COPD Inhalers' Link to Fracture Risk Supported in Pooled Trials

 Chronic obstructive pulmonary disease (COPD) treatments involving inhaled corticosteroids (ICSs) were associated with a greater risk for fractures, a meta-analysis of several dozen randomized trials found.

Use of inhaled ICSs was associated with a 19% increased fracture risk when compared to treatment without ICSs (RR 1.19, 95% CI 1.04-1.37), and that risk held steady when treatment lasted 12 months or more, reported Ruiying Wang, MD, of Shanxi Medical University in China, and coauthors in BMC Pulmonary Medicineopens in a new tab or window.

No increased risk was observed for ICS monotherapy, and the overall link appeared greater when ICS was used in combinations, such as with a long-acting beta-agonist (LABA) or as triple therapy with a LABA plus long-acting muscarinic antagonist (LAMA):

• ICS alone: RR 1.07 (95% CI 0.86-1.33)
• ICS/LABA: RR 1.30 (95% CI 1.10-1.53)
• Triple therapy: RR 1.49 (95% CI 1.03-2.17)

"Currently, it is still controversial that inhaled corticosteroids increase the risk of fracture in patients with COPD. Whether inhaled glucocorticoids increase the risk of fracture in patients with COPD may depend on the timing, dose, and dosage form of the ICSs treatment," Wang and colleagues said.

Subgroup analysis showed that the predictors of fractures were budesonide in high doses via metered-dose inhaler devices, whereas fluticasone furoate and fluticasone propionate in different inhalation devices had no relationship with increased fractures.

The investigators noted that COPD patients tend to be elderly and have various complications, and long-term inhalation of glucocorticoids may increase their risk of fractures.

"The exact mechanisms by which ICSs increase the risk of fracture in COPD patients are unclear. However, due to malnutrition, inflammatory response, and previous exposure to corticosteroids, COPD patients are at risk of fracture porosity and fracture," study authors wrote.

"Long-term and intensive ICS therapy may lead to a small part being absorbed and have systemic effects, resulting in increased bone absorption and decreased bone formation. Moreover, osteoporosis is an important complication of COPD," they added.

Included in the meta-analysis were 44 randomized clinical trials totaling 87,594 patients.

Meeting inclusion criteria were studies that included patients with COPD, treatment interventions including any kind of inhaled glucocorticoids, utilizing non-ICS treatments as a control, and trials that reported fracture events in their results. Observational reports, studies with patients who had asthma or unknown diagnoses, and studies where ICSs were involved in both study cohorts were not included.

Studies were retrieved in October 2022 and were updated in November 2022. Of the 44 trials analyzed, 31 evaluated ICS/LABA therapy compared with control groups (including LAMA only, LABA only, LAMA/LABA, or placebo groups), while 13 evaluated triple therapy in comparison to control groups (including LAMA only, LABA only, LAMA/LABA, or placebo groups). Follow-up periods of the studies ranged from 3 to 36 months.

Factors associated with an increased risk of fracture were average participant age of 65 or above (RR 1.27, 95% CI 1.01-1.61) and Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage III disease (RR 1.18, 95% CI 1.00-1.38).

Limitations to the meta-analysis include lack of fracture classification, possible publication bias as a result of manual retrieval, as well as the heterogeneity in how each randomized trial could report complications and medical histories.

Nevertheless, the pooled data have value as several large-scale randomized controlled trials have already individually failed to link ICSs and fractures directly, and trials tend to exclude people with severe fracture porosity and fractures, authors of the meta-analysis argued.

"Therefore, the impact of ICSs on fracture risk in patients with COPD may be significantly greater in the real-world," Wang and colleagues said.

Disclosures

Study authors declared no funding source and no competing interests.

