, a commercial stage medical technology company focused on designing, developing, and marketing products that improve the quality of life for patients who suffer from neurohealth disorders, today announced that Keith Sullivan, President and Chief Executive Officer, and Steve Furlong, Senior Vice President, Chief Financial Officer, and Treasurer, will participate in the Piper Sandler 34th Annual Healthcare Conference on Thursday, December 1, 2022. The Company is scheduled to present at the conference at 9:30 am Eastern Time the same day via webcast.
A live audio webcast of the conference presentation will be available online at the investor relations page of the Company's website at ir.neuronetics.com. A replay of the webcast will be archived on the website for approximately 90 days.
Current leader, Vaxxinity, will have to convince its doubters if it is to hook a partner.
For those who still believe that targeting amyloid has a role to play in the treatment of Alzheimer’s disease, a new crop of anti-amyloid vaccines promises greater convenience and lower cost than the antibodies that have so far dominated Alzheimer’s research.
Earlier attempts to develop Alzheimer’s vaccines did not succeed, and this approach is for good reason considered a long shot. But the likes of Vaxxinity, Grifols and AC Immune reckon that, this time, things could be different. Vaxxinity is in the lead, and is looking for a partner to take its contender, UB-311, into phase 2b.
While Evercore ISI analysts describe Vaxxinity’s technology as “interesting”, they are wary about how a dispute about the ownership of its parent company and major shareholder, United Biomedical, could affect Vaxxinity.
Vaxxinity's technology is licensed from United, which has employed it in animal vaccines. The dispute involves United’s founder, Chang Yi Wang, who is also the mother of Vaxxinity’s chief executive, Mei Mei Hu; there is significant overlap between the two companies’ boards.
However, Ms Hu tells Evaluate Vantage: “We've had many lawyers looking at it from both sides, and they're very confident that [the dispute] doesn't impair Vaxxinity’s ability to operate whatsoever.” A partner would typically want to see such a dispute settled before doing a deal.
A sheep in wolf’s clothing
These matters aside, Vaxxinity thinks it has solved a major problem that hit previous attempts to develop Alzheimer’s shots; namely, how to spur the body to produce antibodies against endogenous, or self, antigens.
“Most of the time, it's not going to respond because it doesn't want to attack itself,” says Ms Hu. Alzheimer’s vaccine developers have, therefore, tried to “rile up” the immune system, she says, “but the problem was they riled it up too much”.
This led to toxicity concerns. Ms Hu points to Elan and Wyeth’s AN-1792, which was discontinued in 2002 after being associated with meningoencephalitis.
Ms Hu reckons Vaxxinity has got the balance right, however. “The way I like to think about it is we put a sheep in wolf's clothing.” The “sheep” in the case of UB-311 is a short fragment of the amyloid-beta peptide. This is linked to the “wolf”, a TH peptide carrier, designed to activate T-helper cells and trigger an immune response.
However, Evercore noted that the sample size was likely too small to feel confident, and that the effect sizes would likely dwindle in larger trials.
Ms Hu, who spoke to Vantage after the recent success of Biogen and Eisai’s lecanemab, but before the failure of Roche's gantenerumab, thinks that there is renewed excitement around the amyloid hypothesis, which could help with Vaxxinity’s partnering discussions. “The whole industry has got some more wind in its sails.”
And gantenerumab’s setback will probably do little to dent the amyloid hypothesis, given the low levels of amyloid-beta clearance seen with that project.
The chasing pack
There are a couple more groups with projects in mid-stage studies that will hope to catch Vaxxinity. Grifols reported phase 2 immunogenicity data with its contender, ABvac40, at the AD/PD meeting in March, with exploratory efficacy endpoints still under analysis. No cases of Aria-E were seen here, either.
Grifols has taken an approach that differs from Vaxxinity's, with the immune response to ABvac40 being driven by a keyhole limpet cyanine carrier protein and the adjuvant alum hydroxide.
Meanwhile, by the end of this year AC Immune expects to report interim data from the phase 1/2 Abate study of its liposome vaccine candidate ACI-24.060 in prodromal Alzheimer’s patients, and make a decision on whether to move into Down syndrome-related Alzheimer’s.
Still, therapeutic vaccine candidates for various diseases have failed to live up to expectations. In Alzheimer's, there is the added risk that these developers are pursuing a hypothesis – around amyloid – that itself has many doubters.
Amyloid-beta vaccines in clinical development
Project
Company
Status
Phase 2
UB-311
Vaxxinity
Ph2a data in mild AD reported; seeking partner for ph2b
ABvac40
Grifols (Araclon subsidiary)
Data reported from part A of ph2 in MCI and very mild AD, part B (crossover) continues
ACI-24.060
AC Immune
Interim data from ph1/2 Abate in prodromal AD due YE 2022; US IND planned Q1 2023
Japan's Eisai Co plans to seek full approval of its experimental Alzheimer's drug lecanemab in the United States, Europe and Japan armed with data showing it can slow the brain-wasting disease for people with early symptoms, potentially getting the treatment to patients next year.
