In the midst of a devastating mental health crisis affecting thousands of American teens, Northeastern University psychology professor Susan Whitfield-Gabrieli says a non-invasive remedy for depression and anxiety offers hope.
In a brain imaging study conducted at Northeastern's Biomedical Imaging Center, teenagers using mindfulnessmeditationguided by neurofeedback were able to calm a network of regions of the brain associated with depression, anxiety, ADHD and other disorders.
At the same time that region, known as the default mode network (DMN) grew less active, the central executive network (CEN) associated with goal-setting, problem-solving and sustained attention increased in function.
"Mindfulness helps with anxiety and depression," says Whitfield-Gabrieli, whose research was published Wednesday in Molecular Psychiatry.
The study of nine people ages 17 to 19 is "proof of concept" that young people can be trained in mindfulness meditation—and that it produces results, she says.
Larger scale studies need to be done showing the efficacy of mindfulness meditation in teens and younger students, but Whitfield-Gabrieli says she and her collaborators at Massachusetts General Hospital and Columbia University are optimistic about the results from Northeastern.
So far, other therapeutic remedies for depression and anxiety, including medical and talk therapy, have a success rate of approximately 30% to 50%, Whitfield-Gabrieli says.
She says that's not nearly enough to deal with an epidemic of adolescent mental health disorders. "We need personalized interventions that target the brain networks known to be associated with clinical symptoms," Whitfield-Gabrieli says.
A report released in February by the Centers for Disease Control and Prevention says teen girls were experiencing record rates of sadness and more than 40% of high school survey respondents said they had felt so sad or hopeless that they could not engage in their regular activities for at least two weeks during the previous year.
"We need to catch these kids before they fall," Whitfield-Gabrieli says. "Why not have mindfulness meditation as part of the school curriculum?"
The neurofeedback didn't involve electrodes but had students lie in functional magnetic resonance imaging scanners that focused on specific regions of their brains.
The default mode network regions associated with depression and anxiety are activated when people worry about the future and hash over the past, Whitfield-Gabrieli says, adding that she calls engaging this area of the brain "mental time travel."
When the default mode network regions are activated, the central executive network regions associated with the ability to manage tasks and regulate moods show less activity, Whitfield-Gabrieli says.
The activity in the different areas of the brain rises and falls in a type of dance or synchrony that is more pronounced the more psychopathology is present, she says.
The goal of the researchers was to use fMRI signals to moderate the activity, and it worked, Whitfield-Gabrieli says.
"As soon as the person starts doing the mindfulness meditation, the DMN drops," she says.
To make the exercise even more engaging for the teens, the researchers converted it into a game.
When the participant got the DMN to reduce activity, they'd get a signal to move a ball up towards a target circle. But if that region of the brain started getting more active, the ball would drop.
"They are literally just moving the ball with their mind. They love it," Whitfield-Gabrieli says.
"Mindfulness meditation forces you to attend to the present moment. You are no longer caught in the past or the future," she says.
There's no reason not to incorporate mindfulness meditation and guided breathwork into school curricula now, Whitfield-Gabrieli says.
She says eventually she would like to see neurofeedback work with other biomarkers such as heart rate to develop interventions for when people fall into vulnerable states of repetitive negative thinking.
In the near future, a smart phone might be able to pick up on the signals and request the user to "do mindfulness meditation now," exercise or remember to take an antidepressant, she says.
"People are realizing more and more the amazing effective and global impact mindfulness meditation can have."
More information: Jiahe Zhang et al, Reducing default mode network connectivity with mindfulness-based fMRI neurofeedback: a pilot study among adolescents with affective disorder history, Molecular Psychiatry (2023). DOI: 10.1038/s41380-023-02032-z
An analysis of human brain cells provides new evidence in support of the "amyloid hypothesis," the prevailing idea that Alzheimer's is caused by the accumulation of beta-amyloid proteins in the brain.
In the study, Columbia University researchers found thatamyloidsparks an alliance between two proteins in the brain's neurons and this pairing is linked to about half of the gene changes that are known to occur in the disease, triggering the rapid accumulation of tau proteins, a primary driver of neurodegeneration in the disease.