Primary Source

BMC Pulmonary Medicine

Source Reference: opens in a new tab or windowPeng S, et al "Effect of fracture risk in inhaled corticosteroids in patients with chronic obstructive pulmonary disease: A systematic review and meta-analysis" BMC Pulm Med 2023; DOI: 10.1186/s12890-023-02602-5.

https://www.medpagetoday.com/pulmonology/smokingcopd/105974

Coronary Disease May Come With a Donor Heart

 Coronary artery disease (CAD) that comes with a donor heart was not uncommon and conferred cardiovascular risk, although not an early death overall, according to data from a large Spanish registry.

Prevalence of CAD transmitted to recipients of heart transplantation was 18.3%, with a 6.9% rate of significant disease marked by stenosis of 50% or more in epicardial coronary arteries, reported David Couto Mallón, MD, of Hospital Universitario de A Coruña in Spain, and colleagues in the Journal of the American College of Cardiologyopens in a new tab or window.

Over a mean 6.3 years of follow-up, this donor-transmitted CAD didn't independently predict all-cause mortality (adjusted HR 1.44, P=0.141), but it did correlate with cardiovascular mortality (adjusted HR 2.25, P=0.011) and combined risk of cardiovascular death or nonfatal major adverse cardiovascular events (adjusted HR 2.42, P<0.001).

These findings came from cardiac transplant patients in Spain largely without donor coronary angiograms to exclude donor-transmitted CAD; "this helps us clarify an important controversy: the relevance of [donor-transmitted] CAD in heart transplant patients," noted Richard Cheng, MD, of the University of California San Francisco, and colleagues in an accompanying editorialopens in a new tab or window.

"These findings, showing no differences in mortality, do support the use of donor hearts with atherosclerosis, although the increased hazard for cardiovascular death and hospital admission for graft dysfunction does suggest the need for caution and more data," they concluded.

The researchers agreed: "The reduced number of patients in whom [significant donor-transmitted] CAD was detected may be [one] of the reasons why differences in the primary outcome did not reach statistical significance; however, our findings suggest that the acceptance of hearts from donors with high cardiovascular risk might be considered for a selected group of patients, such as those whose conditions are deteriorating while they are on the waiting list and for whom LVAD [left ventricular assist device] therapy as a bridge to transplantation is not feasible, or those on an urgent HT [heart transplantation] list."

Based on small prior studies, professional society guidelines have recommended against the use of hearts from donors with known CAD. Even with donor angiogram screening, though, significant donor atherosclerosis can be overlooked, Cheng's group pointed out.

Indeed, the heart listing criteria instituted in 2018 have led to higher clinical acuity at time of transplant, which "may favor accepting donor hearts with more uncertainty, such as older donors with moderate or less atherosclerosis, or those without angiograms," they added.

Moreover, the increase in heart transplants from donors after circulatory death (thanks to ex vivo perfusion and normothermic regional perfusion) means more cases in which donor angiograms are unlikely to be available, unlike those of donation after brain death, for which donor angiograms are routine or can be readily requested, they noted.

"Consideration should be given to more frequent ischemic evaluation and surveillance coronary angiography in patients who received a donor heart without a donor angiogram and/or of older age," Cheng and colleagues suggested.

More research is needed to determine whether percutaneous coronary intervention (PCI) can mitigate the risks from donor-transmitted CAD, they added.

The retrospective DONOR-CAD cohort study included 1,918 consecutive adult cardiac transplant patients from January 2008 through December 2018 at 11 centers in Spain, where angiography of the donor heart was not routine. Just 0.4% of the hearts had pretransplant coronary angiograms. For those that didn't, the reason was not documented for the vast majority, although the researchers pointed out that noninvasive investigation of CAD might have been selected in some patients.

The analysis included only the 937 recipients (48.9%) who had coronary angiography within 3 months after transplantation (median 42 days).

Mean donor age was 45 years. Donor hearts with significant CAD were more likely to come from donors who were older, men, had diabetes, and had died of a cardiovascular accident or a stroke. However, neither donor nor recipient age interacted with the association (or lack thereof) between transmitted CAD and all-cause mortality.

