In a livestreamed meeting Tuesday afternoon, Health Secretary Robert F. Kennedy Jr. drew a dark portrait of the state of America’s health while addressing the MAHA Commission’s most recent report, which includes plans to research potential links between vaccines and rising rates of chronic disease.
The Make America Healthy Again Commission released its second report Tuesday, complete with recommendations on diet, against overmedication and plans to research a potential connection between vaccines and the rising rate of chronic disease. At a livestreamed MAHA Commission meeting, Health Secretary Robert F. Kennedy Jr. painted a dire picture of the state of the country’s health.

“We are now the sickest country in the world,” Kennedy said. “We have the highest chronic disease burden of any country in the world, and yet we spend more on health care than any country in the world.” The secretary went on to say that 76.4% of Americans are suffering a chronic disease compared to 11% when his uncle, John F. Kennedy, was president between 1961 and 1963, despite the U.S. spending two to three times that of European nations on healthcare.

The MAHA Commission, created by President Donald Trump in February with a mission to overhaul the country’s food supply and chronic health outcomes, previously published a 73-page report in May focused on many of the same key points. It was quickly revealed by the nonprofit news organization NOTUS that the report was riddled with errors, including the citing of at least seven nonexistent studies.

On Tuesday, Kennedy listed several other statistics, without providing evidence or citations for them, including that American girls are hitting puberty six years earlier than they have historically. In the report, entitled “Make Our Children Healthy Again,” the authors write that “children are particularly vulnerable to chemicals during critical stages of development—in utero, infancy, early childhood, and puberty.”

Kennedy added that the U.S. has lost “six years of lifespan to Europe in the past 20 years,” that “our young men have sperm counts that are half of what they ought to be,” and that diabetes is now endemic in the country, again without providing citations. Autism rates, Kennedy contended, have increased from one in 10,000 in 1970 (the report attributes this statistic to 1960) to one in every 31 children today.

The MAHA report lays out four potential drivers behind the rise in childhood chronic disease: poor diet, aggregation of environmental chemicals, lack of physical activity and chronic stress, and, of particular interest to the pharmaceutical industry, overmedicalization.

“There is a concerning trend of overprescribing medications to children, often driven by conflicts of interest in medical research, regulation, and practice,” the report reads. “This has led to unnecessary treatments and long-term health risks.”

Later in the meeting, Health and Human Services deputy secretary Jim O’Neill—who also took over as acting CDC director after the controversial ouster of Susan Monarez late last month—took the microphone.

“Under Secretary Kennedy, HHS supports rigorous science and radical transparency, and we need that everywhere, but nowhere is that more pressing or more valuable than CDC,” O’Neill said. “Over the past 15 years, sadly, CDC presided over rising chronic disease and flatlining longevity and trust in our public health agencies collapsed.”

“We’re working to refocus CDC to its original 1946 mission of protecting Americans from infectious disease,” O’Neill added.

In an op-ed published last week in the Wall Street Journal, Kennedy outlined a new structure in which the CDC would prioritize infectious disease over other forms of disease control, while breaking out the management of chronic disease programs into a new Administration for a Healthy America.

On the vaccines front, the MAHA report emphasized what it described as “the growth of the childhood vaccine schedule,” which has expanded from three to 29 injections since 1986, including in utero exposures, by 1 year of age. This number of shots exceeds that of many European nations, according to the report, which notes that Denmark has nearly as many as the U.S.

The report calls for vaccine clinical trials with “more rigorous clinical trial designs,” including the use of true placebo controls, larger sample sizes and longer follow-up periods, to further understand vaccine safety and any links to chronic disease, as well as changes to the vaccine safety surveillance system.

“Tools that are meant to fight disease, such as vaccines, antibiotics and therapeutics can save lives, can also trigger adverse events in some patients and that truth must no longer be denied or distorted,” O’Neill said.

Dengue, a mosquito-borne viral disease that infects an estimated 100 million people globally each year, is notorious for its unpredictable severity. Some people experience little more than a fever and rash, while others progress to life-threatening bleeding or organ failure. Now, a new study led by Duke-NUS Medical School in Singapore reveals that the virus can leave a lasting genetic “imprint” on the immune system—one that reshapes how people respond to future infections and vaccines.

The study, published in Med and titled “Dengue virus infection reprograms baseline innate immune gene expression,” shows that, unlike vaccination, natural dengue infection reprograms innate immune cells. This trained immunity may help explain why vaccines work better in people with prior exposure to the virus.

Infection versus vaccination

Researchers analyzed blood samples from volunteers in the United States. Participants received Takeda’s TAK-003 dengue vaccine in a clinical trial, and their immune responses were compared to those who had previously been infected with dengue. “To understand the underpinnings of the difference in antibody response to TAK-003 [live-attenuated tetravalent dengue vaccine] vaccination in baseline seronegative and seropositive individuals, we profiled whole-blood mRNA using a full-genome microarray. The number of differentially expressed genes (DEGs) and their expression kinetics were both qualitatively and quantitatively different between seronegative and seropositive subjects after the first of two TAK-003 doses,” wrote the authors.

Later on, the researchers expanded the study to Singapore: “To ensure that our findings were not biased by a single small cohort, we included two separate prospectively enrolled cohorts of healthy volunteers in Singapore. The first cohort (enrolled by Kalimuddin) included healthy volunteers in a study on the host response to the live-attenuated yellow fever vaccine (YF17D-204), and the second (enrolled by Low) had healthy volunteers who participated in a study to validate baseline transcriptome differences observed from the DEN-210 cohort. Anti-dengue immunoglobulin (Ig)G ELISA was used to differentiate volunteers into seropositive or seronegative for dengue.

They found that even before vaccination, dengue-experienced individuals displayed distinct gene activity patterns. “Our findings show that natural dengue infection can leave a lasting genetic imprint on the immune system,” said Eugenia Ong, PhD, principal research scientist at Duke-NUS and first author of the study. “Instead of returning to normal, the immune system resets into a new baseline—one that may explain why second infections are often more severe.”

Why vaccines work better post-infection

This immune “reset” means that in people who had prior dengue infection, a single dose of the vaccine triggered stronger antibody responses than two doses did in dengue-naïve individuals. As the authors wrote in Med, “while a single DENV infection reprogrammed the gene expression of innate immune markers…vaccination did not show evidence of similar innate immune reprogramming.”

Senior author Eng Eong Ooi, PhD, from the Emerging Infectious Diseases Program at Duke-NUS Medical School, compared the phenomenon to athletics: “Think of it as training for a sport—the immune system only gets a real workout from the full game—the equivalent of a natural infection. A light warm-up from vaccination isn’t enough to reprogram it.”

Implications for vaccine strategy

The findings clarify why dengue vaccines are more effective in individuals who have already had dengue. They also highlight why an “imperfect” vaccine can still be used safely to reduce disease burden.