"This protein pair seems very central to the disease, and because it does not appear to have another function in the brain, it is a good target for a new therapy," says the study's senior author, Ulrich Hengst, Ph.D., associate professor of pathology & cell biology (in the Taub Institute for Research on Alzheimer's Disease and the Aging Brain) at the Columbia University Vagelos College of Physicians and Surgeons.
Protein pair was hidden to previous research
The researchers found the pair when they were looking for proteins that spark hundreds of changes in gene activity that occur in brain cells during Alzheimer's disease. "Our thought was that if we can interfere with the proteins and prevent those changes, we can prevent the disease," says Cláudio Gouveia Roque, Ph.D., associate research scientist in the Hengst lab, who conducted the study.
Instead of looking for proteins that act alone, the researchers looked for pairs of different proteins working together.
"We know this type of protein necessarily works in pairs, but previous Alzheimer's research hadn't looked for specific pairs. Consequently, our understanding of the changes underlying Alzheimer's progression has been fragmented and incomplete," says Hengst. "And because of that, we've most likely missed therapeutic opportunities."
Amyloid causes proteins to stick together
The search by Hengst and Gouveia Roque, together with a previous associate research scientist in the Hengst lab, Jimena Baleriola, uncovered two proteins—ATF4 and CREB3L2—whose binding to each other is triggered by amyloid and that together interact with about 50% of the gene expression changes that occur in brain cells during Alzheimer's disease.
Once formed, the CREB3L2-ATF4 pair activates a network of other proteins that cause deadly tau deposits to accumulate inside neurons. The protein pair also disables the cellular machinery that clears old and damaging proteins from neurons, another hallmark of Alzheimer's.
Although CREB3L2 and ATF4 are also found alone in healthy neurons, their binding together is greatly increased in the presence of a stress like excess amyloid, the researchers found.
"These two proteins are like two teenage boys," says Hengst. "Individually, they may be relatively harmless. But if you put them together without a responsible adult in the room, they're likely to be up to no good."
New treatment approach
The findings suggest that Alzheimer's could be treated by interfering with the CREB3L2-ATF4 pair.
"Normally, proteins that control gene activity are very poor drug targets because they control too many genes. But by targeting this pair we might be able to preserve the function of the two individual proteins while preventing the bad effects of them binding together," Hengst says.
Hengst and Gouveia Roque have already identified a drug, dovitinib, that interferes with the effects of the protein pair. Dovitinib has been approved by the FDA for the treatment of renal cancer but has not been tested for the treatment of Alzheimer's. "Nonetheless, the drug is not toxic to neurons and crosses the blood-brain barrier, so this bodes well for future drug development," Hengst says.
"We're not talking about getting rid of amyloid with this approach," adds Gouveia Roque. "If we can interfere with the protein pair, we could slow or perhaps even stop the progression of the disease. Yes, there would still be amyloid in the brain, but the neurons would react far less to it. One could hypothesize that such a drug could be used in combination with an amyloid-reducing drug for even greater effect."
The paper is published in the journal Science Advances.
More information: Cláudio Gouveia Roque et al, CREB3L2-ATF4 heterodimerization defines a transcriptional hub of Alzheimer's disease gene expression linked to neuropathology, Science Advances (2023). DOI: 10.1126/sciadv.add2671
There are approximately 30 trillion cells in a human body and our health is predicated on them properly interacting with and supporting each other, with the immune system playing a particularly pivotal role. One of the defining characteristics of aging is a decline in the proper functioning of our immune system. Centenarians, a rare population of individuals who reach 100 years or more, experience delays in aging-related diseases and mortality which suggests their immune systems remain functional into extreme old age.
Led by researchers from Boston University Chobanian & Avedisian School of Medicine and Tufts Medical Center, a new study findscentenariansharbor distinct immune cell type composition and activity and possess highly functional immune systems that have successfully adapted to a history of sickness allowing for exceptional longevity. Theseimmune cellsmay help identify important mechanisms to recover from disease and promote longevity.
"Our data support the hypothesis that centenarians have protective factors that enable to recover from disease and reach extreme old ages," said lead author Tanya Karagiannis, Ph.D., senior bioinformatician, Center for Quantitative Methods and Data Science, Institute for Clinical Research and Health Policy Studies at Tufts Medical Center.