Among the 65 patients who had significant CAD seen on angiography, five received conservative treatment, 36 were tested for ischemia (all negative), and 24 underwent revascularization. The sole death among the intervention patients was in the only patient to have coronary artery bypass graft surgery.

"Numbers were too small to determine whether PCI mitigates cardiovascular death," Cheng and colleagues noted, "although we have previously published that the use of second-generation drug-eluting stents for CAV [cardiac allograft vasculopathy] is not only feasible but also associated with excellent stent patency, and with careful clinical and angiographic surveillance and follow-up, seem to normalize survival with similar survival compared with patients without significant CAV in landmark analysis."

The researchers cautioned that the study was affected by selection bias, which could have led to an underestimation of the true prevalence of donor-transmitted CAD. Other limitations included that follow-up wasn't as long as median survival for these patients and that certain variables, like serum lipids, were missing.

With more data on safety of transplant with donor-transmitted CAD, it may be possible to incorporate noninvasive or invasive stress testing and develop risk scores to allow more routine use of older donors after circulatory death who had mild focal atherosclerosis or no donor coronary angiograms and thus further expand access for patients waiting on the transplant list, the editorialists speculated.

Disclosures

Couto-Mallón disclosed research grant funding from the Fundación Mutua Madrileña for the study, which was also supported by European Union Regional Development Funds.

Co-authors and editorialists disclosed no relevant relationships with industry.

Primary Source

Journal of the American College of Cardiology

Source Reference: opens in a new tab or windowCouto-Mallón D, et al "Prevalence, characteristics, and prognostic relevance of donor-transmitted coronary artery disease in heart transplant recipients" J Am Coll Cardiol 2023; DOI: 10.1016/j.jacc.2023.06.016.

Secondary Source

Journal of the American College of Cardiology

Source Reference: opens in a new tab or windowCheng R, et al "Donor-transmitted coronary artery disease: another avenue to expand heart transplantation?" J Am Coll Cardiol 2023; DOI: 10.1016/j.jacc.2023.07.001.

https://www.medpagetoday.com/cardiology/hearttransplantation/105987

Maui Fires: A Forensic Pathologist's Perspective on the Aftermath

 Death investigation in Maui County, Hawaii is managed by the police, and the chief of police is the coroner

opens in a new tab or window. In 2015, I interviewed for a job there: an open position for a forensic pathologist to perform autopsy death investigation. My husband took the kids to the mall to shop for sunscreen and bathing suits while I was in the interview; we were there on a family vacation. Maui was paradise to us.

When you apply for a job in forensic pathology, some of the process is just like that for any other job. I asked about the routine things that would make our lives possible in a new place -- salary, relocation costs, the best schools. We had been to Maui a few times before as tourists. Our entire family had fallen in love with the islands, over and over. The idea of living and working in Hawaii was enticing. The morgue I would be working in was in the hospital complex and I recall two autopsy tables. The job description stated that I would perform approximately 220 to 240 postmortem examinations per year, with only two to four homicides, "...and probably more 'nature-related' accidents (ocean fatalities, hiking accidents, etc.) than most locales." The salary was lower that what I expected, given the high cost of living, but colleagues who had done it referred to that pay drop as "island tax" -- the price of living in paradise.

Now, looking back at that job description after the catastrophic wildfires, my heart aches and my stomach lurches. A morgue with only one forensic pathologist used to doing one or two autopsies per day cannot hope to handle the scope and magnitude of body recovery and death investigation work engendered by this disaster. Even if you fly in the Federal Emergency Management Agency (FEMA) or a federal Disaster Mortuary Operational Response Team (DMORT) -- with their refrigerated trucks, mobile morgue, pathologists, anthropologists, technicians, and morticians -- the lack of local mass fatality experience is going to make coordinating those resources and personnel extremely challenging, even for the most experienced and best-drilled locals. FEMA and DMORT bring resources, but they're not meant to manage the disaster

opens in a new tab or window. That has to be done by the local, county, or state authorities in the affected region. Compounded with the displacement of so many of their own workers and the entire community's grief over the loss of loved ones and whole swathes of homes, businesses, and cultural institutions, the pressure coming down on local agency managers will be tremendous. The head of Maui's emergency management agency resignedopens in a new tab or window for health reasons in the immediate aftermath of the fires, and his replacement is being sought. A challenging aftermath lies ahead.

