Cytokinetics(CYTK) stock slumped Monday despite seemingly positive test results for itsBristol Myers Squibb(BMY)-rivaling treatment for a heart disease.
The company tested its drug, aficamten, in patients with obstructive hypertrophic cardiomyopathy, or HCM. In this condition, a genetic mutation causes the heart ventricles to thicken. This makes it difficult for the heart to pump blood — causing shortness of breath, chest pain and fainting during exercise.
After 24 weeks, patients who received aficamten had a significantly improved exercise capacity vs. the placebo group. Patients also showed improvements in 10 secondary goals of the study.
Cytokinetics Chief Executive Robert Blum called the results of the Sequoia study "pristine."
"The consistency and the robustness of these results, we think, are very compelling," he told Investor's Business Daily. "Having been involved in this business for a long time, I can't remember another occasion where I've been able to be associated with such a pristine data set across every one of the endpoints. That's a very rare privilege."
Shares initially rocketed 82.5% on Dec. 27 when Cytokinetics announced the top-line results of the Sequoia study. On Jan. 8, Cytokinetics shares jumped another 15% to a record high at 110.25 on takeover rumors. But the biotech stock has since pulled back almost 44% from that point.
Aficamten works by blocking an enzyme called myosin, helping reduce excessive heart contractility. It uses the same mechanism as Bristol Myers' Camzyos. But, Blum says, aficamten could be a safer version than Camzyos.
After 24 weeks, patients who received aficamten in the Sequoia study had a seven-point improvement in symptoms on the 100-point Kansas City Cardiomyopathy Questionnaire. The questionnaire assesses a patient's quality of life. On another measurement of heart failure symptoms, 34% of aficamten recipients improved by at least one class. There are four classes of heart failure.
Further, patients who received aficamten spent 78 fewer days eligible for septal reduction therapy, or SRT. Doctors recommend SRT for patients with hypertrophic cardiomyopathy when a medicine fails to control heart-failure symptoms. The aficamten treatment group also had an 80% reduction in a biomarker of cardiac wall stress compared with the placebo group.
Cytokinetics is now planning to ask the Food and Drug Administration and the European Medicines Agency to approve aficamten in the third and fourth quarters, respectively. The company is aiming for a mid-2025 launch.
In adults hospitalized with suspected sepsis, piperacillin-tazobactam was associated with a higher mortality rate and increased duration in organ dysfunction compared with cefepime, according to a retrospective cohort study.
In an instrumental variable analysis, empirical treatment with vancomycin and piperacillin-tazobactam resulted in a 5% absolute increase in 90-day mortality compared with empirical treatment with vancomycin and cefepime (22.5% vs 17.5%, P=0.002), Rishi Chanderraj, MD, MSc, of the Ann Arbor Veterans Affairs Hospital in Michigan, and colleagues reported.
In addition, piperacillin-tazobactam was also associated with 2.1 (95% CI 1.4-2.7) fewer organ failure-free days, 1.1 (95% CI 0.57-1.62) fewer ventilator-free days, and 1.5 (95% CI 1.01-2.01) fewer vasopressor-free days when compared with cefepime, the findings in JAMA Internal Medicineopens in a new tab or window showed.
"When it comes to early treatment in sepsis, all broad-spectrum antibiotics are not created equal," Chanderraj told MedPage Today. "Unless the patient has a specific indication for anti-anaerobic antibiotics, physicians should think carefully before using them and exposing their patients to unnecessary harm."
"A 2% to 5% mortality difference may not initially sound like much, but given how common and deadly sepsis is, the routine use of anti-anaerobic antibiotics in sepsis may lead to thousands of deaths per year," he added.
More than 65% of patients with sepsis receive broad-spectrum antibiotics targeting methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa, the authors pointed out. The combination of vancomycin and piperacillin-tazobactam is the most frequently prescribed empirical regimen for sepsis. Given the results of their study, the combination may contribute to one additional death per every 20 patients with sepsis, the authors wrote.
In a secondary analysis, the researchers looked at the association between receipt of any anti-anaerobic antibiotic and patient outcomes when compared with no receipt of anti-anaerobic antibiotics. Anti-anaerobic antibiotic treatment was associated with a 12% increase in 90-day mortality using a two-stage regression model (95% CI 3-21, P <0.001) and with a 14% increase in mortality using a non-linear two-stage residual inclusion model (95% CI 6-22, P<0.001). Treatment with anti-anaerobic antibiotics was again associated with fewer ventilator-free days, vasopressor free-days, and organ failure-free days.