"We assembled and analyzed what is, to our knowledge, the largest single-cell dataset of centenarian subjects that allowed us to define unique features of this population that support the identification of molecular and lifestyle factors contributing to their longevity," explained senior author Stefano Monti, Ph.D., associate professor of medicine at the School of Medicine.
To identify immune-specific patterns of aging and extreme human longevity, the researchers performed single cell sequencing on peripheral blood mononuclear cells (PBMCs)—a broad category of immune cells circulating in the blood—taken from seven centenarians enrolled in the New England Centenarian Study, one of the largest studies of long-lived individuals in North America led by Thomas Perls, MD, at the School of Medicine.
They then integrated this dataset with two publicly available single‐cell RNA sequencing (scRNA-seq) datasets of PBMCs to investigate compositional and transcriptional changes in circulating immune profiles across the human lifespan and extreme old age.
Lastly, they applied advanced computational techniques to analyze the combined data, to evaluate how the cell type composition (the proportion of different cell types) and activity change as a function of age, and whether centenarians manifest profiles capturing or escaping the expected age progression.
Their analysis confirms observations made in previous studies of aging and identifies novel cell type-specific compositional and transcriptional changes that are unique to centenarians and reflect normal immune response.
According to the researchers, when people are exposed to infections and recover from them, their immune system learns to adapt, but this ability to respond declines as we age.
"The immune profiles that we observed in the centenarians confirms a long history of exposure to infections and capacity to recover from them and provide support to the hypothesis that centenarians are enriched for protective factors that increase their ability to recover from infections," said senior author Paola Sebastiani, Ph.D., director, Center for Quantitative Methods and Data Science, Institute for Clinical Research and Health Policy Studies at Tufts Medical Center.
The researchers believe these findings provide a foundation to investigate mechanisms of immune resilience likely contributing to extreme longevity as a target for healthy aging therapeutics. "Centenarians, and their exceptional longevity, provide a 'blueprint' for how we might live more productive, healthful lives. We hope to continue to learn everything we can about resilience against disease and the extension of one's health span," said senior author George J. Murphy, Ph.D., associate professor of medicine at the School of Medicine.
These findings appear online in eBiomedicine.
More information: Tanya T. Karagiannis et al, Multi-modal profiling of peripheral blood cells across the human lifespan reveals distinct immune cell signatures of aging and longevity, eBioMedicine (2023). DOI: 10.1016/j.ebiom.2023.104514
A drug approved in 2019 for macular degeneration apparently caused rare retinal side effects because of its interactions with the human immune system, two new studies have concluded.
The drug, a monoclonal antibody called brolucizumab, was developed by Swiss pharmaceutical giant Novartis AG for an eye condition known as wet age-relatedmacular degeneration, or simply, AMD. The disorder is a leading cause of vision loss in people 65 and older. AMD not only causes severe blurring, it is characterized by a blind spot in the center of the retina, the macula of the eye. The disorder is characterized by an overgrowth of abnormal blood vessels that leak into the macula. Brolucizumab was developed to specifically target the damaging overgrowth.
The medication is approved in more than 70 countries, but while it was deemed safe in pre-approval testing, reports emerged a few months after its launch noting rare retinal disorders in a small percentage of patients treated with the drug. These side effects impacted an estimated 2.1% of patients, according to data in the journal Science Translational Medicine.
Scientists at two Novartis research centers embarked on investigations to determine what went awry. These probes were undertaken at the Novartis Institutes for Biomedical Research in Basel, Switzerland, and Cambridge, Massachusetts.
Scientists in one study examined serum samples, and in the other, created models of the inflammatory conditions patients experienced. The single aim of the research on two continents was to address the mystery underlying why this medication became linked to retinal side effects in some patients while the majority of patients treated with the drug were problem-free.
"In October 2019, Novartis launched brolucizumab, a single-chain variable fragment molecule targeting vascular endothelial growth factor A, for the treatment of neovascular age-related macular degeneration," wrote Anette C. Karle of the company's biomedical research division in Basel.
