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Tag: FDA approval

  • FDA OKs libido-boosting pill for older women who have gone through menopause

    U.S. health officials have expanded approval of a much-debated drug aimed at boosting female libido, saying the once-a-day pill can now be taken by postmenopausal women up to 65 years old.The announcement Monday from the Food and Drug Administration broadens the drug’s use to older women who have gone through menopause. The pill, Addyi, was first approved 10 years ago for premenopausal women who report emotional stress due to low sex drive.Addyi, marketed by Sprout Pharmaceuticals, was initially expected to become a blockbuster drug, filling an important niche in women’s health. But the drug came with unpleasant side effects including dizziness and nausea, and it carries a safety warning about the dangers of combining it with alcohol.The boxed warning cautions that drinking while consuming the pill can cause dangerously low blood pressure and fainting. If patients have several drinks, the label recommends waiting a few hours before taking the drug, or skipping one dose.Sales of Addyi, which acts on brain chemicals that affect mood and appetite, fell short of Wall Street’s initial expectations. In 2019, the FDA approved a second drug for low female libido, an on-demand injection that acts on a different set of neurological chemicals.Sprout CEO Cindy Eckert said in a statement the approval “reflects a decade of persistent work with the FDA to fundamentally change how women’s sexual health is understood and prioritized.” The company, based in Raleigh, North Carolina, announced the FDA update in a press release Monday.The medical condition for a troublingly low sexual appetite, called hypoactive sexual desire disorder, has been recognized since the 1990s and is thought to affect a significant portion of American women, according to surveys. After the blockbuster success of Viagra for men in the 1990s, drugmakers began pouring money into research and potential therapies for sexual dysfunction in women.But diagnosing the condition is complicated because of how many factors can affect libido, especially after menopause, when falling hormone levels trigger a number of biological changes and medical symptoms. Doctors are supposed to rule out a number of other issues, including relationship problems, medical conditions, depression and other mental disorders, before prescribing medication.The diagnosis is not universally accepted, and some psychologists argue that low sex drive should not be considered a medical problem.The FDA rejected Addyi twice prior to its 2015 approval, citing the drug’s modest effectiveness and worrisome side effects. The approval came after a lobbying campaign by the company and its supporters, Even the Score, which framed the lack of options for female libido as a women’s rights issue.

    U.S. health officials have expanded approval of a much-debated drug aimed at boosting female libido, saying the once-a-day pill can now be taken by postmenopausal women up to 65 years old.

    The announcement Monday from the Food and Drug Administration broadens the drug’s use to older women who have gone through menopause. The pill, Addyi, was first approved 10 years ago for premenopausal women who report emotional stress due to low sex drive.

    Addyi, marketed by Sprout Pharmaceuticals, was initially expected to become a blockbuster drug, filling an important niche in women’s health. But the drug came with unpleasant side effects including dizziness and nausea, and it carries a safety warning about the dangers of combining it with alcohol.

    The boxed warning cautions that drinking while consuming the pill can cause dangerously low blood pressure and fainting. If patients have several drinks, the label recommends waiting a few hours before taking the drug, or skipping one dose.

    Sales of Addyi, which acts on brain chemicals that affect mood and appetite, fell short of Wall Street’s initial expectations. In 2019, the FDA approved a second drug for low female libido, an on-demand injection that acts on a different set of neurological chemicals.

    Sprout CEO Cindy Eckert said in a statement the approval “reflects a decade of persistent work with the FDA to fundamentally change how women’s sexual health is understood and prioritized.” The company, based in Raleigh, North Carolina, announced the FDA update in a press release Monday.

    The medical condition for a troublingly low sexual appetite, called hypoactive sexual desire disorder, has been recognized since the 1990s and is thought to affect a significant portion of American women, according to surveys. After the blockbuster success of Viagra for men in the 1990s, drugmakers began pouring money into research and potential therapies for sexual dysfunction in women.

    But diagnosing the condition is complicated because of how many factors can affect libido, especially after menopause, when falling hormone levels trigger a number of biological changes and medical symptoms. Doctors are supposed to rule out a number of other issues, including relationship problems, medical conditions, depression and other mental disorders, before prescribing medication.

    The diagnosis is not universally accepted, and some psychologists argue that low sex drive should not be considered a medical problem.

    The FDA rejected Addyi twice prior to its 2015 approval, citing the drug’s modest effectiveness and worrisome side effects. The approval came after a lobbying campaign by the company and its supporters, Even the Score, which framed the lack of options for female libido as a women’s rights issue.

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  • Trump’s touting of an unproven autism drug surprised many, including the doctor who proposed it