Patrick Tan, MD, PhD, professor and senior vice-dean for research at Duke-NUS, emphasized the broader significance: “As dengue continues to affect millions across Asia, Latin America, and other tropical regions, this study closes a critical gap in our understanding of how infection reshapes the immune system. These insights are vital not only for developing better vaccines but also for guiding global and national health policies.”

By identifying how dengue alters innate immunity, the study paves the way for designing next-generation vaccines that can mimic the infection’s imprint without the risks of disease. While researchers caution that a perfect dengue vaccine may still be a decade away, their findings strengthen the case for deploying current vaccines to safely prevent millions of cases worldwide.

Researchers from University of California San Diego Sanford Stem Cell Institute have discovered that spaceflight accelerates the aging of human hematopoietic stem and progenitor cells (HSPCs), which are vital for blood and immune system health.

The team used automated artificial intelligence (AI)-driven stem cell-tracking nanobioreactor systems to track stem cell changes in real time, during four SpaceX Commercial Resupply Services missions to the International Space Station (ISS). The findings showed that the cells lost some of their ability to make healthy new cells, became more prone to DNA damage, and showed signs of faster aging at the ends of their chromosomes after spaceflight—all signs of accelerated aging.

The findings have implications not just for astronaut health, but also for understanding the mechanisms of aging and age-related diseases, such as cancer, on Earth. The results also underscore the need for new countermeasures to protect stem cell function during extended space missions and support the development of biological markers to detect stress-induced aging early.

“Space is the ultimate stress test for the human body,” said research lead Catriona Jamieson, MD, PhD, director of the Sanford Stem Cell Institute and professor of medicine at UC San Diego School of Medicine. “These findings are critically important because they show that the stressors of space—like microgravity and cosmic galactic radiation—can accelerate the molecular aging of blood stem cells. Understanding these changes not only informs how we protect astronauts during long-duration missions but also helps us model human aging and diseases like cancer here on Earth. This is essential knowledge as we enter a new era of commercial space travel and research in low earth orbit.”

Jamieson is senior author of the team’s published paper in Cell Stem Cell. In their report, titled “Nanobioreactor detection of space-associated hematopoietic stem and progenitor cell aging,” the team concluded, “These short-duration spaceflight models of accelerated HSPC aging may provide insights into terrestrial human aging and age-related malignancies.

Previous NASA studies have shown that spaceflight can affect immune function and telomere length. “In the stressful environment of low-earth orbit (LEO), which has been increasingly used for scientific discovery and commercial manufacturing, fundamental physical phenomena shift, leading to changes in immune function, metabolic processes, and other physiological responses,” the authors explained.

One such study—the NASA Twins Study—was a landmark, year-long experiment (2015-2016) where astronaut Scott Kelly spent 340 days aboard the ISS while his identical twin, Mark Kelly, remained on Earth. The study tracked changes across genetics, physiology, cognition, and the microbiome and found altered gene expression, shifts in telomere length, and changes in the gut microbiome.

However, many of these changes reversed or returned to normal after astronaut Kelly returned to Earth. The study did identify some persistent changes, such as increased numbers of short telomeres and disruptions in gene expression, which could be relevant for longer space missions.

The newly reported UC San Diego-led study builds on the findings of the Twins Study and the seminal work of the Space Omics and Medical Atlas group, which published 44 scientific papers on aerospace medicine and space biology in Nature.

By focusing specifically on HSPCs, the study in Cell Stem Cell offers a detailed mechanistic look at how space triggers molecular aging, something the Twins Study hinted at but could not fully explore at the cellular level. “Few studies have investigated the combined stressors associated with the extreme environment of space on functional processes regulated at the HSPC level that will be vital for understanding the human-specific limitations of long-duration spaceflight,” Jameison and team noted.
To conduct their study, the researchers, including a team at Space Tango, developed a novel “nanobioreactor” platform—miniaturized 3D biosensing systems that allowed human stem cells to be cultured in space and monitored with AI-powered imaging tools. “To determine whether HSPC fitness is impaired and immune dysfunction derives from the loss of normal HSPC homeostasis in space compared with terrestrial environments, we developed a 3D biosensing nanobioreactor system that enables prolonged maintenance of human HSPCs,” they explained.

Their results showed that human HSPCs exposed to 32 to 45 days of spaceflight showed hallmark features of aging. Spaceflight was found to trigger a range of changes in blood-forming stem cells that closely resemble what happens to these cells as we age. The cells became more active than normal, burning through their reserves and losing the ability to rest and recover—a key trait that allows stem cells to regenerate over time.

The results showed that the ability of HSPCs in space to make healthy new cells declined, while signs of molecular wear-and-tear, such as DNA damage and shorter chromosome ends—telomeres—became more pronounced.

The cells also showed signs of inflammation and stress inside their mitochondria and began activating hidden sections of the genome that are normally kept quiet to maintain stability. These stress responses can impair immune function and increase the risk of diseases.

“…we observed inflammatory cytokine changes, mitochondrial DNA amplification, protein translation, and mitochondrial gene expression changes, which corroborated previous studies showing inflammatory cytokine and mitochondrial deregulation in longer-duration spaceflight,” the scientists reported.

“Together, these findings suggest a diminished capacity of HSPCs to maintain their function upon return from spaceflight, which is consistent with accelerated stem cell aging.”

Notably, when these space-exposed cells were later placed in a young, healthy environment, some of the damage began to reverse, suggesting it may be possible to rejuvenate aging cells with the right interventions. “Space-associated HSPC aging can be partially reversed on young stroma,” the scientists further stated.

“We’re excited this breakthrough work is being published to the wider scientific and space communities,” said Twyman Clements, president and co-founder of Space Tango. “Like many accomplishments, this one was a team effort bringing together the Integrated Space Stem Cell Orbital Research Center within SSCI, Space Tango, and others. Coupling Space Tango’s CubeLab capabilities, specifically the persistent microscopy, has enabled this work and will continue to do so in the future.”

The research team plans to extend their work with additional ISS missions and astronaut-based studies, focusing on real-time monitoring of molecular changes and potential pharmaceutical or genetic countermeasures to protect human health in space and beyond. To date, the SSCI has conducted 17 missions to the ISS.

The authors stated, “Together, our results reveal spaceflight-associated HSPC aging, thereby setting the stage for the development of countermeasures to enable long-duration human spaceflight and establish AI-driven technologies for predicting HSPC functional decline under conditions of macroenvironmental stress in space and terrestrially…Ultimately, these studies may provide guidance for therapeutic strategies to mitigate space-specific changes in the expanding space economy, as well as space-accelerated models of aging and age-related diseases, such as cancer.”

“Space experiments are so complex that they force you to do better science on the ground,” continued Jamieson. “Space research has accelerated technological advancements on Earth, making ground-based research easier and more relevant to human health. What we have learned about cancer from our studies in space is absolutely remarkable.”

In their paper the researchers suggested, “Moreover, the methods and findings from our study can help facilitate future studies to predict and understand the observed molecular changes for longer-duration or further destination spaceflight missions.”