Aerial images of Lahaina -- former capital of the Kingdom of Hawaii and a lovely, historic port town of 13,000 people -- look like a war zone. Most of the buildings have collapsed and burned to the ground. Ash and debris cover the earth. But in my experience, you still cannot comprehend the scale of a disaster such as this from photos -- you have to be on the ground to see it and smell it and feel it. With your feet on the ground you breathe the toxic air, feel the pulverized rubble and heat-shattered glass, assess the impediments to transport, and experience first-hand the difficulties in communicating in an environment where networks have literally melted down. On the ground, it's a vast field of ruin, and somewhere in there are human remains that no longer resemble anything human.

One of the biggest challenges to the recovery of these remains in the ruins of Lahaina will be in finding and accurately counting them. The missing currently number over a thousand, and when decedents are located in the rubble, their bodies may not have any identifying features due to the destructiveness of the blaze. Fires rarely incinerate human bones completely, but under the temperatures that the Maui fires generated, bones will become very fragile. They look like black chalk, and are hard to distinguish from surrounding debris like concrete and charred drywall. Over 40 trained cadaver-detection dogs have been brought into Lahaina and are currently doing their job, guiding forensic anthropologists -- experts in the identification and recovery of human skeletal remains. When bones and other remains are found, the anthropologists will have to first confirm they are human. Then they will work carefully to contain the immolated remains of each person along with any identifying property, so the fragments stay together throughout the recovery process. There are limited numbers of people with the skill set to do this, and well-meaning volunteers might end up inadvertently complicating or even ruining the identification process if they try. If victims of the fire had huddled together for safety and died in groups, then the commingling of their body parts will make the separation of the remains and the identification of each and every person more difficult.

With communications down, families all over the island are having difficulty reaching one another, thus increasing the list of missing persons. Once the missing are identified, living or dead, their families may have lost their homes and relocated, and may not be reachable. Tourists frequent the islands year-round, but especially in summer, and some of those will be foreign nationals. DNA exemplars will need to be sent internationally to confirm identification. So, while current DNA technology can identify an individual in about 30 minutes, it will be getting the samples from the living relatives that will slow the process down considerably.

Given the news reports of the geographic scaleopens in a new tab or window of the devastation (over 2,000 acres and 2,200 structures, most of which are residential), it may be many weeks to months before everyone is even found. Given the intensity of these fires, some bodies may not be identifiable at all using scientific modalities; fire can destroy everything we're made of, even our DNA. We also know there were many people who escaped the fires by jumping into the ocean under a nightshade of black smoke, into waves whipped up by hurricane winds. Many of them will have perished there, and some of their bodies may have been swept away forever. So we might find, as we found during the recovery effort after the September 11 attacks, that some of the victims might need to be presumed dead based on circumstances, and declared legally dead without evidence of a body.

I worked on the 9/11 recovery effort on the island of Manhattan. The scenes I'm seeing on the island of Maui bring those experiences back to me now. A disaster like this one unfolds over hours, but the devastation to a community will have repercussions for years to come. With donations, federal support, and a whole lot of aloha, I am hopeful that Lahaina will rebuild and return to paradise.

Here is a linkopens in a new tab or window to a GoFundMe from the company that runs the condo complex where our family used to visit and hope to again, for staff who lost their homes in Lahaina.