    When President Donald Trump’s administration announced it would repurpose an old, generic drug as a new treatment for autism, it came as a surprise to many experts — including the physician who suggested the idea to the nation’s top health officials.Dr. Richard Frye told The Associated Press that he’d been talking with federal regulators about developing his own customized version of the drug for children with autism, assuming more research would be required.”So we were kinda surprised that they were just approving it right out of the gate without more studies or anything,” said Frye, an Arizona-based child neurologist who has a book and online education business focused on the experimental treatment.It’s another example of the quick rollout of the Trump administration’s Monday announcement on autism, which critics say has elevated an unproven drug that needs far more study before being approved as a credible treatment for the complex brain disorder.A spokesperson for the Republican administration did not immediately respond to a request for comment Wednesday morning.The nation’s leading autism groups and researchers quickly distanced themselves from the decision on leucovorin, a derivative of vitamin B, calling the studies supporting its use “very weak” and “very small.””We have nothing resembling even moderate evidence that leucovorin is an effective treatment for autism symptoms,” said David Mandell, a psychiatrist at the University of Pennsylvania.Mandell and other researchers say the evidence suggests autism is mostly rooted in genetics, with input from other factors, including the age of the child’s father.Nevertheless, a growing number of doctors are prescribing the medication, repurposing versions used for chemotherapy or ordering new formulations from compounding pharmacies.Many researchers agree the drug warrants additional study, particularly for patients with a deficiency of folate, or vitamin B9, in the brain that may play a role in autism. But for now, they say, it should only be taken in carefully controlled clinical trials.”We often say our job is to stay between the yellow lines,” said Dr. Lawrence Gray, a pediatric developmental specialist at Northwestern University. “When people just decide to go outside of current guidelines, then they’re outside of that. And nobody knows what’s going to happen out there.”Related video below: Parents, doctors react to Trump administration claims about Tylenol and autismThe evidence for leucovorin isn’t settledThe case for leucovorin’s use in autism begins with established science but quickly veers into uncertain terrain.When metabolized, the drug turns into folate, which is essential for healthy prenatal development and is recommended before and during pregnancy. But far less is known about its role after birth.The issue caught the attention of Frye and others more than 20 years ago, when research suggested some people with autism had low levels of folate in the brain due to antibodies blocking the vitamin’s absorption.The theory linking autism to folate levels was mostly abandoned, however, after research showed that the siblings of people with autism can also have low folates without any symptoms of the condition.”I honestly thought this had died out as a theory for autism and was shocked to see its reemergence,” Mandell said.In 2018, Frye and his colleagues published a study of 48 children in which those taking leucovorin performed better on several language measures than those taking a placebo.Four small studies in other countries, including China and Iran, showed similar results, albeit using different doses, metrics and statistical analyses, which researchers say is problematic.Frye struggled to get funding to continue within the traditional academic system.”I decided to move out of academia to be more innovative and actually do some of this stuff,” he said.Researchers saw an opening to approach Trump’s top health officialsEarlier this year, Frye and several other researchers formed a new entity, the Autism Discovery Coalition, to pitch their work to Trump administration officials including Health Secretary Robert F. Kennedy Jr.”After Kennedy got in, we thought they’d hopefully be friendly to autism scientists,” he said.An August meeting with National Institutes of Health Director Jay Bhattacharya quickly led to further discussions with the Food and Drug Administration about testing a proprietary, purified version of leucovorin.A new formulation of the decades-old drug would mean new patents, allowing Frye and his yet-to-be-formed drug company to charge far more than the cheap generics currently on the market.”We have a lot of investors who are excited about leucovorin and want to do something high quality for kids with autism,” he said.But the FDA’s announcement Monday may have scuttled that plan. Instead of previewing a new version, the agency said it would simply update the label on the generic drug to mention use in boosting folate brain levels, including for patients with autism. That’s expected to encourage more doctors to prescribe it and insurers to cover it.Promising autism treatments often fail after more studySpecialists who have spent decades treating autistic patients say it’s important to proceed carefully.Gray recalls other experimental treatments that initially looked promising only to fail in larger studies.”Small studies often find populations that are very motivated,” Gray said. “But when those therapies are moved into larger studies, the initial positive findings often disappear.”Among the challenges facing leucovorin: There isn’t agreement about what portion of autism patients have the folate-blocking antibodies supposedly targeted by the drug.Frye screens his patients for the antibodies using a test developed at a laboratory at the State University of New York. Like many specialty tests, it has not been reviewed by the FDA.Gray says the only way to definitively test for the antibodies would be by extracting cranial fluid from children with autism through a spinal tap.”That’s a big limiting factor in having these large, randomized controlled trials,” Gray said.Related video below: Get the Facts on the White House’s claims linking Tylenol and autismOnline sources are driving interest from parentsWhile the Trump administration discusses fast-tracking leucovorin, interest in the drug continues to swirl online, including in forums and social media groups for parents of children with autism.Brian Noonan, of Phoenix, found out about the drug earlier this year after asking ChatGPT for the best autism drug options for his 4-year-old son.The FDA has never approved any drug for the underlying causes of autism, but the chatbot directed Noonan to Frye’s research.After an evaluation and confirmatory blood test, the boy started on a formulation of the drug from a compounding pharmacy in June.Within days, Noonan says, he saw improvement in his son’s ability to make eye contact and form sentences.”He’s not cured, but these are just areas of improvement,” Noonan said. “It’s been a big thing for us.”

    WASHINGTON —

    When President Donald Trump’s administration announced it would repurpose an old, generic drug as a new treatment for autism, it came as a surprise to many experts — including the physician who suggested the idea to the nation’s top health officials.

    Dr. Richard Frye told The Associated Press that he’d been talking with federal regulators about developing his own customized version of the drug for children with autism, assuming more research would be required.

    “So we were kinda surprised that they were just approving it right out of the gate without more studies or anything,” said Frye, an Arizona-based child neurologist who has a book and online education business focused on the experimental treatment.

    It’s another example of the quick rollout of the Trump administration’s Monday announcement on autism, which critics say has elevated an unproven drug that needs far more study before being approved as a credible treatment for the complex brain disorder.

    A spokesperson for the Republican administration did not immediately respond to a request for comment Wednesday morning.

    The nation’s leading autism groups and researchers quickly distanced themselves from the decision on leucovorin, a derivative of vitamin B, calling the studies supporting its use “very weak” and “very small.”

    “We have nothing resembling even moderate evidence that leucovorin is an effective treatment for autism symptoms,” said David Mandell, a psychiatrist at the University of Pennsylvania.

    Mandell and other researchers say the evidence suggests autism is mostly rooted in genetics, with input from other factors, including the age of the child’s father.

    Nevertheless, a growing number of doctors are prescribing the medication, repurposing versions used for chemotherapy or ordering new formulations from compounding pharmacies.

    Many researchers agree the drug warrants additional study, particularly for patients with a deficiency of folate, or vitamin B9, in the brain that may play a role in autism. But for now, they say, it should only be taken in carefully controlled clinical trials.

    “We often say our job is to stay between the yellow lines,” said Dr. Lawrence Gray, a pediatric developmental specialist at Northwestern University. “When people just decide to go outside of current guidelines, then they’re outside of that. And nobody knows what’s going to happen out there.”

    Related video below: Parents, doctors react to Trump administration claims about Tylenol and autism

    The evidence for leucovorin isn’t settled

    The case for leucovorin’s use in autism begins with established science but quickly veers into uncertain terrain.

    When metabolized, the drug turns into folate, which is essential for healthy prenatal development and is recommended before and during pregnancy. But far less is known about its role after birth.

    The issue caught the attention of Frye and others more than 20 years ago, when research suggested some people with autism had low levels of folate in the brain due to antibodies blocking the vitamin’s absorption.

    The theory linking autism to folate levels was mostly abandoned, however, after research showed that the siblings of people with autism can also have low folates without any symptoms of the condition.

    “I honestly thought this had died out as a theory for autism and was shocked to see its reemergence,” Mandell said.

    In 2018, Frye and his colleagues published a study of 48 children in which those taking leucovorin performed better on several language measures than those taking a placebo.

    Four small studies in other countries, including China and Iran, showed similar results, albeit using different doses, metrics and statistical analyses, which researchers say is problematic.

    Frye struggled to get funding to continue within the traditional academic system.

    “I decided to move out of academia to be more innovative and actually do some of this stuff,” he said.

    Researchers saw an opening to approach Trump’s top health officials

    Earlier this year, Frye and several other researchers formed a new entity, the Autism Discovery Coalition, to pitch their work to Trump administration officials including Health Secretary Robert F. Kennedy Jr.

    “After Kennedy got in, we thought they’d hopefully be friendly to autism scientists,” he said.