Ionis Pharmaceuticals (NASDAQ: IONS) shares surged nearly 44% this past week after the developer of RNA-targeted therapies came out with positive data from two pivotal Phase III trials assessing a potential new indication for olezarsen as a treatment for severe hypertriglyceridemia (sHTG).

Olezarsen is an antisense oligonucleotide designed to lower the body’s production of apolipoprotein-CIII (apoC-III), a protein produced in the liver that regulates triglyceride metabolism in the blood. Olezarsen is already marketed in the United States, where it is the first FDA-approved treatment, as an adjunct to diet, to reduce triglycerides in patients with familial chylomicronemia (FCS) under the brand name Tryngolza®.

On September 2, Ionis said the 617-patient CORE trial (NCT05079919) and 446-patient CORE2 trial (NCT05552326) met its primary endpoint by showing an up to 72% placebo-adjusted mean reduction in fasting triglycerides at six months compared to placebo, as well as an 85% reduction in acute pancreatitis events with favorable safety and tolerability—results that Ionis has termed “highly statistically significant.”

“We believe these unprecedented results position olezarsen to meet the substantial unmet needs of people with sHTG, a patient population in great need for more effective triglyceride-lowering treatments to reduce the risk of potentially fatal acute pancreatitis,” Ionis founder and CEO Brett P. Monia, PhD, told analysts on a conference call.

Ionis plans to present detailed data at an upcoming medical conference, file a supplemental New Drug Application (sNDA) with the FDA for olezarsen in sHTG by year’s end, and if approved, launch the drug in that indication in 2026. Olezarsen is one of two launches the company is planning for next year. The other is Zilganersen, a potential first disease-modifying treatment for people with Alexander disease.

Ionis has not publicly estimated how much revenue it expects to generate from an sHTG indication for olezarsen, though Monia and other company executives have said that the drug has the potential to be a blockbuster, which is what industry calls drugs with sales of more than $1 billion.

“Based on this data, based on the patient population that’s addressable that we were talking about previously of greater than one million patients that have high-risk sHTG, we believe that we’ll be able to work effectively with these specialists and get them on olezarsen quickly and realize the blockbuster potential that this represents,” Kyle Jenne, Ionis’ executive vp and chief global product strategy officer, said on the analyst call.

Buying surge

The talk of blockbuster sales, plus positive CORE and CORE2 data, wowed investors enough to touch off a buying surge that sent Ionis shares soaring over two days.

From a close of $42.64 on August 29, Ionis shares jumped 35% to $57.49 on September 2, then rose another 5% to $60.49 on Wednesday, after reaching a 52-week high of $62.08 earlier that day. The stock dipped 2% Thursday to $59.35 on apparent profit-taking, but bounced back 3% Friday, finishing the week at $61.23.

Akash Tewari, global head of biopharmaceutical research and an equity analyst with Jefferies, wrote in a research note that his firm has raised its peak-year sales forecast for olezarsen 67%, from $1.5 billion to $2.5 billion, reasoning that the drug will reach more patients with sHTG as a result of the strong Phase III data. Tewari also raised his firm’s 12-month price target on Ionis shares 16% from $83 to $96, maintaining a “Buy” rating.

That’s a far cry from the $26 million in sales generated by Tryngolza during the first half of this year, most of which ($19 million) came during the second quarter. The drug was granted FDA approval in December 2024.

Jefferies forecasts olezarsen penetration reaching 13% of patients with triglyceride levels of greater than 880 mg/dL, a level classified as being sHTG; as well as 50% of sHTG patients with TG levels of 500–880 mg/dL with acute pancreatitis (AP) history; but only 1% of patients with TG levels above 500 mg/dL with no AP history.

“We think our penetration assumptions are still conservative,” Tewari said. “There could be further upside depending on pricing & pt adoption. Given the strong AP data, we think IONS could potentially get the pricing to the upper end of $10–20K net price range that mgmt. [management] had previously disclosed.”

Price question

On the call, Jenne deflected a question from Tewari about whether Ionis planned to raise its price for olezarsen in sHTG as a result of the data: “We’ll announce the price at the approval of the sHTG indication. And as I stated, it will reflect the value of olezarsen in that patient population.”

Tewari wasn’t alone in his upbeat outlook on Ionis shares.

“Taken together, we view these data as a best-case scenario for Ionis,” Myles R. Minter, PhD, a partner and biotechnology analyst with William Blair, wrote in a research note.

Beyond olezarsen, Minter added, “We view today’s top-line data as clinical validation for ApoC-III lowering in sHTG, particularly its effectiveness in lowering pancreatitis events.”

That validation will read through, Minter predicted, to other apoC-III silencers—both small interfering RNA candidates, such as plozasiran from Arrowhead Pharmaceuticals (NASDAQ: ARWR) and ALN-APOC3 from Alnylam Pharmaceuticals (NASDAQ: ALNY), as well as gene editing-based assets in lead optimization phases from two privately held therapeutics developers—MB-111 from Mammoth Biosciences and STX1400 from Scribe Therapeutics.

“Olezarsen’s statistically significant effect on AP [acute pancreatitis] positions IONS for a blockbuster 2H26 launch in sHTG,” BMO Capital Markets analyst Kostas Biliouris wrote in a research note, as reported by Seeking Alpha.

Biliouris upgraded his firm’s rating of the stock from “Market Perform” to “Outperform” and raised BMO’s 12-month price target on Ionis shares 75%, from $40 to $70. Numerous other analysts joined Biliouris and Tewari in raising their price targets on Ionis, including:

H. Wainwright (Mitchell Kapoor)—Up 36% from $70 to $95, maintaining a “Buy” rating.

Barclays (Gena Wang, PhD)—Up 34% from $58 to $78, maintaining an “Overweight” rating.

Needham & Co. (Joseph Stringer, PhD)—Up 27% from $55 to $70, maintaining a “Buy” rating.

Citigroup (David Lebowitz)—Up 22% from $69 to $84, maintaining a “Buy” rating.

Morgan Stanley (Michael Ulz)—Up 14.5% from $62 to $71, maintaining an “Overweight” rating.

RBC Capital Markets (Luca Issi, PhD)—Up 14% from $70 to $80, maintaining an “Outperform” rating.

Leerink Partners (Mani Foroohar, MD)—Up 14% from $56 to $64, maintaining an “Outperform” rating.

Goldman Sachs (Salveen Richter)—Up 12.5% from $40 to $45, maintaining a “Sell” rating.

Pressure on Arrowhead

Foroohar said Ionis’ success with olezarsen increases pressure on Arrowhead to succeed with plozasiran (ARO-APOC3), an RNA interference (RNAi) therapeutic that, like olezarsen, is designed to treat sHTG by reducing production of apoC-III.

Plozasiran is under study for sHTG in three Phase III trials that have all completed patient enrollment—SHASTA-3 (NCT06347003), SHASTA-4 (NCT06347016), and MUIR-3 (NCT06347133). In reporting results for the third quarter of its 2025 fiscal year last month, Arrowhead said it anticipated completing the primary portion of the trials in mid-2026 with topline data expected shortly thereafter, to be followed by regulatory submissions for review.