Vascular endothelial growth factor-A (VEGF-A) is a signaling protein with multiple activities, one of which is prompting the growth of aberrant blood vessels. Wet AMD is caused by abnormal blood vessels growing in the layer of the eye called the choroid, situated underneath the light-sensitive retina. Blood vessel overgrowth leads to vision loss in AMD.
Writing in the Science Translational Medicine, Karle noted that patients who didn't fare well on the drug developed telltale conditions of the eye. "In 2020, rare cases of retinal vasculitis and/or retinal vascular occlusion were reported, often during the first few months after treatment initiation, consistent with a possible immunologic pathobiology," Karle, lead author of one of the new studies noted.
Retinal vasculitis is an inflammatory condition affecting blood vessels of the retina, the light-sensitive tissue at the rear of the eye. The most insidious aspect of retinal vasculitis is the painless loss of vision. Retinal vascular occlusion, on the other hand, is caused by a blockage in veins moving blood away from the retina. The blockage can lead to edema—fluid retention—in the macula. This trapped fluid accumulates not only within the retina but under it, leading to rapid and severe loss of visual acuity.
According to the research by Karle and colleagues, retinal disorders were "inconsistent with preclinical studies in cynomolgus monkeys that demonstrated no drug-related intraocular inflammation, retinal vasculitis or retinal occlusion, despite the presence of preexisting and treatment-emergent antidrug antibodies in some [test] animals." However, a small number of patients in the clinical trial experienced the two inflammatory conditions after treatment with brolucizumab.
To understand why the medication didn't work for some patients, Karle and her collaborators compared serum samples from select groups: nonhuman primates, untreated healthy volunteers, and 28 patients from the clinical trials who experienced retinal vasculitis or retinal vascular occlusion after brolucizumab treatment.
Serum analyses revealed that an immune response against brolucizumab was a prerequisite for both side effects because only patients with retinal vasculitis or retinal vascular occlusion showed strong T cell responses to the treatment. Patients' immune systems were attacking their retinas after treatment with the drug.
In a second study, also reported in Science Translational Medicine, Dr. Jeffrey Kearns and colleagues adopted a translational approach to elucidate how the body can unleash inflammatory forces after treatment with brolucizumab.
Kearns' team, based in Cambridge, Massachusetts, and Basel, Switzerland, integrated structural modeling, immunological analysis, and other techniques to investigate the root causes of retinal vasculitis and retinal vascular occlusion.
"The presence of antidrug antibodies in these patients led to the initial hypothesis that immune complexes could be key mediators," wrote Kearns, a researcher at the Novartis Institutes for BioMedical Research in Cambridge, and lead author of the second study. "Although the formation of antidrug antibodies and immune complexes may be a prerequisite, other factors likely contribute to some patients having retinal vasculitis or retinal vascular occlusion, whereas the vast majority do not."
Kearns and his collaborators studied brolucizumab's effects in a systems pharmacology model that mimicked conditions in the eye. Using the model allowed researchers to identify several factors that drove the treatment's interactions with immune cells.
These factors included a linear epitope on the drug shared with gut bacterial proteins, and the appearance of non-native derivatives of brolucizumab after 13 weeks. These manifestations led to the formation of immune complexes between brolucizumab and anti-drug antibodies.
Karle and Kearns, along with their colleagues, caution that more work is needed for more definitive answers. Both researchers note that other unknown factors could be at play, as their experiments were limited by a dearth of intraocular clinical samples and a lack of genetic risk factors.
More information: Anette C. Karle et al, Anti-brolucizumab immune response as one prerequisite for rare retinal vasculitis/retinal vascular occlusion adverse events, Science Translational Medicine (2023). DOI: 10.1126/scitranslmed.abq5241
Jeffrey D. Kearns et al, A root cause analysis to identify the mechanistic drivers of immunogenicity against the anti-VEGF biotherapeutic brolucizumab, Science Translational Medicine (2023). DOI: 10.1126/scitranslmed.abq5068
Any federal department head with a $60.4 billion annual spending request is going to see fiscal hawks on Congressional panels flash their budget-cutting knives in appropriations hearings.
But when it comes to embattled United States Department of Homeland Security (DHS) Secretary Alejandro Mayorkas—literally, the face of President Joe Biden’s much-maligned border and immigration policies—House Republicans don’t want to trim his budget, they want his head on a platter.