Judy Melinek, MD, is an American forensic pathologist and the CEO of PathologyExpert Inc. She is currently working as a contract pathologist in Wellington, New Zealand. She is the co-author with her husband, writer T.J. Mitchell, of the New York Times bestselling memoir Working Stiff: Two Years, 262 Bodies, and the Making of a Medical Examineropens in a new tab or window, and two novels, First Cut and Aftershock, in the Jessie Teska forensic detective series.

https://www.medpagetoday.com/opinion/working-stiff/105982

'NYC Health Chief Aims to Redefine Public Health Post-COVID'

 Public health has endured a very public critique during the acute crisis of the COVID-19 pandemic and its aftermath.

Now, public health leaders are tasked with the difficult challenge of digesting those lessons and shaping the field into a new and improved version of itself.

Among them is Ashwin Vasan, MD, PhD, Commissioner of the New York City Department of Health and Mental Hygiene (DOHMH), who took the helm almost 18 months ago and has already started making changes at the agency, aimed at setting up the city for future public health success.

"We've always been a city that celebrates and supports public health," Vasan told MedPage Today in a recent interview. "But the issues are similar [to what's going on across the country]: community engagement and trust building, getting out of the ivory tower ... and into the community."

Vasan discussed those challenges, and his plans for addressing them, in a conversation with MedPage Today in mid-August. He says he's looking externally at the city's public health needs to inform any internal changes.

"We're trying to bring the external focus and the internal focus into alignment because we know we can't achieve [our external goals] if we don't reform internally," Vasan said.

Modernizing Public Health

During the first year of his tenure, Vasan and his teams identified external public health issues to inform the best internal structure for the agency going forward.

The key statistic that stood out to him was the significant drop in life expectancy in the city.

"We lost nearly 5 years of life expectancy in 2020, and in 2021 we gained about half back, but it's not inevitable that we'll just get back on track and be at our pre-COVID levels," Vasan noted. "We're seeing rates of excess death, premature death, and death in vulnerable populations ... worsen."

He said the key question informing his approach is, "How do we organize our strategy around getting back those life-years and ensuring equity?"

Part of that process is developing a population health agenda for the city that establishes numerical goals for each of the leading causes of death in those three categories, to improve those rates by 2030 and beyond, Vasan said.

Several internal changes are needed to make that happen, he explained, highlighting five key areas. These include investing in a stronger workforce, both for current workers and for recruiting new workers.

Another, he said, is ensuring that equity is baked into the infrastructure, making it a "part of every single program at the agency."

It's also about improving communications and external affairs, he added. "How do we really engage people? How do we build that trust? How do we get out of our offices and into communities to build relationships -- and understand that this simple act can pay off for a long time, especially when you're asking something of communities, like wearing a mask or taking a vaccine? If you've never spent any time with people, it's much harder."

It also requires building data systems that can deliver important information sustainably, Vasan said.

"We did incredible things during COVID around data dashboards, but when you look at the work it took underneath, it's not sustainable," he noted. "It's highly manual and highly circumstantial. And a lot of it was highly funded by emergency federal dollars that are now disappearing."

Perhaps one of the biggest changes Vasan has made is creating a Chief Program Officer position, tasked with unifying the department's many division and subject matter experts.

"Most health departments are organized in a fairly flat way, and we decided we need a unifying body that's thinking interdisciplinarily across subject matter divisions," he said.

The intention is to think of the work as shared services, and it's been called "one DOHMH" to note the need to work as one entity, he continued. He's also created an executive leadership team that focuses more on these big agency questions.

Culture Change

Vasan wants to bring more of a crisis-management mindset to the department's daily work structure. When health departments face an emergency, they create an incident command structure "and they pull people from all over the agency into a new command structure to work on the crisis," he explained.

Crisis times also usually mean people are more comfortable working "quickly with imperfect information," he added, and there's less fear of failure.

"How do we start working more like that in non-crisis times?" he asked. "We've shown what we can do when we draw upon the strengths of this whole beautiful agency. Why can't we do that day-to-day?"

"There are sensible things we can do to create new structures which beget smart functions and ways of working that benefit all of us," he pointed out.