“For competitor ARWR, CORE data makes clinical differentiation an uphill battle (favoring IONS’ first-mover advantage),” Foroohar observed, adding that the CORE and CORE2 data “shifts the onus on ARWR to execute clinically and commercially to keep pace with IONS.”

Plozasiran is also under FDA review in FCS, for which Arrowhead has submitted a New Drug Application (NDA) based on positive data from the Phase III PALISADE trial (NCT05089084). The FDA has set a target action date of November 18 for plozasiran in FCS under the Prescription Drug User Fee Act (PDUFA).

Following Ionis’ announcement, Arrowhead also saw its stock jump nearly 17%, from $22.03 to $25.68—though the increase reflected more Novartis agreeing to license and develop Arrowhead’s ARO-SNCA, a preclinical stage small interfering RNA (siRNA) therapy candidate for Parkinson’s disease and other synucleinopathies, plus additional targets. The collaboration could generate more than $2.2 billion for Arrowhead, an RNAi-based drug developer based in Pasadena, CA.

Leaders and laggards

Cybin (NYSE American: CYBN) shares slumped nearly 17% from $7.48 to $6.24 on September 2 after the psychedelic drug developer’s CEO Doug Drysdale stepped down effective that day. Cybin’s board has appointed co-founder and executive chairman Eric So as interim CEO and established a committee to conduct a search for a permanent CEO. “I look forward to executing on our strategy, advancing our clinical pipeline to successful approval of CYB003 and CYB004, and working closely with our partners as we move toward delivering innovative new therapies for patients in need,” So stated. CYB003 is a deuterated psilocin analog in Phase III studies for adjunctive treatment of major depressive disorder, while CYB004 is a deuterated N, N-dimethyltryptamine molecule in a Phase II study for generalized anxiety disorder.

Mineralys (NASDAQ: MLYS) shares rocketed 86% Tuesday, from $15.48 to $28.86, as the company benefited from positive Phase III data published in the New England Journal of Medicine by AstraZeneca (London: AZN) for baxdrostat, a blood pressure treatment with a similar mechanism to Mineralys’ lead candidate lorundrostat. AstraZeneca reported that baxdrostat showed statistically significant and clinically meaningful reduction in systolic blood pressure in patients with hard-to-control hypertension in the BaxHTN trial (NCT06034743). Baxdrostat 2 mg lowered systolic blood pressure by 15.7 mmHg (9.8 mmHg placebo-adjusted) from baseline. AstraZeneca shares rose 3% over two days, from 11,850 pence Monday to 12,210 pence Wednesday, on the positive baxdrostat news. After the close of trading Tuesday, Mineralys priced an upsized $350 million underwritten public offering of 9,803,921 shares at $25.50 per share.

New FDA expert panels, such as recent meetings on SSRI use during pregnancy and on hormone replacement therapy during menopause, are drawing criticism for being one-sided. One leader says such panels are designed to reach a specific conclusion.

Earlier this summer, the FDA convened an expert panel to weigh the benefits and risks introduced by selective serotonin reuptake inhibitor use during pregnancy. However, the discussion immediately drew controversy due to the near unanimity of panelists critical of SSRIs, with 9 of the 10 experts presenting information that highlighted the potential risks of using the medication during pregnancy.

The FDA’s expert panels—the first of which took place in May—are a new format for the agency during which an “independent panel of scientific experts” will “review the latest scientific evidence, evaluate potential health risks, explore safer alternatives” and possibly offer recommendations for regulatory action.

Another such panel, held a week prior to the SSRI discussion, focused on menopause and hormone replacement therapy (HRT). As with the SSRI discussion, the panel faced criticism over apparent bias, with an overwhelming majority in favor of removing black box warnings for this type of treatment. Diana Zuckerman, president of the nonprofit National Center for Health Research, was struck by the lack of nuance presented during these panels.

“For SSRIs and for hormone therapy, two of the expert panels where I know the issues the best, these are areas with some nuance—you could have panelists who have a diversity of opinion,” she told BioSpace. “What I was most surprised by is how they didn’t do that. They didn’t want any nuance. It seemed they didn’t want any real difference of opinion.

A Lack of Balance

FDA Commissioner Marty Makary opened the expert panel on SSRIs and pregnancy by highlighting how the U.S. is “losing the broader battle” against mental health issues. Makary stressed the potential of alternative means, such as healthy relationships, communities and natural light exposure, to address the situation, before moving on to list the possible risks that SSRIs pose in pregnancy. His statement did not include any mention of the potential benefits of the drugs or the risks created by not taking them.

Mental health disorders pose significant risks for women in the perinatal period, accounting for 5%–20% of maternal deaths in high-income countries.

In the panel discussion that followed, nine participants highlighted the potential negative impacts of SSRIs on the fetus, including increased risk of congenital malformations, prematurity and low birth weight. Some panelists proposed adding a black box warning to the drugs’ labels for use during pregnancy. Only one participant, Kay Roussos-Ross, director of the perinatal mood disorders program at the University of Florida, covered the risks posed to pregnant women by not taking SSRIs to manage depressive symptoms.

“We should be having these regular discussions and reviewing the safety,” Christine Crawford, associate medical director at the National Alliance on Mental Illness (NAMI), told BioSpace. “I also encourage people to keep in mind that, yes, there are data to suggest there might be some issues related to being on an SSRI for the baby, such as persistent pulmonary hypertension. However,” she cautioned, “The likelihood of that happening is far, far, far less likely than someone becoming suicidal while pregnant, if they don’t take SSRIs or stop taking them.”

Christopher Zahn, chief of clinical practice at the American College of Obstetricians and Gynecologists (ACOG), concurred. In an email to BioSpace, he said that pregnant patients need to understand the risks of taking SSRIs, but added that it is also “critically important” they understand the dangers posed by not treating or under-treating their condition. “This concept is sometimes lost in the current environment around the FDA panel discussions,” Zahn said.

Limited Public Access

The FDA’s advisory committees—which have been in place since the 1970s and consist of an independent panel of experts who advise the agency on scientific, medical and regulatory issues, including the potential approval of new drugs and medical devices—are the closest parallel to the new expert panels.

Steven Grossman, policy and regulatory consultant and author of the FDA Matters blog, observed a difference in the makeup of the two formats. “Although from time to time there are accusations that an advisory committee was tilted to one side—even in those cases, it would be subtle and usually involve questions about one or two people, not almost the entire panel,” he told BioSpace in an email.

Zuckerman added that, in her experience, the panels appear to be less inviting to the public than traditional adcomms. The HRT panel Zuckerman attended was held in a much smaller room than is typical for an advisory committee. She noted that this was despite the fact that another adcomm meeting had just concluded, opening up a much larger space. The smaller room quickly filled up, she recalled, and people were turned away. There was also no opportunity for public comment.

