months before the outbreak, Moderna CMO Tal Zaks traveled from Cambridge, MA to Washington DC to meet with Anthony Fauci and the leaders of the National Institutes of Health.

For two years, Moderna had worked closely with NIH researchers to build a new kind of vaccine for MERS, one of the deadliest new viruses to emerge in the 21st century. The program was one test for a new technology designed to be faster, cheaper and more precise than the ways vaccines had been made for over a century. They had gathered evidence the technology could work in principle, and Fauci, the longtime head of the National Institute of Allergy and Infectious Diseases and a longtime advocate for better epidemic preparedness, wanted to see if it, along with a couple of other approaches, could work in a worst-case scenario: A pandemic.

“[We were] trying to find a test case for how to demonstrate if our technology could rapidly prepare,” Zaks told Endpoints News.

Zaks and Fauci, of course, wouldn’t have to wait to develop a new test. By year’s end, an outbreak in China would short circuit the need for one and throw them into 24/7 work on a real-world emergency. They also weren’t the only ones with new technology who saw a chance to help in a crisis.

An ocean away, Lidia Oostvogels was still on vacation and relaxing at her mother’s house in Belgium when her Facebook started changing. It was days after Christmas and on most people’s feeds, the news that China had reported a novel virus to the World Health Organization blurred into the stream of holiday sweaters and fir trees. But on Oostvogels’s feed, full of vaccine researchers and virus experts, speculation boiled: There was a virus in China, something contained to the country, but “exotic,” “weird,” and maybe having to do with animals. Maybe a coronavirus.

Lidia Oostvogels

“I was immediately thinking like, ‘Hey, this is something that if needed, we can play a role,'” Oostvogels told Endpoints.

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Say good­bye to Toca­gen, strug­gling brain can­cer biotech to re­verse merge with Forte Bio­sciences

Five months after a huge Phase III failure triggered mass layoffs at the company, Tocagen will sign itself out of existence.

The biotech, once focused on brain cancer, announced it has signed a reverse merger agreement with Forte Biosciences, a biotech tackling atopic dermatitis and other inflammatory skin diseases. Tocagen’s stock shot up 85% on the news, although that only translated to a 41-cent bump for a company that saw the last of its value go poof in September. The new company will trade under the ticker $FBRX.

JJ Bienaimé (BioMarin via YouTube)

Speedy re­view and no ad­comm for Bio­Mar­in's pi­o­neer­ing he­mo­phil­ia gene ther­a­py

BioMarin’s keenly anticipated hemophilia A gene therapy — which CEO JJ Bienaimé envisions pricing at an eye-watering $2 million to $3 million a shot — has secured red carpet treatment at the FDA.

The therapy, fondly called valrox, has won priority review — and there the agency has indicated there are no plans for an advisory committee meeting. The US regulator’s final decision is expected by August 21. If approved, it will be the pioneering gene therapy for hemophilia.

“While the company…indicated that FDA does not currently plan on convening an advisory committee meeting to discuss the merits of the application, we caution that the possibility of such still remains as the agency digs into its review, which could be interpreted negatively by the Street,” BMO Capital Market’s George Farmer wrote.

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Christos Kyratsous (via LinkedIn)

He built a MERS treat­ment in 6 months and then the best Ebo­la drug. Now Chris­tos Kyrat­sous turns his sights on Covid-19

TARRYTOWN, NY — In 2015, as the Ebola epidemic raged through swaths of West Africa, Kristen Pascal’s roommates sat her down on their couch and staged an intervention.

“Are you sure this is what you want to be doing with your life?” she recalls them asking her.

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Pascal, a research associate for Regeneron, had been coming home at 2 am and leaving at 6 am. At one point, she didn’t see her roommate for a week. For months, that was life in Christos Kyratsous’ lab as the pair led a company-wide race to develop the first drug that could effectively treat Ebola before the outbreak ended. For Pascal, that was worth it.

“I’m ok, I don’t have Ebola,” Pascal told them. “I see that death toll rising and I can’t not do something about it.”

Last August, Regeneron learned they had succeeded: In a large trial across West Africa, their drug, REGN-EB3, was vastly more effective than the standard treatments. It was surprise news for the company, coming just 10 months into a trial they thought would take several years and a major victory in the global fight against a deadly virus that killed over 2,000 in 2019 and can carry a mortality rate of up to 90%.

For Kyratsous and Pascal, though, it brought only fleeting reprieve. Just four months after the NIH informed them REGN-EB3 worked, Kyratsous was back in his office reading the New York Times for updates on a new outbreak on another continent, and wondering alongside Pascal and senior management whether it was time to pull the trigger again.

In late January, as the death toll swelled and the first confirmed cases outside China broke double digits, they made a decision. Soon they were back on the phone with the multiple government agencies and their coronavirus partners at the University of Maryland’s Level 3 bio lab. The question was simple: Can Kyratsous and his team use a process honed over two previous outbreaks, and create a treatment before the newest epidemic ends? Or worse, if, as world health experts fear, it doesn’t vanish but becomes a recurrent virus like the flu?

“Christos likes things immediately,” Matt Frieman, Regeneron’s coronavirus collaborator at the University of Maryland, told Endpoints. “That’s what makes us good collaborators: We push each other to develop things faster and faster.”

Kristen Pascal (Regeneron)

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The first time Regeneron tried to respond to a global outbreak, it was something of a systems test, Kyratsous explains from his office at Regeneron’s Tarrytown headquarters. Kyratsous, newly promoted, has crammed it with photos of his family, sketches of viral vectors and a shark he drew for his 3-year-old son. He speaks rapidly – an idiosyncrasy his press person says has only been aggravated this afternoon by the contents of his “Regeneron Infectious Diseases”-minted espresso glass – and he gesticulates with similar fluidity, tumbling through antibodies, MERS, the novel coronavirus, Ebola-infected monkeys.

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Phar­ma­co­ge­net­ics: FDA re­leas­es ta­ble of gene-drug in­ter­ac­tions

The FDA on Thursday published a table identifying more than 50 gene-drug interactions that the agency says are supported by scientific evidence and announced it is considering new approaches to evaluating pharmacogenetic associations.

“Consistent with our mission to protect and promote public health, we believe it is important to take steps now to help ensure that claims being made for pharmacogenetic tests offered today are grounded in sound science to avoid inappropriate management of patients’ medications,” said Center for Devices and Radiological Health Director Jeff Shuren and Center for Drug Evaluation and Research Director Janet Woodcock.

Don't let Ab­b­Vie fool FTC with an easy di­vesti­ture, plead crit­ics in lat­est at­tack on $63B Al­ler­gan buy­out

If the FTC must let AbbVie and Allergan go ahead with their merger, at least make them divest their latest blockbuster on the market, a chorus of unions, consumer groups and public interest organizations plead in a new attempt to rein in the megamerger.

There’s a second part to their argument: If the antitrust watchdog does greenlight the divestiture AbbVie wants, then at least ensure the pharma giant cannot corner its future rivals with its exclusionary tactics.

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