Vasan said there's also a scholastic or academic focus on public health, "but we have to remember that we are public servants first."

"The academic-driven culture of public health has to evolve," he said. "That's not to say we stop publishing or doing great research, but we have to put it in the right place. Taxpayers pay us, and we have a responsibility to the public, so we have to think about programs first, results first, and accountability first. With that, you'll have plenty of opportunities to write, be thought leaders, and advance the science."

"Scholasticism is not an end in-and-of-itself, but a byproduct of great work serving people," he added.

It's not necessarily easy to implement such culture change at a large bureaucracy -- the department has 7,500 employees and a $2 billion budget -- but Vasan called it a work in progress.

Part of selling the changes involves "coming up with examples of where better communication, better collaboration, better awareness and visibility can improve the product," he said. A goal is to have employees trust that working differently is "helping us elevate their work in a more strategic way."

City public health employees are "smart enough to know that public health has been under a lot of stress," he noted, "and it's time to pivot, to evolve, to take the next step forward and redefine public health for this new era."

https://www.medpagetoday.com/special-reports/exclusives/105996

'Our High Misdiagnosis Numbers Aren't All That Shocking'

 According to a recent report

opens in a new tab or window from the Johns Hopkins Armstrong Institute Center for Diagnostic Excellence, 795,000 Americans a year die or are permanently disabled after being misdiagnosed (371,000 patients die and 424,000 are permanently disabled). While previous estimates of annual incorrect diagnoses and their impact on people's lives have tended to vary widely, this new research provides a more clear picture of the burden of misdiagnosis.

But there is little comfort in the report's staggering numbers. While it is frightening to think that so many people suffer because of medical errors, it's not all that surprising that this is happening.

Here are a few reasons (which you may already be intimately familiar with) why these numbers shouldn't surprise us.

The Complexity of Medicine

It's an understatement to say that medicine is a complex field, and doctors are faced with an enormous amount of information to process each day. Doctors must fully consider a patient's medical history, symptoms, test results, and other factors when making a diagnosis. With so much information to consider, it's unsurprising that mistakes can and do happen.

When I spoke with Florida medical malpractice lawyer Greg Yaffa, JD,opens in a new tab or window it was clear he recognized the complexities of medicine and the things that can go wrong when doctors deviate from the standard of care. "Part of being a medical doctor is understanding the nuances and impact of differing conditions and recognizing the right protocol to follow when those conditions present in their patients."

Limited Time

Doctors are often under pressure to see an overwhelming number of patients in a limited amount of time. This can lead to rushed diagnoses and missed details. There are no easy answers to limited time, but it's important to understand that this crunch is often a catalyst for mistakes.

Lack of Communication

This issue isn't discussed anywhere near enough. Just as miscommunication between pilots and other crew members and air traffic control is a catalyst for airline disasters, where there is a breakdown in communication between doctors, nurses, and other healthcare professionals, things go wrong fast. If a doctor fails to communicate important information to a specialist, the specialist may diagnose based on incomplete information, and things can spiral from there.

Yaffa added, "The consequences of miscommunication among medical professionals can be catastrophic, leading to misdiagnosis, medication errors, and preventable complications. In my experience, I have witnessed firsthand how the breakdown of vital information exchange can have devastating effects on patients' lives. Bridging the communication gap isn't just a matter of professional responsibility; it's an imperative that safeguards trust, accountability, and ultimately, the well-being of those seeking medical care."

Diagnostic Errors in Emergency Rooms

Another reportopens in a new tab or window highlighted the reality of emergency rooms being particularly prone to diagnostic errors, with hundreds of thousands dying each year due to misdiagnosis. The top five conditions that are often misdiagnosed in emergency rooms are stroke, heart attack, aortic aneurysm/dissection, spinal cord compression/injury, and venous thromboembolism.