Furthermore, the expert panels offered a shorter window for people to sign up to attend, Zuckerman said—less than a week—when compared with advisory committee meetings, which often have a period of three to five weeks to register.

Zuckerman was unfamiliar with many of the attendees, which she noted was unusual for a field in which she had worked for a number of years. This suggested that the audience, at least partially, was made up of invitees of the panelists, she said.

Confirmation Bias

For Zuckerman, the expert panels seem to be designed both to influence public opinion on the topic and also to send a message to industry: “This is the direction we’re going in. Feel free to push us in that direction.”

When asked about the purpose of the expert panels, a Health and Human Services (HHS) spokesperson told BioSpace in an email that “Commissioner Makary has an interest in ensuring policies reflect the latest gold standard science and protect public health.”

For industry, the results of the recent panels are varied. Removing black box warnings from HRT would be a clear opportunity for industry to benefit from increased sales of such products by reducing safety concerns, Zuckerman said. Conversely, adding a black box warning to SSRIs would likely be detrimental to industry sales—though with many of these products being off-patent, they are no longer especially lucrative.

Grossman suggested that the FDA’s focus on SSRIs could simply be a specific concern for Health Secretary Robert F. Kennedy Jr., Makary or even one of their associates. He added that strong pushback on SSRIs and mental health drugs, in general, has always existed.

If a black box warning were to be added to SSRIs in this context, Crawford said this would pose an even bigger barrier to the adoption of the medication by people with mental health disorders, particularly as pregnancy is a period when people are already likely to be anxious about their health.

“We’ve been through this before when the FDA had the black box warning on SSRIs for young people,” Crawford said. “We saw the number of prescriptions for SSRIs plummet and then rates of depression and suicide went up.”

When asked about how the FDA would interpret the conclusions from the panel, the HHS spokesperson said they would not comment on any potential future policy decisions.

Amid an unprecedented turnover in leadership at the FDA and mass layoffs of staff, communication has crumbled and uncertainty runs rampant, leaving small and medium biopharma companies without a clear path forward for their therapies.

Change is hard—especially when a new administration comes in gung-ho to overhaul the entire system. For Health Secretary Robert F. Kennedy Jr., this has meant slashing some 10,000 jobs at the Department of Health and Human Services and overseeing an extensive turnover of leadership at the highest levels. At the FDA, Commissioner Marty Makary has announced plans to speed drug reviews through avenues such as the Commissioner’s National Priority Voucher, expedite rare disease therapies through a yet-to-be-defined conditional approval pathway and ban pharmaceutical representatives from some advisory committees.

With all this upheaval, many biopharma companies have gotten caught up in the confusion. Ironically, many of them are seeking approval for rare disease therapies.

Capricor Therapeutics, Ultragenyx and Replimune have expressed surprise at recent rejections in Duchenne muscular dystrophy (DMD) cardiomyopathy, Sanfilippo syndrome type A and melanoma, respectively. Meanwhile, three deaths stemming from Sarepta’s gene therapy platform—two of which were associated with its DMD therapy Elevidys—prompted the FDA to request the company halt all shipments of the approved therapy.

Amidst these developments, Center for Biologics Evaluation and Research Director Vinay Prasad suddenly left his role, only to return less than two weeks later. With rumors swirling of his direct involvement in some regulatory decisions, his temporary ouster only adds to the uncertainty some biotechs are facing.

“These companies who don’t have a lot of cash at hand, they’re actually looking to create these treatments for rare diseases,” Rahul Gupta, president of AI/ML company GATC Health, who served as head of the White House Office of National Drug Control Policy under former President Joe Biden, told BioSpace. “They need a very clear framework, a blueprint of what’s acceptable, what’s not acceptable, and how things will go so they’re not feeling like they’re gambling with their limited amount of funds every time they go up to the FDA.”

Here, BioSpace unpacks the journeys of five biotechs that have tangled with the new FDA over the past six months.

Sarepta’s Summer Saga

Like it or not, the biopharma story of the summer belongs to Sarepta Therapeutics. The Massachusetts-based biotech had a difficult spring, with two nonambulatory teenage patients taking Elevidys succumbing to acute liver injury. It appeared that Sarepta was managing the risks, adding a black box warning to Elevidys’ label for acute liver injury and acute liver failure.

But after the death of a third patient—a 51-year-old nonambultory man who had been participating in a Phase I study of Sarepta’s SRP-9004 for limb-girdle muscular dystrophy (LGMD), which used the same underlying technology as Elevidys—the FDA acted, requesting that Sarepta stop all shipments of the gene therapy in the U.S. and pause all LGMD clinical trials. The agency also revoked the platform designation the biotech had previously been granted for its viral vector technology.

Initially, Sarepta stood its ground, refusing the FDA’s request. Notably, in its July 18 statement, the company said, “We first heard of this potential request earlier in the day at the same time the public and our patient communities did, through media reports.” The company noted in the same press release that it had alerted the FDA to the death on July 3. The agency later confirmed this to be true but told STAT News that the report had been lost in the bureaucracy and that it had, in fact, only learned of the death with the rest of the world when BioCentury reported it. The FDA further stated it had always planned to take action if a third death occurred.

Sarepta ultimately relented to the FDA’s request to halt Elevidys shipments, setting off a week of action for patient groups eager to regain access to the treatment. That action apparently worked. On July 28, the FDA did a 180 and recommended that the voluntary hold on Elevidys be lifted for ambulatory patients. The following day, Prasad was out as CBER director—a development multiple sources suggested was connected to the Sarepta saga.

The “unprecedented” FDA leaks were “missteps” on the part of CBER that sowed confusion for both Sarepta and patients, BMO Capital Markets’ Kostas Biliouris wrote to investors on July 30.

Capricor Communication Kerfluffle

Capricor has also reportedly been caught on the carousel of FDA change. The rejection of the company’s cell therapy deramiocel in July “was unexpected given the trajectory of positive [FDA] interactions,” CEO Linda Marbán said during the company’s second-quarter earnings call on Aug. 11.

Drama reportedly predated the rejection, however.

Nicole Verdun, the former director of the FDA’s Office of Therapeutic Products, and her deputy, Rachael Anatol, were allegedly “put on administrative leave because of an argument about our file, and that Prasad wanted to [reject] us and Nicole was fighting it,” Marbán told BioSpace in an earlier interview, attributing the information to a STAT reporter who’d contacted her after receiving a tip from an agency insider.

After Prasad stepped aside from his role on July 29, Marbán expressed optimism about the company’s chances of fighting the rejection. Speaking again with BioSpace after his return less than 10 days later, she said: “My initial reaction was of great surprise. It was pretty clear that he was asked to leave . . . but I think what it showed is that Makary has tremendous faith in him. We all understand the ramifications of that, that there’s not a lot of ladders you can go up besides the Prasad ladder.”