According to DHS, there have been 4.7 million “encounters” with illegal immigrants reported at the nation’s southern border since the Biden administration assumed office in January 2021.
Secretary of Homeland Security Alejandro Mayorkas testifies before the Senate Homeland Security and Governmental Affairs Committee in Washington on March 28, 2023. (Kevin Dietsch/Getty Images)
An estimated 1.3 million “got-aways” have eluded border agents and escaped into the country—a figure many say is underestimated by up to 20 percent.
As a result critics, which include the entire Republican Congressional contingent as well as some Democrats, say there were more than 1,100 attacks on U.S. Border Patrol and Customs and Border Protection (CBP) agents while the flow of fentanyl remains unabated across the southern border, contributing to more than 75,000 poisoning deaths attributed to the drug in 2022.
“Mr. Secretary, you are failing at doing your job. These numbers speak for themselves,” Rep. Ashley Hinson (R-Iowa) said.
“The policies of this administration have directly contributed to this failure. In my mind, it is very clear this has been a complete failure in you doing your job and we need new leadership.
“What will it take for you to resign and step down from this … because I see this as a complete failure. What will it take?” Hinson asked.
Mayorkas didn’t directly respond to Hinson’s query during his two-and-a-half-hour March 29 hearing before the House Appropriation Committee’s Homeland Security Subcommittee.
Nor did the DHS chief answer pointed questions about allegedly shifting funding away from already allocated money for border wall construction, or respond to queries about whether Mexican cartels should be declared foreign terrorist organizations or his claim in April 2022 that DHS had “operational control” of the border. That statement was later refuted by U.S. Border Patrol Chief Raul Ortiz.
It was Mayorkas’s second Congressional hearing of the week and the first of two set for March 29.
The day before, he was ripped by Senate Appropriations Committee Republicans with Texas Sens. John Cornyn and Ted Cruz calling for him to “be fired” or, as a bill now circulating about Capitol Hill demands, be impeached.
“For over two years, we’ve seen skyrocketing illegal migration at the border. This policy-driven crisis continues for one reason, and one reason only, this administration is unwilling to publicly dissuade migrants from coming to the border and unwilling to take action on the authority it already has on the books,” Subcommittee Chair Rep. Dave Joyce (R-Ohio) said.
“The Biden administration’s policies are undoubtedly driving our border security crisis,” he continued and referring to the DHS’s $60.4 billion Fiscal Year 2024 (FY24) budget request added, “It is our job as appropriators to be good stewards of taxpayers’ money and to ensure we are not wasting money by supporting bad policies that don’t result in deserted outcomes.”
Budget of Wasteful ‘Gimmicks’
DHS’s FY24 budget request actually tops $103 billion with $60.4 billion defined as “discretionary.”
The department’s 260,000 employees deal with a wide range of domestic security concerns addressed by the Transportation Security Agency, the Coast Guard, FEMA, and the Secret Service.
“This proposal is, unfortunately, more disappointing than it is promising,” Joyce said. “The budget is full of gimmicks that mask the true cost of protecting the homeland and makes our job as appropriators that much more difficult.”
The department’s total $60.4 billion budget request is “nearly equal to the current fiscal year,” he said but cited the $4.7 billion for the proposed Southwest Border Contingency Fund and another $1.6 billion in “illegal TSA fees” as wasteful allocations that will cost taxpayers more than $6 billion without addressing border security.
“Now is not the time for budget gimmicks,” Joyce said.
Demurrals On The Wall
Republicans called the Southwest Border Contingency Fund a “slush fund” with Joyce claiming it “will spend more hard-earned tax dollars to achieve the same results with less oversight … that incentivizes this administration to not solve problems and do their job in the first place.”
The Biden administration is more dedicated to building more infrastructure for processing illegal immigrants “and then releasing them into the interior, [which] hasn’t worked,” Joyce said.
“Decreasing detention capacity hasn’t worked. Border security operators have been clear—without [increasing detention capacities] illegal immigration will continue unabated.”
Rep. Michael Cloud (R-Texas) said the $4.7 billion fund is “disturbing” because it essentially concedes the border cannot be safeguarded.
“What has happened under this administration is instead of trying to stop the flow of illegal immigrants across the border, we’ve just gotten better at processing those immigrants,” he said.