    An August meeting with National Institutes of Health Director Jay Bhattacharya quickly led to further discussions with the Food and Drug Administration about testing a proprietary, purified version of leucovorin.

    A new formulation of the decades-old drug would mean new patents, allowing Frye and his yet-to-be-formed drug company to charge far more than the cheap generics currently on the market.

    “We have a lot of investors who are excited about leucovorin and want to do something high quality for kids with autism,” he said.

    But the FDA’s announcement Monday may have scuttled that plan. Instead of previewing a new version, the agency said it would simply update the label on the generic drug to mention use in boosting folate brain levels, including for patients with autism. That’s expected to encourage more doctors to prescribe it and insurers to cover it.

    Promising autism treatments often fail after more study

    Specialists who have spent decades treating autistic patients say it’s important to proceed carefully.

    Gray recalls other experimental treatments that initially looked promising only to fail in larger studies.

    “Small studies often find populations that are very motivated,” Gray said. “But when those therapies are moved into larger studies, the initial positive findings often disappear.”

    Among the challenges facing leucovorin: There isn’t agreement about what portion of autism patients have the folate-blocking antibodies supposedly targeted by the drug.

    Frye screens his patients for the antibodies using a test developed at a laboratory at the State University of New York. Like many specialty tests, it has not been reviewed by the FDA.

    Gray says the only way to definitively test for the antibodies would be by extracting cranial fluid from children with autism through a spinal tap.

    “That’s a big limiting factor in having these large, randomized controlled trials,” Gray said.

    Related video below: Get the Facts on the White House’s claims linking Tylenol and autism

    Online sources are driving interest from parents

    While the Trump administration discusses fast-tracking leucovorin, interest in the drug continues to swirl online, including in forums and social media groups for parents of children with autism.

    Brian Noonan, of Phoenix, found out about the drug earlier this year after asking ChatGPT for the best autism drug options for his 4-year-old son.

    The FDA has never approved any drug for the underlying causes of autism, but the chatbot directed Noonan to Frye’s research.

    After an evaluation and confirmatory blood test, the boy started on a formulation of the drug from a compounding pharmacy in June.

    Within days, Noonan says, he saw improvement in his son’s ability to make eye contact and form sentences.

    “He’s not cured, but these are just areas of improvement,” Noonan said. “It’s been a big thing for us.”

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  • FDA clears first digital treatment for depression, but experts caution that research is still early

    FDA clears first digital treatment for depression, but experts caution that research is still early

    The US Food and Drug Administration is allowing the use of Rejoyn, the first prescription digital treatment for major depressive disorder.

    Rejoyn, made by Otsuka Pharmaceutical and Click Therapeutics, is a smartphone app intended for use alongside antidepressant medications for people 22 and older who have a diagnosis of major depressive disorder. It employs a six-week program that combines a new approach called cognitive-emotional training and cognitive behavioral therapy lessons, according to a news release.

    Since Rejoyn is classified as a low- to medium-risk medical device, it needed only to prove that it is “substantially equivalent” to another marketed device – meaning it is just as safe and effective – to gain FDA clearance.

    “Rejoyn represents a novel and exciting adjunctive treatment option to address major depressive disorder symptoms that complements the current standard of care,” Dr. John Kraus, executive vice president and chief medical officer at Otsuka, said in the release. “While traditional approaches are often effective, many are left with only a partial response to treatment.”

    Depression is one of the most common mental health disorders in the US. About 18% of American adults – more than 1 in 6 – say they are depressed or receiving treatment for depression, a 2023 Gallup report found. Research has also found that up to 30% of people who take antidepressant medications are partial responders, meaning they continue to have depressive symptoms while using the drugs.

    Rejoyn is designed to serve as an adjunct to antidepressants for these partial responders, according to the news release. The app uses a form of cognitive-emotional training called Emotional Faces Memory Task, in which people are asked to identify and compare emotions displayed on a series of faces. Preliminary research shows that these exercises may stimulate the amygdala and the dorsolateral prefrontal cortex – regions of the brain that are thought to be involved in depression – and have antidepressant effects.

    “Rejoyn has a neuromodulatory mechanism designed to act like physical therapy for the brain by delivering personalized, consistent brain-training exercises designed to help improve connections in the brain regions affected by depression,” Dr. Brian Iacoviello, scientific adviser at Click Therapeutics and a co-inventor of Emotional Faces Memory Task, said in the news release.

    Dr. John Torous, director of the Division of Digital Psychiatry at Beth Israel Deaconess Medical Center, who was not involved in the development of Rejoyn, said that this cognitive-emotional training approach is not a well-established mechanism and that the research is still exploratory.

    The FDA clearance for Rejoyn was granted based on results from a clinical trial involving 386 people ages 22 to 64 who had a diagnosis of major depressive disorder that was not responsive to antidepressants. They were assigned to use either the Rejoyn app or a sham app that gave memory tasks that did not involve cognitive-emotional training or cognitive behavioral therapy.

    The study found that while participants using the Rejoyn app showed an improvement in depressive symptoms from baseline, the average change was not significantly different from the change observed with the sham app. There were no side effects reported in the trial.

    Torous said that while it is important to note that the trial did not prove that Rejoyn has a statistically significant benefit, the app is also not designed to be a standalone treatment.

    “If the benefit is minimal but the risks are minimal, perhaps there’s no harm in trying it,” he said. “Hopefully, we see more evidence come out in the future, because as a clinician psychiatrist, I want to make sure people use something that is going to make them better.”

    Otsuka Pharmaceutical said it is evaluating additional areas of research, including other indications and patient populations, but did not outline any specific follow-up studies.

    Rejoyn will require a prescription for download and will become available in late 2024, according to the news release. Otsuka said it will make try to make the tool “accessible and affordable” but did not specify the price.

    Torous noted that insurance companies may not cover the app because it did not show significant effect in clinical trials. FDA clearance, he said, does not guarantee insurance approval.

    “The next frontier is going to be educating everyone on the risks and benefits of these tools. Many clinicians may not be ready or prepared to begin prescribing” them, he said.

    There is also the question of how engaged patients will be with the app, Torous said. The Rejoyn study found that 88% of participants completed at least 12 of the 18 treatment sessions.

    Thousands of mental health apps geared toward various mental health disorders don’t require a prescription, Torous said. Doctors need to understand the specific needs and preferences of their patients before recommending a digital tool, he said.

    “I think that patients and clinicians are curious and excited to learn more, but both want to understand the risks and benefits,” Torous said. “There is an opportunity cost if you do something that is not effective.”

    The-CNN-Wire & 2023 Cable News Network, Inc., a Warner Bros. Discovery Company. All rights reserved.