Nevertheless, Capricor is full speed ahead with its resubmission plans for deramiocel. The biotech met with the FDA on Aug. 13 for a type A meeting to discuss a path forward, but Marbán said she would appreciate an audience with Prasad, who did not attend the meeting.

“We’ve never had any direct communication from or with him. We would like that very much, but nothing so far.”

Ultragenyx’s Unread Responses

Also on July 11, the FDA declined to approve Ultragenyx’s investigational in vivo gene therapy UX111, which the biotech is proposing for Sanfilippo syndrome type A—an ultrarare disease that leads to neurological symptoms including language and developmental delays and progressive intellectual disability.

On the July 17 edition of STAT News’ podcast, The Readout Loud, Ultragenyx CEO Emil Kakkis said that a number of issues were raised during the CMC inspection process, which the company was in the process of addressing. Ultragenyx had sent the FDA “a number of very large responses,” Kakkis said. However, at the time of the complete response letter (CRL), “they hadn’t actually read or completed review of the last four responses we had given them. They issued the CRL before they had fully reviewed those responses.”

Ultragenyx “believes that these [CMC] observations are readily addressable and many have already been addressed,” Kakkis said in a prepared statement on July 11. Ultragenyx plans to resubmit an approval application and anticipates another six-month review period for UX111.

Replimune’s Surprise Rejection

In contrast to the other three companies on this list, Replimune can apparently thank a legacy FDA leader for the rejection of its candidate. According to reporting by multiple news outlets, Richard Pazdur, director of the FDA’s Oncology Center of Excellence (OCE) and acting director of the Office of Oncologic Diseases, directly intervened to issue the CRL for Replimune’s advanced melanoma drug, RP1. Pazdur has been the agency’s chief cancer strategist for more than 25 years.

An unnamed FDA official told STAT News on Aug. 4 that CBER “mishandled the RP1 review from the beginning,” compelling Pazdur and his team to get involved. The situation was exacerbated, the individual added, by the leadership upheaval within CBER.

In Replimune’s announcement of the CRL, CEO Sushil Patel expressed surprise with the decision.

“The issues highlighted in the CRL were not raised by the agency during the mid- and late-cycle reviews,” he said in a prepared statement. “Additionally, we had also aligned on the design of the confirmatory study. We strongly believe that RP1 in combination with nivolumab [Bristol Myers Squibb’s Opdivo] can bring substantial benefit to advanced melanoma patients.”

On Aug. 5, 22 experts who designed and ran RP1’s Phase III trial issued an open letter responding to several issues outlined in the CRL and urging the FDA to “re-review” Replimune’s application.

This decision has had further reverberations as well. Late last month, Krystal Biotech discontinued a Phase I/II study of its investigational intratumoral therapy KB707, which it is developing for solid tumors. Speaking with STAT, Stéphane Paquette, Krystal’s vice president for corporate development, said “heightened uncertainty regarding potential accelerated approval pathways” for KB707 following the FDA’s rejection of RP1 contributed to the biotech’s decision.

Novavax’s Delay

When the FDA missed its deadline to issue a decision regarding the 2024–2025 formulation of Novavax’s COVID-19 vaccine on April 1, concern circulated about what it could mean for the broader vaccines space. While the Maryland-based company did ultimately secure a narrow nod for Nuvaxovid, the approval process represented a potential “harbinger” of a threat to the FDA’s integrity, former FDA associate commissioner Peter Lurie told BioSpace in June.

On April 2, Politico reported that deputy FDA commissioner Sara Brenner directly intervened in the review of Novavax’s vaccine application. A few days later, Kennedy said the delay reflected HHS’ “shifting [its] priorities to multiple-antigen vaccines,” causing the company’s shares to drop by 24%. The influence of both Brenner and Kennedy is a significant deviation from normal protocols, Lurie and three other former government officials wrote in an op-ed published in the Journal of the American Medical Association in June.

On May 16, the FDA approved Nuvaxovid for all seniors aged 65 years and older and people 12 through 64 years of age at high risk for severe outcomes from COVID-19. Similar restrictions have now also been applied to the three other vaccines marketed in the U.S.—Pfizer and BioNTech’s Comirnaty and Moderna’s Spikevax and mNEXSPIKE—in line with the FDA’s new risk-based approach to COVID-19 vaccination introduced in May.

Rick Doblin, the founder of the Multidisciplinary Association for Psychedelic Studies, which founded Lykos, bemoaned a “moving of the goal posts” in Lykos’ rejection but looked for positives in the newly released complete response letter.

Lykos Therapeutics founder Rick Doblin has something to say now that the public can see the FDA letter that shot down the company’s midomafetamine (MDMA)-assisted therapy for post-traumatic stress disorder in August 2024.

The FDA’s rejection of Lykos’ drug at the time did not come as a shock. The complete response letter (CRL) arrived after an advisory committee meeting voted 10-1 against recommending approval.

But now, after the FDA released another cache of rejection letters, the agency’s specific objections have been entered into the public domain. For Lykos, which re-branded itself last week as Resilient Therapeutics, those concerns include unreported safety events at two different sites, as well as abuse of the drugs, their duration of effect, study design and the number of patients who had previously reported using MDMA.

For example, in the CRL to Lykos, the FDA said that the company had not demonstrated that the drug’s effect was durable past an 18 week end-of-study assessment, which came eight weeks after the last dose of the drug.

“Now that the CRL is public I’ve got some comments about it,” Doblin said during a Friday press conference to discuss the public release of Lykos’ CRL. “There is a changing of the goal posts.”

Doblin—who also founded Multidisciplinary Association for Psychedelic Studies (MAPS), the organization that initially founded Lykos—went on to detail a long history of Lykos and midomafetamine’s development history. In particular, he noted that between the time the advisory committee nearly unanimously voted to not recommend Lykos’ drug and the actual decision by the FDA to reject the drug, Lykos submitted an amendment to the new drug application for the therapy addressing the agency’s concerns.

Doblin quoted the newly released CRL directly: “We also acknowledge the receipt of your amendment dated, and then the date is blocked out, which was not reviewed for this action.”

The amendment was submitted by Lykos, according to Doblin, to address many of the issues raised by the advisory committee, which focused on efficacy and durability of response demonstrated in Lykos’ data, before the FDA rendered its decision.

“Those responses from the company were not considered in this complete response letter,” Doblin said.

Meanwhile, durability of response has never been a condition of FDA approval, Doblin contended, pointing to the durability of many cancer drugs, where relapses after treatment may be common. He also pointed to Johnson & Johnson’s esketamine therapeutic Spravato, approved for major depressive disorder and treatment-resistant depression.

“Results fade pretty quickly with Spravato,” Doblin said. The therapy was approved based partially on data showing duration of response through at least 32 weeks.

Doblin also addressed part of the FDA’s CRL that recommended a new randomized, double-blind study to address durability of effect.

“The issue of how to do a double-blind study is very complicated,” Doblin said, stating that discussions of how to conduct such a trial delayed Lykos’ moving to Phase III by eight months. Part of the issue, according to Doblin, is that it’s difficult to blind a study for a drug that has at least a partially psychedelic effect on participants.