"Most patients with sepsis do not have a specific indication for anti-anaerobic antibiotics, and our study suggests they could cause real harm," Chanderraj stressed. "Making the right antibiotic choice is not just a matter of preventing future antibiotic resistance -- these choices directly impact clinical outcomes for the patients in front of us."
Prior observational studies also found a mortality difference for piperacillin-tazobactam, Chanderraj noted. On the other hand, the recent randomized, controlled ACORN trialopens in a new tab or window, comparing piperacillin-tazobactam with cefepime, found that piperacillin-tazobactam did not increase the incidence of death among hospitalized adults, he pointed out.
The ACORN trial, however, only looked at 14-day outcomes and did not consider other anti-anaerobic antibiotics. "It was really designed to answer a very different question than our study," he explained. In a post-hoc analysis, Chanderraj and colleagues did look at 14-day outcomes and found no significant difference in mortality between piperacillin-tazobactam and cefepime -- similar to the ACORN trial.
The primary analysis of the current study included a final sample of 7,569 adult patients who presented to the emergency department at the University of Michigan from July 2014 through December 2018 and received empirical treatment with sepsis. (Patients with repeated admissions, who did not receive vancomycin, or who did not receive either piperacillin-tazobactam or cefepime treatment were excluded.) Of these, 4,523 were treated with vancomycin and piperacillin-tazobactam and 3,046 were treated with vancomycin and cefepime. The median age was 63 and 55% were men.
Importantly, a piperacillin-tazobactam shortage occurred during part of the study period, from June 12, 2015 to Sept. 18, 2016. The shortage allowed the researchers to conduct the retrospective study similar to a randomized trial because it affected which of the two antibiotics patients received at the study site, Chanderraj explained. As a result of the shortage, nearly all patients (97%) treated with piperacillin-tazobactam were admitted outside the shortage period, "enabling a direct comparison of the association between these antibiotics and 90-day mortality in a clinical practice setting," the authors wrote.
The study had some limitations. It relied on data from electronic medical records, but the authors emphasized that it had a good balance of covariates across treatment groups. Also, data was from a single center and may not be generalizable to other clinical settings or populations.
Disclosures
The study was funded by the National Heart, Lung, and Blood Institute, the National Institute on Aging, and the Agency for Healthcare Research and Quality.
Chanderraj reported no conflicts of interest; one study author reported receiving personal fees from Charles River Laboratories and Shionogi Pharmaceuticals.
Primary Source
JAMA Internal Medicine
Source Reference: opens in a new tab or windowChanderraj R, et al "Mortality of patients with sepsis administered piperacillin-tazobactam vs cefepime" JAMA Intern Med 2024; DOI: 10.1001/jamainternmed.2024.0581.
Rep. Cory Mills (R-FL) formally filed articles of impeachment against President Biden on Friday due to his recent comments about withholding deliveries of heavy bombs to Israel if it launches a major attack on "population centers" in Rafah, Gaza’s southernmost city.
Mills compared his move with the 2019 impeachment of then-President Donald Trump for briefly delaying weapons shipments to Ukraine and claimed Biden abused his power by trying to leverage military aid to get Israel to change its military tactics.
"In violation of his oath to faithfully execute the office of President and to uphold the Constitution, President Biden abused the powers of his office by soliciting a ‘quid pro quo’ with Israel while leveraging vital military aid for policy changes," Mills said in a statement, according to Fox News Digital.
"This egregious action not only compromised the credibility of the United States but also undermined the interests of our longstanding ally, Israel," Mills said.
"Therefore, President Biden’s conduct warrants impeachment, trial, removal from office, and disqualification from holding any future office under the United States," the statement added.
Over the past seven months, President Biden has staunchly supported the Israeli slaughter of Palestinians in Gaza by approving hundreds of arms deals and shipping tens of thousands of heavy bombs.
He has also provided political cover by vetoing UN Security Council resolutions for Israel and rejecting the International Court of Justice’s ruling that it’s "plausible" Israel is committing genocide.