    CNNWire

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  • The Ozempic Revolution Is Stuck

    The Ozempic Revolution Is Stuck

    Millions more Americans are now eligible for obesity drugs. But the injections remain maddeningly hard to find.

    Illustration by The Atlantic. Source: Getty.

    The irony undergirding the new wave of obesity drugs is that they initially weren’t created for obesity at all. The weight loss spurred by Ozempic, a diabetes drug in the class of so-called GLP-1 agonists, gave way to Wegovy—the same drug, repackaged for obesity. Zepbound, another medication, soon followed. Now these drugs have a new purpose: heart health.

    On Friday, the FDA approved the use of Wegovy for reducing the risk of heart attack, stroke, and death in adults who are overweight and have cardiovascular disease. The move had been anticipated since the publication of a landmark trial in the fall, which showed the drug’s profound effects on cardiovascular  health. The decision could usher in a new era where GLP-1 drugs become mainstream, opening up access to millions of Americans who previously didn’t qualify for Wegovy.

    Some of the obstacles stopping people from getting the drug may also begin to crumble. Insurance companies commonly deny coverage of Wegovy because obesity is seen as a cosmetic concern rather than a medical one, but that argument may not hold up for cardiovascular disease. “This new FDA indication is HUGE,” Katherine Saunders, an obesity-medicine physician at Weill Cornell Medicine, told me in an email. Wegovy may soon be within reach for many more Americans—that is, if they can find it.

    In practice, Wegovy is maddeningly hard to get hold of. Shortages of injectable semaglutide, the active ingredient in Wegovy and Ozempic, have been ongoing since March 2022; currently, most doses of Wegovy are in limited supply. As the popularity of semaglutide has skyrocketed, demand has completely outstripped the capacity of its manufacturer, Novo Nordisk. The drug comes in injection pens containing a glass vial; “these are not easy products to make,” Lars Fruergaard Jørgensen, the CEO of Novo Nordisk, said in August. In response to the shortages, the company withheld its supply of lower Wegovy doses last year. Because treatment on the medication must begin in low doses, this meant that new patients who wanted to start on Wegovy functionally couldn’t. In January, the company began “more than doubling the amount of the lower-dose strengths” of the drug, a Novo Nordisk spokesperson told me, and it plans to gradually increase overall supply throughout the rest of the year.

    The ongoing shortages have left providers and patients feeling stuck. “It is devastating to prescribe a lifesaving medication for a patient and then find out it’s not covered or we can’t locate supply,” Saunders said. Doctors are scrambling to make do with what’s available. Ivania Rizo, an endocrinologist at Boston Medical Center, told me she has had to turn to older GLP-1 drugs such as Saxenda to “bridge” patients to higher doses of Wegovy, although now that is in shortage too. Patients can spend each day calling pharmacy after pharmacy in search of one with Wegovy in stock, Rizo said. In desperation, some have turned to versions of the drug that are custom-made by compounding pharmacies with little oversight, despite the FDA expressing concerns about them. The shots are supposed to be taken weekly, but others have attempted to stretch their doses beyond that.

    That the new FDA approval could very mainstream obesity drugs may create long-needed pressure to help resolve these shortages. It makes clear that Wegovy is a lifesaving medication not only for people with obesity but also for those with cardiovascular disease—the leading cause of death in the U.S.—putting the impetus on Novo Nordisk to ramp up production. But in the short term, the access issues may persist. “The new approval is very likely to worsen shortages, because the demand for Wegovy will continue to climb—now at an even faster pace,” Saunders said.

    If patients think they’re stuck now, they’re about to feel entrenched. Wegovy is the only obesity drug that has been approved to reduce the risk of heart attacks, but none of its competitors is easily available either. Supplies of certain dosages of Eli Lilly’s Mounjaro, a diabetes drug whose active ingredient is sold for obesity as Zepbound, are limited, and shortages are expected later this year. “We need supply to increase dramatically,” Saunders said. Both Novo Nordisk and Eli Lilly have invested heavily in expanding production capacity, but some of the new plants won’t open until 2029.

    For all of its advantages, the FDA approval has a sobering effect on the unrelenting hype around GLP-1s. So much of the excitement around obesity drugs has focused on the future, as dozens of pharmaceutical companies develop more powerful drugs, and commentators imagine a world without obesity. In the process, the issues of the present have gone overlooked. More drugs won’t make much of a difference if the drugs themselves are out of reach.

    Yasmin Tayag

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  • Are You Sure You Want an Ozempic Pill?

    Are You Sure You Want an Ozempic Pill?

    Within the first five seconds of a recent Ozempic commercial, a sky-blue injector pen tumbles toward the viewer, encircled by a big red O. Obesity drugs have become so closely associated with injections that the two are virtually synonymous. Like Ozempic, whose name is now a catchall term for obesity drugs, Wegovy and Zepbound come packaged in Sharpie-like injection pens that patients self-administer once a week. Patients “don’t come in asking for Wegovy,” Laura Davisson, a professor of medical weight management at West Virginia University, told me. “They come in asking for one of ‘those injectables.’”

    Needles are the present, but supposedly not the future. Nobody really likes injections, and taking a pill would be far easier. In the frenzy over obesity drugs, a class known as GLP-1 agonists, drugmakers have raced to create them in pill form, and Wall Street investors are hungry at the prospect. Earlier this year, Pfizer’s CEO, Albert Bourla, estimated that obesity pills could be worth $30 billion, or a third of the total obesity-drug market. Because people have a “preference” for pills, he said at a conference, they will be what ultimately “unlocks the market” for obesity medications. By one count, at least 32 oral GLP-1 drugs, from many different companies, are in the works.

    But a future dominated by obesity pills is hardly certain. So far, the only oral GLP-1 that exists is a pill for diabetes called Rybelsus. Like Ozempic and Wegovy, its active ingredient is a compound called semaglutide, but the shots come in far more powerful doses, making it possible to lose even more weight. Developing oral obesity drugs that are as tolerable and effective as their injectable counterparts has so far been a challenge. Earlier this month, Pfizer stopped testing one of its pill candidates, citing concerns about side effects and patient adherence. Even when pills do come to market, doctors told me, there’s no guarantee that people will flock to them.

    That drugmakers view the injectable nature of GLP-1s as one of their biggest flaws is no surprise. Getting a shot is a broadly despised experience, something people generally tolerate rather than choose. Children get stickers for enduring immunizations; adults who get vaccinated do so only because they must (and they are often rewarded with stickers too). The CDC estimates that one in four adults, and two out of three children, have strong fears about needles. “Some people hate needles, plain and simple,” Ted Kyle, an obesity-policy expert, told me.