Doctors Are Just People

When we look holistically at all the moving parts of any medical procedure in a hospital, it's unsurprising that things go wrong -- there are so many opportunities for human error. We can't change the fact that people, including doctors, are imperfect. People being people can contribute to catastrophic errors. It's just not something that, in the immediate future, will be taken out of the equation.

The good news is that steps can be built into the process to reduce the incidence of misdiagnosis. Doctors can be given more time to see patients, communication between healthcare professionals can be improved, and technology can be used to help doctors make more accurate diagnoses.

Having seen many different malpractice scenarios over the years, Yaffa suggests three steps that every physician should take as a matter of course to reduce their medical malpractice risk exposure:

1. Maintain accurate medical records: Make sure medical records are properly documented by all treating providers, and whenever possible, update records in real-time to avoid mistakes such as medication errors and misdiagnosis.
2. Take more time with patients before and after care: In an ideal world, doctors would have virtually unlimited time to hear and fully address patient concerns. The more heard a patient feels and the stronger the doctor-patient relationship, the better. While time is always a challenge, remember to use your time wisely to listen to patients and make them feel as though you've gone above and beyond to provide quality care.
3. Conduct better follow-up: It's important for physicians to continue engaging with their patients even after they've been discharged from the medical facility. This practice helps ensure that issues are caught and resolved quickly. The earlier doctors identify issues before and after discharge, the lower the likelihood of malpractice occurrences.

Misdiagnosis stories will never leave our collective news cycles, but sometimes one extra, particularly diligent, step is the difference between our actions or inactions becoming a statistic.

Aron Solomon, JD,opens in a new tab or window is the Chief Legal Analyst for Esquire Digitalopens in a new tab or window and the editor of Today's Esquireopens in a new tab or window. He has taught entrepreneurship at McGill University and the University of Pennsylvania, and was elected to Fastcase 50, recognizing the top 50 legal innovators in the world.

https://www.medpagetoday.com/opinion/second-opinions/105995

Regeneron gets federal funding for next-generation COVID treatment

 Regeneron Pharmaceuticals Inc. (REGN) said Tuesday that the Biomedical Advanced Research and Development Authority has agreed to support the development, manufacturing and licensure of a next-generation COVID-19 monoclonal antibody. The agreement, part of the U.S. Department of Health and Human Services' Project NextGen initiative, provides up to $326 million of government funding, Regeneron said, noting that the federal agency will fund up to 70% of Regeneron's costs for certain clinical development activities for the therapy. Regeneron's most advanced antibody candidate under the agreement is expected to enter clinical trials later this year, the company said in a release. Regeneron has previously worked with BARDA, which is part of the Health and Human Services Department's Administration for Strategic Preparedness and Response, on new treatments for Ebola as well as COVID-19. Regeneron shares were down 0.3% Tuesday and have gained 16.7% in the year to date, while the S&P 500 is up 14.4%.

https://www.morningstar.com/news/marketwatch/20230822332/regeneron-gets-federal-funding-for-next-generation-covid-treatment

Lilly: Superior Progression-Free Survival for Thyroid Cancer Therapy

 Eli Lilly and Company (NYSE: LLY) today announced topline results from the LIBRETTO-531 study evaluating Retevmo versus physician's choice of the multikinase inhibitors (MKIs) cabozantinib or vandetanib as an initial treatment for patients with advanced or metastatic rearranged during transfection (RET)-mutant medullary thyroid cancer (MTC). The study met its primary endpoint, demonstrating a statistically significant and clinically meaningful improvement in progression-free survival (PFS). This result was based on a pre-specified interim efficacy analysis conducted by an independent data monitoring committee (IDMC). Adverse events observed on Retevmo were generally consistent with those identified across the previously reported Retevmo development program (LIBRETTO-001, LIBRETTO-121, LIBRETTO-321).

https://www.biospace.com/article/releases/lilly-s-retevmo-selpercatinib-demonstrates-superior-progression-free-survival-compared-to-approved-multikinase-inhibitors-in-ret-mutant-medullary-thyroid-cancer/