It remains unclear how widely the drug developed with U.S. biotech Biogen Inc will be used due to uncertainty over insurance coverage, including the U.S. government's Medicare plan for people age 65 and over, potential side effects and cost.
One Wall Street analyst said he is not counting on measurable sales until 2024. Several estimated lecanemab may be priced at around $20,000 per year.
"Most people who this (drug) would apply to are on Medicare, and most private payers look to Medicare as they make their own (coverage) decisions. So there's a massive roadblock in the way of all who could benefit from this treatment," said Robert Egge, Alzheimer's Association chief public policy officer
Eisai confirmed on Tuesday that lecanemab - an antibody designed to remove sticky deposits of a protein called amyloid beta from the brain - reduced the rate of cognitive decline on a clinical dementia scale by 27% compared to a placebo. It also gave new details on side effects including a dangerous type of brain swelling and brain bleeding.
The companies have already applied for accelerated approval with the U.S. Food and Drug Administration and expect a decision by Jan. 6. The new data will allow them to apply for full approval within days of that decision, Eisai's U.S. CEO Ivan Cheung said in an interview.
"The medication is only for people in the very early stages of Alzheimer's," said Dr. Babak Tousi, a neuro-geriatrician at the Cleveland Clinic. These are people with some memory impairment but who can still engage in daily activities such as manage finances and medications, prepare meals and drive. "This is a very, very small, selective group," he said.
Guggenheim Partners analyst Yatin Suneja said he expects the drug to get full U.S. approval in the second half of 2023, adding that Medicare would likely wait for formal approval before deciding on coverage terms.
Most U.S. Alzheimer's patients are insured through Medicare, which will only cover patients in clinical trials for anti-amyloid drugs that have received a less stringent accelerated approval, severely limiting access to such medicines. There are no such trials ongoing, Egge said.
Michael Irizarry, Eisai's deputy chief clinical officer, told Reuters ahead of the data release that the company has been in discussions with the agency about reconsidering its policy on Alzheimer's drug coverage.
It is unclear how long the U.S Centers for Medicare & Medicaid Services (CMS) might take to make such a coverage determination. Irizarry said a formal process between Eisai and CMS could not begin until after the drug is approved.
CMS did not provide an immediate comment.
RBC Capital Markets analyst Brian Abrahams said he expects limited sales revenue from lecanemab in 2024.
"CMS might wait for full approval of the drug in the back half of next year before potentially broadening (its policy) and enabling coverage of lecanemab," Abrahams said.
He estimated about 23,000 U.S. patients for the drug in the first year, rising to over 300,000 by 2031.
In a June study on lecanemab's worth, Eisai said based on mid-stage trial data indicating the drug's effectiveness, a price between $9,249 to $35,605 per year represented a good value. The drug is given by infusion every two weeks based on a patient's weight.
Elon Musk said on Wednesday he expects a wireless brain chip developed by his company Neuralink to begin human clinical trials in six months, after the company missed earlier timelines set by him.
The company is developing brain chip interfaces that it says could enable disabled patients to move and communicate again, with Musk adding on Wednesday that it will also target restoring vision.
Based in the San Francisco Bay Area and Austin, Texas, Neuralink has in recent years been conducting tests on animals as it seeks approval from the U.S. Food and Drug Administration (FDA) to begin clinical trials in people.
“We want to be extremely careful and certain that it will work well before putting a device into a human,” Musk said during a much-awaited public update on the device.
Speaking to a crowd of select invitees in a presentation at Neuralink headquarters that lasted nearly three hours, Musk emphasized the speed at which the company is developing its device.
Neuralink has conducted tests on animals to seek approval from the U.S. Food and Drug Administration (FDA) to begin clinical trials in people.NurPhoto via Getty Images
“The progress at first, particularly as it applies to humans, will seem perhaps agonizingly slow, but we are doing all of the things to bring it to scale in parallel,” he added. “So, in theory, progress should be exponential.”
The FDA did not immediately reply to Reuters’ request for comment.
The first two human applications targeted by the Neuralink device will be in restoring vision and enabling movement of muscles in people who cannot do so, Musk said. “Even if someone has never had vision, ever, like they were born blind, we believe we can still restore vision,” he said.
Musk said that he wants to be certain that it will work before putting the device into a human.AFP via Getty Images
The event was originally planned for Oct. 31 but Musk postponed it just days before without giving a reason.
Neuralink’s last public presentation, more than a year ago, involved a monkey with a brain chip that played a computer game by thinking alone.
Musk, who also runs electric vehicle manufacturer Tesla, rocket firm SpaceX, and social media platform Twitter, is known for lofty goals such as colonizing Mars and saving humanity. His ambitions for Neuralink, which he launched in 2016, are of the same grand scale.
He wants to develop a chip that would allow the brain to control complex electronic devices and eventually allow people with paralysis to regain motor function and treat brain diseases such as Parkinson’s, dementia and Alzheimer’s. He also talks of melding the brain with artificial intelligence.
Neuralink, however, is running behind schedule. Musk said in a 2019 presentation he was aiming to receive regulatory approval by the end of 2020. He then said at a conference in late 2021 that he hoped to start human trials this year.