Cloud, House Appropriations Committee Chair Rep. Kay Granger (R-Texas), and Rep. Michael Guest (R-Miss.) accused Mayorkas of funneling money from revenue streams dedicated to building the border wall established under the Trump administration to other programs and projects.
Granger said there is $2.8 billion set aside to “complete the wall” with $200 million of that set to “go away” unless it is spent “in the next few months.”
“We just going to let that happen?” she asked.
Mayorkas would not answer the question but said he has approved 129 “gates and gaps” projects along stretches of the wall that already exist.
Illegal immigrants, mostly of Venezuelan origin, attempt to forcibly cross into the United States at the Paso del Norte International Bridge in Ciudad Juarez, Chihuahua state, Mexico, on March 12, 2023. (Herika Martinez/AFP via Getty Images)
The Biden administration is not going to approve any more wall construction, he said, and is espousing technologies, such as drones, and “investing in personnel.”
“I have approved a number of projects and we will comply with our legal obligations with respect to the funds provided for the wall,” Mayorkas said.
Cloud said DHS prevented Texas from funding portions of the wall on its own. “Right now,” he asked, “we’re paying for [the] border wall to be stored and not built. Is that correct?
“We are indeed,” Mayorkas said.
Cloud said Border Patrol and CPB officials themselves say, “the border wall is the most effective force-multiplier” claiming the budget request “takes money we’ve already allocated and moves it in different directions, is that correct?”
“We will comply with our legal obligations,” Mayorkas said.
“It’s not people or infrastructure. It’s both,” Cloud said. “You are taking what we already appropriated for border wall construction and rescinded that and want to use that for other purposes. Is that correct?”
“Congressman,” Mayorkas replied, “we will comply with our legal obligations.”
“That’s a well-worded way to get around” answering the question, Cloud said. “You’re missing the overall objective of securing the border by funding these little legal loopholes to get out of things.”
“I understand we are not going to build a wall from sea to shiny sea,” Guest said, but a wall is effective in certain places in certain sectors.
“It seems to me this administration is saying we are not going to build any walls. Walls are bad. I disagree with that, walls are beneficial. I think that they do a great job.”
Fire ‘Border Czar’ Too
Hinson said the Border Patrol is budgeted for 19,800 agents but now has only about 19,000. She said Ortiz maintains it needs at least 22,000 agents to effectively patrol the border.
She said DHS should be asking for many more agents, which is an initiative his GOP critics would support.
Mayorkas said the Border Patrol added 300 agents last year and will continue to build its ranks every year. “There is a limit to how many we can functionally hire in a particular year.”
He said, “We need more.”
Good luck, Hinson said. “The policies of this administration have truly affected retention” and said the budget reflects “a lack of meaningful work to address retention challenges. Throwing out increased numbers looks nice, but it doesn’t actually address the reality of the situation at the southern border.”
Rep. Andy Harris (R-Md.) suggested if the administration needs more money to hire Border Patrol agents, he has some ideas.
“It’s strange that this department wants to add 350 Border Patrol agents and 87,000 armed IRS agents,” he said, suggesting Mayorkas contact the IRS “and see if it wants to share some of that wealth with you and perhaps share some of the funding with you.”
Harris said Mayorkas should not be the only administration official to resign over the border situation. Vice President Kamala Harris, as the designated “border czar,” should also step down, he said.
“The last time she was [at the border] was June 2021, that’s more than 2 million crossings ago,” he said. “Our border czar should also resign because she isn’t doing her job.”
A large, international survey of thousands of doctors has revealed that a majority are still not confident enough to prescribe digital therapeutics(DTx) to their patients.
The finding has emerged from Ipsos’ latest two-yearly Digital Doctor Survey, which showed that only 19% of almost 3,500 doctors polled across 20 countries had prescribed a DTx to their patients, while just 25% had recommended one.
Almost two-thirds (62%) felt there is not enough training on how to use digital health interventions, but sizeable proportions of respondents also felt there was either a lack of efficacy (48%) or a lack of evidence for their efficacy (46%).
Ipsos said that the results show there is a need to address barriers surrounding emerging technologies such as DTx, as well as artificial intelligence (AI), although it noted there was much more enthusiasm for the latter.