    But not all needles are made equal. Wegovy and Zepbound are injected subcutaneously, or just under the skin. Relative to COVID or flu shots, which are jabbed into muscle, they don’t cause much discomfort. “I’ve been really surprised at how receptive my patients have been to using injectable medications,” Davisson said. Other doctors I spoke with agreed. “More patients than you would expect really don’t mind injectables,” because they’re easy and relatively painless to administer, Katherine Saunders, a clinical-medicine professor at Weill Cornell Medicine, told me.

    The unobtrusive dosing schedule of the injectables adds to their appeal. Wegovy and Zepbound are administered once weekly, unlike many of the pills in development, which are meant to be taken once or more daily. That can be a hassle, especially if they have to be taken at the same time every day, or if they come with restrictions on eating or drinking. “For some people, it’s easier to take an injection and forget about it for a week” than to remember to take a pill every day, Eduardo Grunvald, an obesity-medicine physician at UC San Diego Health, told me. Assuming pills are preferable to shots is a “knee-jerk reaction,” he added.

    Despite the unexpected upsides of the shots, they’re far from perfect. Making injectable pens is generally more expensive than pills and requires a lot of hardware, including the pen casing, cap, and needle cover. On top of that, the injectable obesity drugs must be refrigerated before they are first used, adding to storage and production costs. Pills are generally shelf-stable and don’t require much packaging beyond a child-proof bottle. Saunders predicts they would be less expensive and less prone to shortages that have plagued Wegovy.

    Still, creating an obesity pill isn’t as simple as packaging the same drugs in capsule form. Drugmakers have already run into a number of issues. Absorption is a big one: Because pills pass through the stomach before entering the bloodstream, they must be able to withstand a large degree of degradation. One way to get these drugs to lead to greater weight loss is to increase the dose. While the highest dose of Wegovy is 2.4 milligrams, Rybelsus maxes out at 14 milligrams.

    Hiking up the dose seems to work, though doing so could have consequences beyond weight loss. All GLP-1 drugs come with a range of unpleasant side effects involving the gastrointestinal system, and patients report nausea at similar rates in Rybelsus and Ozempic, according to the FDA. But this may differ in practice, as other doctors have noted. Saunders said that her patients on oral semaglutide report more nausea than those using injectables. Regardless, newer oral medications may have even more distinct differences, as drugmakers race to create more potent pills. In Pfizer’s discontinued trial of danuglipron, nausea rates reached up to 73 percent.

    Drugmakers also skirt the issue of degradation by pursuing sturdier drugs. The problem with semaglutide is that it’s a peptide—essentially a small protein—precisely the kind of molecule that the stomach excels at digesting. Some new drugs in the pipeline are so-called non-peptide small molecules, which are sturdier but still have the same biological effect. Orforglipron, a pill that Eli Lilly is testing, falls into this category, as does danuglipron, the drug responsible for Pfizer’s recent setbacks. Small-molecule drugs have the added benefit of being cheaper to produce at scale than peptides, Kyle, the obesity-policy expert, added.

    Another pesky problem with oral drugs is that they tend to come with strict dosing requirements. People on Rybelsus, for example, are instructed to take it 30 minutes before eating or drinking anything and can drink only four ounces of plain water along with it, because otherwise absorption could be compromised. “It can be a nuisance,” Grunvald said. Similarly bothersome instructions likely played a part in the drop-out rates reaching more than 50 percent in Pfizer’s recently discontinued trial: Danuglipron had to be taken twice daily. “A lot of people found it not worth the trouble,” Kyle said, noting that Pfizer is still pursuing a once-daily version of the same drug. A recent review of GLP-1 drugs showed that, compared with the injectable form, oral semaglutide is associated with lower rates of side-effect reporting but higher discontinuation rates, potentially reflecting its bothersome dosage requirements.

    Despite these hurdles, it seems inevitable that obesity-drug pills will eventually become available. Novo Nordisk is expected to file for FDA approval for its high-dose semaglutide obesity pill this year; Pfizer is forging ahead with a once-daily version of danuglipron, with more data expected “in the first half of 2024,” a spokesperson told me. A report from BMO Equity Research published in September predicted that oral formulations could be approved “by the late 2020s.” The biggest upside to pills may not be that they are pills but that they will, eventually, be cheaper than injectables—and cost is among the biggest impediments to more people taking obesity drugs.

    Whether they’ll replace injectables outright is far from certain. “It will come down to patient preference,” Grunvald said. Most likely, pills and injections will coexist to meet different needs, and perhaps even be used together to treat individual patients. In the so-called phased approach, obesity treatment could start with more expensive and powerful injectable drugs, then transition to less potent but cheaper orals for the long term. Eli Lilly, for one, sees its oral candidate, orforglipron, as a potential weight-loss-maintenance drug.

    There is so much competition in the obesity-drug space that future medications may take more unexpected forms. Amgen is studying a once-monthly injection; Novo Nordisk is developing a hydrogel form of semaglutide that would need to be taken only three times a year. If the future of obesity drugs will come down to what patients prefer, then the more options, the better.

    Yasmin Tayag

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  • The CRISPR Era Is Here

    The CRISPR Era Is Here

    When Victoria Gray was still a baby, she started howling so inconsolably during a bath that she was rushed to the emergency room. The diagnosis was sickle-cell disease, a genetic condition that causes bouts of excruciating pain—“worse than a broken leg, worse than childbirth,” one doctor told me. Like lightning crackling in her body is how Gray, now 38, has described the pain. For most of her life, she lived in fear that it could strike at any moment, forcing her to drop everything to rush, once again, to the hospital.

    After a particularly long and debilitating hospitalization in college, Gray was so weak that she had to relearn how to stand, how to use a spoon. She dropped out of school. She gave up on her dream of becoming a nurse.

    Four years ago, she joined a groundbreaking clinical trial that would change her life. She became the first sickle-cell patient to be treated with the gene-editing technology CRISPR—and one of the first humans to be treated with CRISPR, period. CRISPR at that point had been hugely hyped, but had largely been used only to tinker with cells in a lab. When Gray got her experimental infusion, scientists did not know whether it would cure her disease or go terribly awry inside her. The therapy worked—better than anyone dared to hope. With her gene-edited cells, Gray now lives virtually symptom-free. Twenty-nine of 30 eligible patients in the trial went from multiple pain crises every year to zero in 12 months following treatment.