Neuralink has repeatedly missed internal deadlines to gain FDA approval to start human trials, current and former employees have said. Musk approached competitor Synchron earlier this year about a potential investment after he expressed frustration to Neuralink employees about their slow progress, Reuters reported in August.
Synchron crossed a major milestone in July by implanting its device in a patient in the United States for the first time. It received U.S. regulatory clearance for human trials in 2021 and has completed studies in four people in Australia.
Eli Lilly and Company(NYSE: LLY) has announced that donanemab met all primary and secondary endpoints for the 6-month primary outcome analysis in the Phase 3 TRAILBLAZER-ALZ 4 study, providing the first active comparator data on amyloid plaque clearance in patients with early symptomatic Alzheimer's disease treated with amyloid-targeting therapies. These data comparing donanemab to Aduhelm® * (aducanumab-avwa) to assess superiority on amyloid plaque reduction were shared at the 15th Clinical Trials on Alzheimer's Disease (CTAD) conference. Donanemab is an investigational antibody that targets a modified form of beta amyloid plaque called N3pG.
Through the FDA's accelerated approval pathway, the FDA has recognized that the reduction of amyloid beta plaque is a biomarker reasonably likely to predict clinical benefit in the treatment of early Alzheimer's disease.
"The purpose of this first ever active comparator trial of amyloid lowering agents was to answer important questions about potential differences in amyloid plaque reduction," said Mark Mintun, M.D., group vice president of pain and neurodegeneration research and development, Eli Lilly and Company. "These data reinforce our confidence in donanemab's unique mechanism of action based on reductions in key biomarkers of Alzheimer's disease, amyloid plaque and plasma phosphorylated tau (P-tau). Importantly, this was also the first study to obtain ARIA rates side by side using identical methods for ARIA assessment in the same patient population, demonstrating the ability to disconnect rate of plaque clearance from rate of ARIA incidence."
In the co-primary outcomes, brain amyloid plaque clearance, defined as achieving brain amyloid plaque levels of <24.1 Centiloids, was achieved in 37.9% of donanemab-treated participants (25 of 66) compared with 1.6% of Aduhelm-treated patients (1 of 64) at 6 months; in the intermediate tau subpopulation, 38.5% of donanemab-treated participants (10 of 26) reached brain amyloid clearance compared with 3.8% of Aduhelm-treated participants (1 of 26) by 6 months. In a key secondary outcome, donanemab reduced brain amyloid levels vs. baseline by 65.2% compared with 17.0% for Aduhelm at 6 months. In an exploratory outcome, donanemab, but not aducanumab-avwa, treatment significantly reduced plasma P-tau217 at 6 months compared to baseline.
The safety profile of both treatments was consistent with their previously published studies. ARIA was the most common treatment emergent adverse event in both groups. In the aducanumab-avwa group, the incidence of total ARIA was 26.1% with 4.3% being symptomatic. In the donanemab group, the incidence of total ARIA was 25.4% with 2.8% being symptomatic. For both treatments, all symptomatic cases were related to ARIA-E.
"It is encouraging to see that donanemab produced significant reduction of amyloid build up in the brain and P-tau in the blood after 6 months. This suggests that this treatment modified the biology of Alzheimer's disease early on in treatment," said Stephen Salloway, MD, associate director of the Center for Alzheimer'sDisease Research at Brown University, who presented the findings. "It is also notable in TRAILBLAZER-ALZ 4 that the higher amyloid clearance by donanemab compared to aducanumab-avwa at 6 months was not associated with a higher rate of ARIA."
TRAILBLAZER-ALZ 4 is ongoing and will have 12-month and 18-month secondary analyses. The study is one of five studies that comprise the clinical program to evaluate the efficacy and safety of donanemab. In August, Lillyannounced that the FDA accepted the donanemab application for review, with Priority Review designation, for Alzheimer's disease under the accelerated approval pathway.
Immigration and Customs Enforcement (ICE) accidentally posted a document online Monday containing personal information of more than 6,000 noncitizens seeking protection, the agency announced.
ICE said in a statement on Wednesday that the document was posted on its website for about five hours while the agency was performing routine updates and it took “swift action” to fix the mistake once it was notified. The Excel spreadsheet included 6,252 immigrants’ names, immigration information and other personally identifiable information.
“Though unintentional, this release of information is a breach of policy and the agency is investigating the incident and taking all corrective actions necessary,” ICE said.
The Los Angeles Times first reported ICE’s inadvertent disclosure.
The nonprofit Human Rights First, which advocates for the United States to protect human rights, first notified ICE of the information, and it was taken down about 10 minutes later.
ICE said it is notifying those impacted or their attorneys of the disclosure, which will allow them to determine if it will impact their claim for receiving protection from the U.S. government. The agency notified the Department of Homeland Security’s chief privacy officer and other oversight bodies and is monitoring the internet for any reposting of the document.
It also placed alerts on all people whose information was made public to ensure that the agency does not take further action on their claim before determining if the disclosure affects it.
ICE plans to identify any entity that accessed the information through their IP addresses and will send them a letter requesting that they destroy the document.