“The FDA said that often in practice, the double blind fails to work anyway, even with SSRIs,” where significant side effects can tip a patient off on whether they received an active ingredient or a placebo, Doblin said. He also pointed out that Spravato was approved based only on single-blind studies.

Doblin said that MAPS is talking directly to the Trump administration but did not provide details. “MAPS is now engaged in discussions with people in the administration, not in the FDA, about whether we already have an evidence-based therapy,” citing 25 years of what he called “interdirected therapies,” without specifying what those were or what those discussions entailed.

At the end of the day, however, Doblin sees a light at the end of the tunnel for psychedelic therapies. “I am so relieved that the FDA released this CRL,” he said. “The for-profit psychedelic industry has got the wrong message.” According to Doblin, the message received by psychedelic drug companies is that psychotherapy is a problem and that they should try to minimize the role of it in mental health, instead focusing on therapeutics.

“‘Don’t do any therapy. Try to be just drug companies,’” Doblin described of the erroneous message. Instead, he insisted, “the field should get the idea that it’s about what’s best for patients.”

Robert F. Kennedy Jr. repeated a series of anti-vaccine talking points during his appearance in front of the Senate finance committee on Thursday, as Democratic and Republican senators alike hammered the Health Secretary on recent COVID-19 vaccine restrictions and his views on Operation Warp Speed.
Robert F. Kennedy Jr.’s testimony in front of the Senate finance committee on Thursday often rose to the level of shouting, as senators from both sides of the aisle accused the country’s health secretary of reneging on promises he had made during his confirmation hearings to maintain access to vaccines.

The hearing came a week after the FDA granted restricted approvals for COVID-19 vaccines developed by Pfizer/BioNTech, Moderna and Novavax for adults 65 and older and younger people at elevated risk of severe disease. This has thrown the country into considerable confusion, with CVS announcing Monday that it will not offer COVID-19 shots in 16 states. During her allotted time at Thursday’s meeting, Sen. Elizabeth Warren (D-MA) went around in circles with Kennedy on the question of access.

“There was clearly deep unhappiness with the secretary’s responses, from senators on both sides of the aisle for going back on his word,” Dorit Reiss, professor of law at UC Law San Francisco, told BioSpace.

During the hearing, Kennedy repeatedly stated that COVID-19 vaccines were harmful or hadn’t been adequately tested, which raised objections from several senators on the committee.

“We were lied to,” Kennedy alleged at one point about the effectiveness of mRNA-based COVID-19 vaccines that were developed under Operation Warp Speed during President Donald Trump’s first term. Without providing evidence, the secretary said that the vaccines’ effectiveness was only tested in animals.

The safety and efficacy of both Pfizer/BioNTech’s and Moderna’s vaccines were tested in human clinical trials.

“I’m a doctor. Vaccines work,” Sen. John Barrasso (R-WY) said during the hearing.

Kennedy pushed back on accusations levied by several senators that he is anti-vaccine. “Saying I’m anti-vaccine is like saying I’m anti-medicine,” he said Thursday, according to NPR. “It doesn’t mean that I’m, you know, anti-vax. It just means I’m pro-science.”

Reiss wasn’t sold. “In spite of saying he’s not, he’s clearly anti-vaccine,” she said, adding that Kennedy repeated several anti-vaccine talking points, including claiming that COVID-19 vaccines carry substantial risks and death rates and that they have not been adequately studied. “All this is untrue, are anti-vaccine tropes and are ill-founded.”

Thursday’s hearing followed a series of high-profile shake-ups at the CDC, including the firing of newly confirmed director Susan Monarez and the resignation of three other high-ranking regulators. In an op-ed Thursday in The Wall Street Journal, Monarez alleged that she was fired for refusing to pre-approve recommendations made by the CDC’s Advisory Committee on Immunization Practices. Presented with the editorial during the hearing, Kennedy refuted Monarez’s claims, saying she was lying.

Political Theater

“As political theater goes, it was a great hearing,” Steven Grossman, policy analyst and author of the FDA Matters blog, told BioSpace. “It turned heavily on Kennedy’s stubborn self-assurance and unwillingness to depart even an iota from his well-rehearsed script. As a rule, actual shouting matches are rare, but there were several.”

A notable example occurred when Kennedy stated that medical associations that have pushed back against his policies, like the American Heart Association, are corrupt or in debt to the pharmaceutical industry. Sen. Bernie Sanders (I-VT), voice raised, said that Kennedy essentially believed anyone who opposed him was corrupt.

Kennedy has been under increasing pressure from Sanders and others since Monarez’s firing. A group of former CDC directors and acting directors have levied heavy criticism on the secretary, while Sanders called for his firing in an editorial published Aug. 30 in The New York Times. The largest voice came in the form of an open letter, published this week, from over 1,000 current and former Health and Human Services employees, also calling for Kennedy to resign.

“Typically, federal employees are very quiet about anything political. They don’t comment,” Paul Offit, director of the Vaccine Education Center at the Children’s Hospital of Philadelphia, told BioSpace. “It tells you how angry people are right now, and it also tells you that the Trump administration is missing this, because the people like vaccines. Most parents embrace vaccines.”

Whether Kennedy might meet his end at HHS anytime soon is unclear. Reiss speculated that part of the political theater to which Grossman referred was an attempt to influence the president’s thinking on this matter.

“Several Republican senators mentioned Operation Warp Speed, and I think that was reminding the president his role in this important operation,” she said—“and maybe to get Trump to fire Kennedy. That’s why they kept bringing it up.”

For Offit, however, theater is pretty much the only takeaway from Thursday’s hearing. “I think that this committee hearing is largely a chance for senators to vent and will accomplish nothing,” he said. Ultimately, he continued, Republican congresspeople need to march into Trump’s office and tell the president that “‘they’re scared they’re going to lose vaccines.’”

“Trump wants to do grand things, and I think he thinks Kennedy can do that.”

Researchers from University of California San Diego Sanford Stem Cell Institute have discovered that spaceflight accelerates the aging of human hematopoietic stem and progenitor cells (HSPCs), which are vital for blood and immune system health.

The team used automated artificial intelligence (AI)-driven stem cell-tracking nanobioreactor systems to track stem cell changes in real time, during four SpaceX Commercial Resupply Services missions to the International Space Station (ISS). The findings showed that the cells lost some of their ability to make healthy new cells, became more prone to DNA damage, and showed signs of faster aging at the ends of their chromosomes after spaceflight—all signs of accelerated aging.

The findings have implications not just for astronaut health, but also for understanding the mechanisms of aging and age-related diseases, such as cancer, on Earth. The results also underscore the need for new countermeasures to protect stem cell function during extended space missions and support the development of biological markers to detect stress-induced aging early.