    The results are so astounding that this therapy, from Vertex Pharmaceuticals and CRISPR Therapeutics, became the first CRISPR medicine ever approved, with U.K. regulators giving the green light earlier this month; the FDA appears prepared to follow suit in the next two weeks. No one yet knows the long-term effects of the therapy, but today Gray is healthy enough to work full-time and take care of her four children. “Now I’ll be there to help my daughters pick out their wedding dresses. And we’ll be able to take family vacations,” she told NPR a year after her treatment. “And they’ll have their mom every step of the way.”

    The approval is a landmark for CRISPR gene editing, which was just an idea in an academic paper a little more than a decade ago—albeit one already expected to cure incurable diseases and change the world. But how, specifically? Not long after publishing her seminal research, Jennifer Doudna, who won the Nobel Prize in Chemistry with Emmanuelle Charpentier for their pioneering CRISPR work, met with a doctor on a trip to Boston. CRISPR could cure sickle-cell disease, he told her. On his computer, he scrolled through DNA sequences of cells from a sickle-cell patient that his lab had already edited with CRISPR. “That, for me, personally, was one of those watershed moments,” Doudna told me. “Okay, this is going to happen.” And now, it has happened. Gray and patients like her are living proof of gene-editing power. Sickle-cell disease is the first disease—and unlikely the last—to be transformed by CRISPR.

    All of sickle-cell disease’s debilitating and ultimately deadly effects originate from a single genetic typo. A small misspelling in Gray’s DNA—an A that erroneously became a T—caused the oxygen-binding hemoglobin protein in her blood to clump together. This in turn made her red blood cells rigid, sticky, and characteristically sickle shaped, prone to obstructing blood vessels. Where oxygen cannot reach, tissue begins to die. Imagine “if you put a tourniquet on and walked away, or if you were having a heart attack all the time,” says Lewis Hsu, a pediatric hematologist at the University of Illinois at Chicago. These obstructions are immensely painful, and repeated bouts cause cumulative damage to the body, which is why people with sickle cell die some 20 years younger on average.

    Not everyone with the sickle-cell mutation gets quite so sick. As far back as the 1940s, a doctor noticed that the blood of newborns with sickle-cell disease did not, surprisingly, sickle very much. Babies in the womb actually make a fetal version of the hemoglobin protein, whose higher affinity for oxygen pulls the molecule out of their mother’s blood. At birth, a gene that encodes fetal hemoglobin begins to turn off. But adults do sometimes still make varying amounts of fetal hemoglobin, and the more they make, scientists observed, the milder their sickle-cell disease, as though fetal hemoglobin had stepped in to replace the faulty adult version. Geneticists eventually figured out the exact series of switches our cells use to turn fetal hemoglobin on and off. But there, they remained stuck: They had no way to flip the switch themselves.

    Then came CRISPR. The basic technology is a pair of genetic scissors that makes fairly precise cuts to DNA. CRISPR is not currently capable of fixing the A-to-T typo responsible for sickle cell, but it can be programmed to disable the switch suppressing fetal hemoglobin, turning it back on. Snip snip snip in billions of blood cells, and the result is blood that behaves like typical blood.

    Sickle cell was a “very obvious” target for CRISPR from the start, says Haydar Frangoul, a hematologist at the Sarah Cannon Research Institute in Nashville, who treated Gray in the trial. Scientists already knew the genetic edits necessary to reverse the disease. Sickle cell also has the advantage of affecting blood cells, which can be selectively removed from the body and gene-edited in the controlled environment of a lab. Patients, meanwhile, receive chemotherapy to kill the blood-producing cells in their bone marrow before the CRISPR-edited ones are infused back into their body, where they slowly take root and replicate over many months.

    It is a long, grueling process, akin to a bone-marrow transplant with one’s own edited cells. A bone-marrow transplant from a donor is the one way doctors can currently cure sickle-cell disease, but it comes with the challenge of finding a matched donor and the risks of an immune complication called graft-versus-host disease. Using CRISPR to edit a patient’s own cells eliminates both obstacles. (A second gene-based therapy, using a more traditional engineered-virus technique to insert a modified adult hemoglobin gene into DNA semi-randomly, is also expected to receive FDA approval  for sickle-cell disease soon. It seems to be equally effective at preventing pain crises so far, but development of the CRISPR therapy took much less time.)

    In another way, though, sickle-cell disease is an unexpected front-runner in the race to commercialize CRISPR. Despite being one of the most common genetic diseases in the world, it has long been overlooked because of whom it affects: Globally, the overwhelming majority of sickle-cell patients live in sub-Saharan Africa. In the U.S., about 90 percent are of African descent, a group that faces discrimination in health care. When Gray, who is Black, needed powerful painkillers, she would be dismissed as an addict seeking drugs rather than a patient in crisis—a common story among sickle-cell patients.

    For decades, treatment for the disease lagged too. Sickle-cell disease has been known to Western medicine since 1910, but the first drug did not become available until 1998, points out Vence Bonham, a researcher at the National Human Genome Research Institute who studies health disparities. In 2017, Bonham began convening focus groups to ask sickle-cell patients about CRISPR. Many were hopeful, but some had misgivings because of the history of experimentation on Black people in the U.S. Gray, for her part, has said she never would have agreed to the experimental protocol had she been offered it at one of the hospitals that had treated her poorly. Several researchers told me they hoped the sickle-cell therapy would make a different kind of history: A community that has been marginalized in medicine is the first in line to benefit from CRISPR.

    Doctors aren’t willing to call it an outright “cure” yet. The long-term durability and safety of gene editing are still unknown, and although the therapy virtually eliminated pain crises, Hsu says that organ damage can accumulate even without acute pain. Does gene editing prevent all that organ damage too? Vertex, the company that makes the therapy, plans to monitor patients for 15 years.

    Still, the short-term impact on patients’ lives is profound. “We wouldn’t have dreamed about this even five, 10 years ago,” says Martin Steinberg, a hematologist at Boston University who also sits on the steering committee for Vertex. He thought it might ameliorate the pain crises, but to eliminate them almost entirely? It looks pretty damn close to a cure.

    In the future, however, Steinberg suspects that this currently cutting-edge therapy will seem like only a “crude attempt.” The long, painful process necessary to kill unedited blood cells makes it inaccessible for patients who cannot take months out of their life to move near the limited number of transplant centers in the U.S.—and inaccessible to patients living with sickle-cell disease in developing countries. The field is already looking at techniques that can edit cells right inside the body, a milestone recently achieved in the liver during a CRISPR trial to lower cholesterol. Scientists are also developing versions of CRISPR that are more sophisticated than a pair of genetic scissors—for example, ones that can paste sequences of DNA or edit a single letter at a time. Doctors could one day correct the underlying mutation that causes sickle-cell disease directly.