While Biden warned he could withhold specific types of weapons from Israel, he still vowed the US would provide long-term military support for Israel. Members of his administration have also promised Israel will get all of the $17 billion in additional military aid that was recently authorized by Congress. But Republicans are still fuming over Biden’s comments.
Neurotechnology using artificial intelligence is opening up new possibilities in healthcare that previously didn’t exist.
For decades companies and researchers have been exploring implantable devices that interpret signals in the brain and translate them into words or physical commands. The technology is not new, but now, artificial intelligence is accelerating advances, allowing people affected by debilitating diseases to communicate in ways that were physically impossible before.
These devices have been game changers for people like Rodney, a patient living with ALS who had a Stentrode device implanted in his brain. The device, which was developed by Synchron, a neurotech company backed by Amazon’s Jeff Bezos and Microsoft’s Bill Gates, contains a tiny electrode that converts brain signals into physical actions, allowing Rodney to type on a keyboard using only his thoughts.
While neurotechnology can be empowering for patients like Rodney, AI could make less invasive neurotech more accessible for everyday consumers and spur the next generation of consumer-facing tech products.
According to Precedence Research, the market for neurotech devices was valued at around $15 billion in 2023, and it's projected to reach over $55 billion by 2032. That's a major reason why Big Tech companies like Meta (META) and Apple (AAPL) are backing research into devices that can decode thoughts and perceptions without requiring invasive surgery.
But as Big Tech moves ahead to build off neurotech advancements in the medical world, experts have cautioned that it could put our most valuable data — the privacy of our thoughts — at risk.
“This is our final fortress of privacy, and we've given up every other aspect of privacy that exists,” said Nita Farahany, a futurist, tech ethicist, and author of “The Battle for Your Brain.”
The Neuralink implant, which has over 1,000 electrodes and 64 threads, experienced a malfunction after a number of threads retracted from the brain, which decreased the number of effective electrodes. In a blog post, the company said this would not negatively impact how the implant works.
Musk is not the only CEO trying to make neurotechnology a reality. At least 30 companies are currently selling neurotechnology or developing the technology.
Apple, for instance, has a patent for AirPods with EEG technology embedded to measure brain activity. Given concerns over Apple’s sluggish iPhone sales, some investors are hoping the company will turn out exciting new products that will drive additional revenue.
Healthcare has long been a goal for Apple. CEO Tim Cook laid out this strategy in 2019, saying, “If you zoom out into the future ... and you ask the question, what was Apple's greatest contribution to mankind, it will be about health.”
Meta is another company funding a team of neuroscientists who are pushing this research further to understand how humans process language.
In one study conducted by Meta's Fundamental AI Research (FAIR) group, researchers flashed an image in front of participants for 1.5 seconds. Users seated in a neuroimaging machine thought of the image they saw, and AI was able to use that brain activity data to recreate the image.
The results weren’t perfect, as seen in the image below, but they were close enough that the research team initially thought the test was flawed.
On the left is the photo Meta's Fundamental AI Research team showed participants. The image on the right shows the image that AI reconstructed by decoding participants' brain activity.
“The first reaction was … let's try to find where we could have had some bugs that could explain the quality of these results,” King said.
King stressed that consumer-facing products are not the end goal of his research, and Meta says its aim is to “help people who have suffered traumatic brain injury to communicate.”
But at the same time, Meta CEO Mark Zuckerberg has made the company's neurotechnology ambitions clear since 2021, when he began touting an armband that uses electromyography to detect neural signals, allowing users to type and click on a screen with the subtlest of hand movements.
"I think we’ll start getting some consumer neural interfaces soon," Zuckerberg said in April. "I’m not talking about something that jacks into your brain. I’m talking about something that you wear on your wrist."
The privacy problem
There's a big question underlying all this research and product development: What does our world look like if Big Tech companies can literally read your mind?
Noninvasive brain-monitoring devices can be revolutionary in medicine for patients, but not everyone is thrilled by the prospect of Big Tech having access to peoples' thoughts.
Neurorights advocates believe our thoughts are the last piece of data we have left to ourselves. That’s why they are now fighting for legislation that would safeguard mental privacy while tech companies continue funding brain-scanning research.