“Space is the ultimate stress test for the human body,” said research lead Catriona Jamieson, MD, PhD, director of the Sanford Stem Cell Institute and professor of medicine at UC San Diego School of Medicine. “These findings are critically important because they show that the stressors of space—like microgravity and cosmic galactic radiation—can accelerate the molecular aging of blood stem cells. Understanding these changes not only informs how we protect astronauts during long-duration missions but also helps us model human aging and diseases like cancer here on Earth. This is essential knowledge as we enter a new era of commercial space travel and research in low earth orbit.”

Jamieson is senior author of the team’s published paper in Cell Stem Cell. In their report, titled “Nanobioreactor detection of space-associated hematopoietic stem and progenitor cell aging,” the team concluded, “These short-duration spaceflight models of accelerated HSPC aging may provide insights into terrestrial human aging and age-related malignancies.

Previous NASA studies have shown that spaceflight can affect immune function and telomere length. “In the stressful environment of low-earth orbit (LEO), which has been increasingly used for scientific discovery and commercial manufacturing, fundamental physical phenomena shift, leading to changes in immune function, metabolic processes, and other physiological responses,” the authors explained.

One such study—the NASA Twins Study—was a landmark, year-long experiment (2015-2016) where astronaut Scott Kelly spent 340 days aboard the ISS while his identical twin, Mark Kelly, remained on Earth. The study tracked changes across genetics, physiology, cognition, and the microbiome and found altered gene expression, shifts in telomere length, and changes in the gut microbiome.

However, many of these changes reversed or returned to normal after astronaut Kelly returned to Earth. The study did identify some persistent changes, such as increased numbers of short telomeres and disruptions in gene expression, which could be relevant for longer space missions.

The newly reported UC San Diego-led study builds on the findings of the Twins Study and the seminal work of the Space Omics and Medical Atlas group, which published 44 scientific papers on aerospace medicine and space biology in Nature.

By focusing specifically on HSPCs, the study in Cell Stem Cell offers a detailed mechanistic look at how space triggers molecular aging, something the Twins Study hinted at but could not fully explore at the cellular level. “Few studies have investigated the combined stressors associated with the extreme environment of space on functional processes regulated at the HSPC level that will be vital for understanding the human-specific limitations of long-duration spaceflight,” Jameison and team noted.
To conduct their study, the researchers, including a team at Space Tango, developed a novel “nanobioreactor” platform—miniaturized 3D biosensing systems that allowed human stem cells to be cultured in space and monitored with AI-powered imaging tools. “To determine whether HSPC fitness is impaired and immune dysfunction derives from the loss of normal HSPC homeostasis in space compared with terrestrial environments, we developed a 3D biosensing nanobioreactor system that enables prolonged maintenance of human HSPCs,” they explained.

Their results showed that human HSPCs exposed to 32 to 45 days of spaceflight showed hallmark features of aging. Spaceflight was found to trigger a range of changes in blood-forming stem cells that closely resemble what happens to these cells as we age. The cells became more active than normal, burning through their reserves and losing the ability to rest and recover—a key trait that allows stem cells to regenerate over time.

The results showed that the ability of HSPCs in space to make healthy new cells declined, while signs of molecular wear-and-tear, such as DNA damage and shorter chromosome ends—telomeres—became more pronounced.

The cells also showed signs of inflammation and stress inside their mitochondria and began activating hidden sections of the genome that are normally kept quiet to maintain stability. These stress responses can impair immune function and increase the risk of diseases.

“…we observed inflammatory cytokine changes, mitochondrial DNA amplification, protein translation, and mitochondrial gene expression changes, which corroborated previous studies showing inflammatory cytokine and mitochondrial deregulation in longer-duration spaceflight,” the scientists reported.

“Together, these findings suggest a diminished capacity of HSPCs to maintain their function upon return from spaceflight, which is consistent with accelerated stem cell aging.”

Notably, when these space-exposed cells were later placed in a young, healthy environment, some of the damage began to reverse, suggesting it may be possible to rejuvenate aging cells with the right interventions. “Space-associated HSPC aging can be partially reversed on young stroma,” the scientists further stated.

“We’re excited this breakthrough work is being published to the wider scientific and space communities,” said Twyman Clements, president and co-founder of Space Tango. “Like many accomplishments, this one was a team effort bringing together the Integrated Space Stem Cell Orbital Research Center within SSCI, Space Tango, and others. Coupling Space Tango’s CubeLab capabilities, specifically the persistent microscopy, has enabled this work and will continue to do so in the future.”

The research team plans to extend their work with additional ISS missions and astronaut-based studies, focusing on real-time monitoring of molecular changes and potential pharmaceutical or genetic countermeasures to protect human health in space and beyond. To date, the SSCI has conducted 17 missions to the ISS.

The authors stated, “Together, our results reveal spaceflight-associated HSPC aging, thereby setting the stage for the development of countermeasures to enable long-duration human spaceflight and establish AI-driven technologies for predicting HSPC functional decline under conditions of macroenvironmental stress in space and terrestrially…Ultimately, these studies may provide guidance for therapeutic strategies to mitigate space-specific changes in the expanding space economy, as well as space-accelerated models of aging and age-related diseases, such as cancer.”

“Space experiments are so complex that they force you to do better science on the ground,” continued Jamieson. “Space research has accelerated technological advancements on Earth, making ground-based research easier and more relevant to human health. What we have learned about cancer from our studies in space is absolutely remarkable.”

In their paper the researchers suggested, “Moreover, the methods and findings from our study can help facilitate future studies to predict and understand the observed molecular changes for longer-duration or further destination spaceflight missions.”

Gilead Sciences broke ground on its new Pharmaceutical Development and Manufacturing (PDM) Technical Development Center (NTDC) at the company’s Foster City headquarters in California. This milestone marks continued momentum in Gilead’s multi-year strategy to drive growth and scientific leadership across virology, oncology, and inflammation, increasingly built on growing biologics capabilities, according to Daniel O’Day, chairman and CEO.

“This new facility is part of our vision for delivering next generation therapies and a cornerstone of Gilead’s $32 billion investment commitment in the United States,” said O’Day. “We have multiple construction projects underway, all of which will generate thousands of American jobs and help to drive U.S. leadership in global biopharma innovation.”

The five-story, 180,000-sq-foot facility will serve as a hub for innovation and collaboration across technical development and manufacturing teams. Designed with flexible pilot lab space and advanced digital infrastructure, the NTDC will accelerate technology transfer and support the advancement of next-generation biologics across Gilead’s pipeline, predicts O’Day, adding that the facility will strengthen Gilead’s biologics capacity and capabilities. It will feature digitally enabled systems, autonomous robotics, and real-time digital monitoring.

This groundbreaking is part of a broader expansion at Gilead’s Foster City headquarters. In addition to the NTDC, the company is currently developing two others: a new research building designed to accelerate scientific discovery, already under construction, and a biologics manufacturing facility that will expand domestic production capacity. These current investments further build on Gilead’s strong history of U.S. investment, with more than $15 billion over the last decade, pointed out O’Day.