    Such breakthroughs would open CRISPR up to treating diseases that are out of reach today, either because we can’t get CRISPR into the necessary cells or because the edit is too complex. “I get emails now daily from families all over the world asking, ‘My son or my loved one has this disease. Can CRISPR fix it?’” says Frangoul, who has become known as the first doctor to infuse a sickle-cell patient in a CRISPR trial. The answer, usually, is not yet. But clinical trials are already under way to test CRISPR in treating cancer, diabetes, HIV, urinary tract infections, hereditary angioedema, and more. We have opened the book on CRISPR gene editing, Frangoul told me, but this is not the final chapter. We may still be writing the very first.

    Sarah Zhang

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  • The Future of Obesity Drugs Just Got Way More Real

    The Future of Obesity Drugs Just Got Way More Real

    A wild idea recently circulated about the future of aviation: If passengers lose weight via obesity drugs, airlines could potentially cut down on fuel costs. In September, analysts at Jefferies Bank estimated that in the “slimmer society” obesity drugs will create, United Airlines could save up to $80 million in jet fuel annually.

    In the past year, as more Americans have learned about semaglutide, which is sold for diabetes under the brand name Ozempic and for obesity under the name Wegovy, hype has become completely divorced from reality. For all the grand predictions, just a fraction of Americans who qualify for obesity drugs are on them. With a list price of roughly $1,350 a month, Wegovy is far too expensive, under-covered by insurance, and in limited supply to be a routine part of health care.

    But that possibility is beginning to seem very real. The results of a highly anticipated study published on Saturday indicate that Wegovy can have profound effects on heart health, which potentially opens up the drug to even more patients. A few days earlier, the FDA approved Zepbound, an obesity drug that is a bit cheaper and appears more potent than Wegovy. If there was any doubt before, now it is undeniable: Obesity drugs “are here to stay,” Kyla Lara-Breitinger, a cardiologist at the Mayo Clinic, told me. “There’s only going to be more and more of them.” They are now poised to become deeply entrenched in American health care, perhaps eventually even joining the ranks of commonly used drugs such as statins and metformin.

    Considering that obesity is linked to all sorts of major heart ailments, it is no big surprise that a weekly shot for weight loss might have some cardiovascular benefits. But because this class of obesity drugs, known as GLP-1 agonists for the hunger hormone they target, is so new, doctors did not know that for sure. Starting in 2018, Novo Nordisk, the company that manufactures semaglutide, began to look for answers in a study of more than 17,600 people with obesity and cardiovascular disease. In this group, results of a trial named SELECT show that Wegovy reduced the risk of major cardiac events—stroke, heart attack, death—by 20 percent. Even compared with studies on common heart medications such as Praluent and Repatha, the Wegovy results are “impressive,” Eugene Yang, a cardiologist and professor of medicine at the University of Washington, told me.

    How exactly the drug prevents major cardiac events isn’t fully understood. Some of the effects can likely be chalked up to weight loss itself, which is associated with improvements in metrics that influence heart health, such as blood pressure, Yang said. But mechanisms independent of weight loss may also be at work. In the trial, lower rates of cardiovascular events began showing up before participants lost weight. One explanation is the drug’s impact on inflammation, which is associated with heart disease: C-reactive protein, a rough proxy for inflammation, dropped by nearly 40 percent in study participants.

    Regardless of how Wegovy works, Yang said, “it has the potential benefit of being very significant” as a new line of treatment for heart disease, the leading cause of death nationwide. Novo Nordisk has already applied for expanded FDA approval and anticipates receiving it within six months. Approval would also show that Wegovy has a medical benefit beyond weight loss, pressuring insurers to cover it. Right now, for instance, Medicare does not, in part because obesity has long been viewed as a cosmetic issue, not a medical one. Even with private coverage, the drug is still frequently out of reach. The SELECT trial makes it “unequivocally clear” that obesity is a health condition that can be treated with drugs, Ted Kyle, an obesity-policy expert, told me. Still, the study leaves room for pushback: The absolute risk reduction of cardiovascular events was 1.5 percent, which is, by some reckonings, quite small. A higher risk reduction would have “put more pressure” on insurers and manufacturers to make the drugs more affordable for Americans, Lara-Breitinger said.

    Still, the findings are robust enough that it seems likely that the heart benefits of obesity drugs will lead more Americans to take them—if not immediately, then eventually. The approval of a new drug could do the same. Tirzepatide, which Eli Lilly has sold as a diabetes drug under the name Mounjaro, will be marketed as Zepbound for obesity—and it is coming for Wegovy’s throne. In one study, people on tirzepatide lost an average of 18 percent of their body weight; for comparison, in another study patients on Wegovy lost an average of 15 percent. At a little over $1,000 a month, Zepbound is not cheap, but its list price is hundreds of dollars lower than that of Wegovy. (The manufacturers of both drugs have said that most insured patients pay far less than that.)

    Zepbound’s approval is just the beginning. Unlike semaglutide, which targets only one hormone, GLP-1, to exert its effects on appetite and fullness, tirzepatide targets two. Other drugs that target two or even three hormones are in the works, as are versions that come in a more appealing pill format rather than as an injection. Generic versions of these drugs, likely beginning with liraglutide, a predecessor to semaglutide sold as Saxenda, could become available soon, Yang said. This competition will help bring down costs, but it will go only so far. Drug pricing is “a little bit screwy,” Kyle said, complicated by the wide gap between the list price and the net price created by manufactures, insurers, and intermediaries between them.

    Each new competitor and new study is a step toward a future in which a substantial proportion of Americans with obesity are routinely prescribed these drugs. In a single week, obesity drugs leapt a new era—one in which they are about to become significantly more mainstream. No doubt that future is a bright one for millions of people who might benefit from treatment. Still, many questions about the drugs remain unanswered, such as their long-term safety and endless supply shortages.

    But the potential for obesity drugs to truly change America has never felt closer—with all of the dizzying questions this creates about what “a slimming society” might mean for exercise, the food industry, and apparently even airline jet fuel.

    Yasmin Tayag

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  • We Can Finally Do Something About the Third ‘Tripledemic’ Virus

    We Can Finally Do Something About the Third ‘Tripledemic’ Virus

    Every fall, when the air turns chilly and the leaves red, pediatric ICUs begin preparing for the onslaught of the virus known as RSV. Not flu, not COVID, but RSV, or respiratory syncytial virus, is the No. 1 reason babies are hospitalized, year after year. Their tiny airways can become inflamed, and the sickest ones struggle to breathe. RSV is deadly on the other end of the age spectrum too, killing 6,000 to 10,000 elderly Americans every year.

    For decades though, there was no way to stop the virus’s seasonal tide. The quest for a vaccine always came up short. And then suddenly, the vaccines started working.