All told, 69% of physicians were excited about the future role of AI in healthcare, although a minority (31%) had used AI in their practice in the last year and only 35% felt knowledgeable about the technology. The main benefits of AI cited by the doctors were the automation of repetitive tasks, and improving the efficiency and accuracy of diagnosis.
Among the other findings in the survey was a high level of agreement that connected health devices providing real-time health data will help patients manage their health more effectively and reduce strain on healthcare systems, a view supported by four out of five respondents.
That was accompanied, however, by concerns among around half of all doctors that patients could end up misinterpreting data or arrive at a diagnosis without physician supervision.
There are some marked differences in the latest poll compared to Ipsos’ prior one conducted in 2021, when the world was still firmly in the grip of the COVID-19 pandemic, including a reduction in the use of telehealth from a level of around 70% to 41%, which Ipsos suggests is the “new normal” and still higher than was seen in its pre-pandemic polls.
There was also broad agreement that remote consultations could have a benefit on improving access to healthcare overall, limiting the environmental footprint of the sector, and increasing patient diversity by recruitment from a wider pool as a benefit of decentralised clinical trials.
“We have been running Digital Doctor since 2015 and it is exciting to see the dial move from the perceived possibility of the benefit of technology in health to, now, a reality!” said Ipsos’ head of digital and connected health, Reena Sooch.
“Doctors want to use technology in their day-to-day practice, virtual care is happening at scale, and there is so much potential for AI and digital therapeutics if we get the infrastructure and reimbursement approaches right,” she added.
Chinese biotech Hutchmed has completed its rolling marketing application in the US for oral VEGF receptor inhibitor fruquintinib, which was licensed by Takeda for a hefty $400 million upfront in January.
The filing is for the treatment of refractory metastatic colorectal cancer (CRC), based on the results of the international FRESCO-2 study, which showed that treatment with fruquintinib reduced the risk of death by 34%.
The FDA granted fruquintinib a fast-track designation in metastatic CRC in 2020 on the back of the earlier FRESCO study, which also showed a 35% reduction in mortality in an equivalent refractory CRC population in China.
Applications for the VEGFR-1, -2, and -3 inhibitor – which is already sold in China under the Elunate brand name, in a partnership with Eli Lilly – are also being planned for Europe and Japan later this year. Takeda snapped up all rights to the drug outside China in a deal that could be worth a total of $1.13 billion.
There’s no shortage of drugs targeting VEGF on the market, but Hutchmed has designed fruquintinib as a new-generation compound with improved kinase selectivity intended to minimise off-target toxicities, improving tolerability and providing more consistent inhibition of VEGF.
That profile could make fruquintinib more suitable for use as part of combination therapies, according to the biotech, which is also developing the drug for advanced gastric cancer or gastroesophageal junction adenocarcinoma, breast cancer, and other solid tumours.
The market for VEGF therapies in CRC is also less competitive, with just three approved therapies, namely Roche’s Avastin (bevacizumab) and biosimilars, Lilly’s Cyramza (ramucirumab), and finally Bayer’s Stivarga (regorafenib), which will be its closest competitor in the refractory CRC space, along with Taiho’s chemotherapy drug Lonsurf (tipiracil hydrochloride and trifluridine).
CRC is the third most prevalent cancer worldwide, leading to around 935,000 deaths a year, according to 2020 data. In the US alone, an estimated 153,000 patients are diagnosed with CRC annually, with around 53,000 deaths.
If approved, fruquintinib looks set to be Hutchmed’s first product launch in the US, coming after an attempt to file another cancer candidate – surufatinib, for pancreatic and extra-pancreatic neuroendocrine tumours (NETs) – was shot down by the FDA last year on the grounds that the application was based on data generated almost entirely in China.
Last year, Hutchmed said it would have to prioritise getting approvals for its late-stage pipeline candidates to speed up its move to becoming a sustainably profitable business, reducing the number of drug programmes in development and launching a hunt for partners to take its candidates to market outside China.
Takeda’s buy-in – and the development and marketing muscle that it will apply to fruquintinib in CRC and follow-up indications – was a big step forward in helping it to meet that objective.