"There's absolutely no regulation," said Dr. Rafael Yuste, a professor of biological sciences and neuroscience at Columbia University. "It's like the Wild West."
On July 6, 2024, electroencephalography (EEG), which measures the electrical activity of the brain, will celebrate its 100th anniversary. (Jacob Schröter/picture alliance via Getty Images) (picture alliance via Getty Images)
After years of research, Yuste discovered a way to control the thoughts of mice using lasers. The experiment scared him so much that he co-founded the Neurorights Foundation in an effort to safeguard thought privacy.
And already, concerns about the privacy implications of neurotechnology are driving policy change. In April, Colorado passed a bill that expanded the state’s privacy act to include neural rights — the first of its kind in the US. Similar legislation is also on the table in states such as California and Minnesota.
“The one space we have for mental reprieve is really our brains and mental states," Farahany said. "It's the kind of final piece of the puzzle.”
Farahany has a proposed framework for neurorights legislation that argues for more privacy overall, with “a right to self-determination over our brain and mental experiences.”
According to Farahany, it would still allow patients who want — and even need — neurotech to have access to it.
For Rodney's part, when I asked him via WhatsApp what he hopes his Stentrode device will accomplish long term, he thought back: “Hopefully, it will get to more people.”
Drugmaker mandates international banks for investor calls
Novo is investing to expand production of weight-loss drugs
Novo Nordisk A/S plans to sell bonds for the first time in more than two years to help finance its large program to expand production of its blockbuster treatments.
Novo would be testing the bond market for the first time since it became Europe’s most valuable company and a pop-culture phenomenon, sparked by excessive demand for its diabetes drug Ozempic and obesity treatment Wegovy.
The retailer is a key indicator of how consumers are holding up, providing a sharper lens on household spending in comparison with the government's consumer price index, which showed that inflation ticked up more than expected in March.
Telsey Advisory Group estimates the retail behemoth will have solid results during the first fiscal quarter as higher-income shoppers spend more at its stores because of inflationary pressures, the firm wrote in a note Friday.
"Walmart should also benefit from trade down, as lower income consumers continue to shop value-priced categories and private brands, and upper income consumers spend more at Walmart in search of value," the analysts wrote.
Last quarter, John David Rainey, Walmart's chief financial officer, elaborated on the uptick in richer customers.
"One of the biggest contributors in the quarter was in this income demographic from households that make more than $100,000 a year," Rainey said during the company's earnings call. "Our value proposition is resonating with customers, and they're clearly shopping us in new ways versus how they have historically."
Walmart shares are up 15% this year, outperforming the S&P 500's 9.5% rise.
Walmart
Many chief executives have already told analysts their companies have taken a hit in profits from persisting inflation, which has fallen considerably from a peak of 9.1%, but progress has largely flatlined since the summer.
To better cater to money-conscious consumers and boost traffic, companies have been competing with each other to roll out tantalizing promotions.
For one, the head of Dine Brands, parent company of Applebee's Neighborhood Grill & Bar, International House of Pancakes (IHOP) and Fuzzy's Taco Shop, said it launched deals like $1 margaritas.
"The consumer sent a message this past quarter. It was a tough quarter for us, and it was a tough quarter for the restaurant industry overall," CEO John Peyton said during an appearance on "The Big Money Show."
About 40% to 45% of its guests dined out less frequently in the first quarter, and when they did, they "managed their wallet more closely than in the past, finding our promotional offers and things like that," he explained.
Aldi, meanwhile, recently announced it's cutting prices on more than 250 items through Labor Day to help consumers contending with "stubborn inflation."
McDonald's CEO Chris Kempczinski also told analysts on an earnings call last month the "consumer is certainly being very discriminating in how they spend their dollar" due to inflation.
"And while it may feel — it may be more pronounced with the lower-income consumer — I think it's important to recognize that all income cohorts are seeking value. And so our focus is on making sure, as I said, that we're offering strong value to our customers," Kempczinski said.
The challenge, though, is how to differentiate within an environment with so many companies offering promotions, according to Kempczinski.
"I think the issue that we have in the U.S. is in an environment where everybody is out there with a value message," he said. "There's an opportunity for us to drive better awareness of what our value platform is."
Wall Street will digest two economic reports next week with the producer price index on Tuesday and the consumer price index the following day.