    This year, doctors have not just one but multiple new shots to prevent RSV. Three gained FDA approval in rapid succession in recent months: an antibody shot for infants called nirsevimab, a form of passive immunization for babies too young to get proper vaccines; a vaccine from Pfizer for both adults over 60 and pregnant mothers, who can pass the immunity on to their babies; and finally, a vaccine from GlaxoSmithKline also aimed at adults older than 60. Together, these herald a new era for RSV.

    That these three new RSV shots are coming out at once is no coincidence. They succeed where others failed because they all target a specific weak spot in the virus, first identified in 2013. This strategy of finding a virus’s most vulnerable points applies to other pathogens too, and experts say it can revolutionize the design of vaccines for other diseases. In fact, it was quietly used to make the COVID vaccines from Pfizer and Moderna. Scientists had originally perfected the idea with RSV, only to repurpose it for the COVID vaccine, which raced ahead, given the urgency of the pandemic. This year, though, the shots are coming for RSV.

    “We’re in a really good position, finally, after more than 65 years,” says Asunción Mejías, an infectious-diseases doctor at St. Jude Children’s Research Hospital.

    The first attempts to make an RSV vaccine began not long after the virus’s discovery, in 1956, but an early trial ended so catastrophically that it had a chilling effect for decades.

    It had started off with promise. The early vaccine was modeled after a successful one for polio, in which the virus is inactivated with a chemical called formalin. But when infants given the early RSV vaccine later caught the virus, a whopping 80 percent had to be hospitalized—compared with only 5 percent in the control group. Two of the babies died, their lungs ravaged. The vaccine did worse than offer no protection; it made the disease more severe. “It was such a disaster,” says Ann Falsey, an infectious-diseases doctor at the University of Rochester. Scientists spent years piecing together why—the vaccine riled up the wrong part of the immune system in very young babies—but they got no closer to making a vaccine that worked. The field was stuck.

    Then, in 2008, a serendipitous meeting led to an eventual breakthrough. A young, freshly minted Ph.D. named Jason McLellan, who studies the structure of proteins, began a new job at the National Institutes of Health to work on HIV vaccines. The lab he had joined, on the fourth floor, had run out of room, though, so he got put in another, on the second. There, he ran into Barney Graham, a virologist who had been trying to solve the puzzle of RSV since the 1980s. He convinced McLellan that this virus was worth a look too.

    By then, scientists had at least homed in on a plausible vaccine target. Much as COVID uses spike protein to infect cells, RSV uses a protein—called F for “fusion”—to physically fuse the virus particle to a human cell. F comes in two forms, though: an extremely unstable prefusion state and a far more stable postfusion state. And once it switches to the postfusion state—which can also happen spontaneously— “it can’t come back,” McLellan told me.

    When RSV vaccines are manufactured, all the F protein eventually switches to the postfusion state. But the antibodies against postfusion F weren’t very effective. McLellan soon figured out why. He found that extremely potent neutralizing antibodies bind to a specific site—the very tip of the prefusion F—that is lost when the protein rearranges into its postfusion form. With that, Graham told me, “you lose ten- to 1,000-fold potency.” An effective RSV vaccine would need to target the prefusion F.

    The team knew what to do, but had a practical dilemma: How to stabilize F in its prefusion form, so the team could put it in a vaccine? McLellan rejiggered the protein slightly, adding molecular “staples” and filling a hole in the protein structure. These changes froze F in its prefusion shape. When the team tested this version of the vaccine in mice, the results could not have been clearer. The vaccine induced the highest levels of neutralizing antibodies Graham had ever seen in his three decades of studying RSV. “This is it,” McLellan remembers thinking.

    Soon, pharmaceutical companies came calling, and the race was on. (The experts in this article—like nearly everyone who works on RSV vaccines—have all received research grants, consulted for, or worked in some other way with one or more of the companies developing shots for RSV.) Today, Pfizer’s and GlaxoSmithKline’s newly approved RSV vaccines target the prefusion F protein, as does nirsevimab, the antibody shot for infants from AstraZeneca and Sanofi. Both the vaccines and the antibody shot trigger immunity against RSV: Vaccines stimulate the immune system to make its own antibodies, and nirsevimab is a direct infusion of antibodies.

    Trials for all three shots were already under way when the coronavirus pandemic hit. But because RSV nearly disappeared during social distancing, the trials got delayed. Meanwhile, McLellan and Graham devised a similar molecular trick to stabilize COVID’s spike protein, which Pfizer and Moderna later used in their vaccines. (The stabilization wasn’t make-or-break for COVID, as it was for RSV, though—AstraZeneca’s COVID vaccine was effective despite not having this modification.) But unstable fusion proteins are found in many different classes of viruses beyond RSV. McLellan, now at the University of Texas at Austin, is working on shots against the prefusion structure of other stubborn viruses such as cytomegalovirus and Crimean-Congo hemorrhagic fever. (Graham is now a professor at Morehouse School of Medicine.) This approach—called structure-based vaccine design—could unlock new ways of targeting once-elusive viruses.

    For RSV, this fall and winter will be a test of how well the shots fare in the real world. As the adage goes, vaccines don’t save lives; vaccinations do. Falsey, the University of Rochester doctor, specializes in studying RSV in the elderly, and she worries that too few Americans over 60 will get the new vaccines this year. A CDC advisory panel decided that elderly Americans can get the vaccines through “shared clinical decision-making” with their doctors but did not go as far as to fully recommend vaccination, which would have triggered private insurers to cover the shots under the Affordable Care Act. Out of pocket, they can cost more than $300. The vaccine for pregnant women, meanwhile, has FDA approval, but the same CDC panel is voting today on whether to recommend it. The panel will likely scrutinize a possible link to premature births, which has shown up before with RSV vaccines.

    Nirsevimab, the antibody shot for infants, has gotten a full-throated endorsement, though, and it’s poised to have the biggest impact this season. It replaces an existing RSV-antibody shot called palivizumab, which is not widely used. Palivizumab targets a less potent site that is on both the pre- and postfusion F, and it needs to be administered up to five times a season (compared with once for nirsevimab), at a cost of some $1,500 a dose. For these reasons, it’s been reserved for the highest-risk babies, such as preemies with underdeveloped lungs. But most babies who end up hospitalized were healthy to begin with, says St. Jude’s Mejías, so the older shot didn’t put much of a dent in overall hospitalizations.

    Nirsevimab is meant to be more widely used: The shot is approved for all infants in their first RSV season. “It’s going to change the way we manage and treat RSV,” Mejías told me. It should be available for babies starting in October. And if all goes according to plan, pediatric ICUs could be a little quieter this winter.

    Sarah Zhang

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