Tag: Drugs (Pharmaceuticals)

How an Unproven Alzheimer’s Drug Got Approved

Though some of its own senior officials said there was little evidence of benefit for patients, the F.D.A. nonetheless greenlighted Biogen’s Aduhelm, or aducanumab.

Many Alzheimer’s Experts Say Use of Aduhelm Should Be Sharply Limited

Even those who supported the F.D.A.’s approval of the controversial new drug said authorizing it for anyone with Alzheimer’s disease was much too broad.

A new drug for the treatment of Alzheimer’s disease should be given to a much narrower group of patients than the federal approval permits, Alzheimer’s experts — including those who strongly supported approval of the medication — said on Monday.

Since the Food and Drug Administration approved the controversial and expensive drug, Aduhelm, made by Biogen, this month, much discussion has focused on the fact that many scientists, and the F.D.A.’s own independent advisory committee, say the evidence does not convincingly show that the drug works.

But another major issue has received less attention: which patients should receive the drug and what doctors should do to prescribe it responsibly and safely.

The F.D.A. has so far imposed strikingly few limitations on Aduhelm, a monthly intravenous infusion that requires patients to have regular M.R.I. scans because the drug can cause swelling or hemorrhaging in the brain.

While the only patients who received the drug during clinical trials were those with very mild Alzheimer’s or an even milder pre-Alzheimer’s impairment, the F.D.A.’s label for Aduhelm says simply that the drug is “for the treatment of Alzheimer’s disease.” Under “contraindications,” the term for health conditions or other characteristics that should prevent patients from taking a drug, the label says “None.”

The broadness of the label has surprised and concerned even the biggest champions of the drug.

“Oy,” said one enthusiastic supporter of Aduhelm’s approval, Dr. Stephen Salloway, describing his reaction “when I saw from the label that there are no contraindications.”

Dr. Salloway, director of neurology and the Memory and Aging Program at Butler Hospital in Providence, R.I., spoke on Monday in a forum sponsored by the Alzheimer’s Association, a large patient advocacy group that pushed for approval of the drug. He and the five other experts answering questions about the use of the drug emphasized that the use of Aduhelm should be limited to certain patients: those in early stages of the disease whose brains contain high levels of amyloid, a protein that clumps into plaques in people with Alzheimer’s disease.

The panelists, who had varying opinions about whether Aduhelm should have been approved, agreed that the drug’s potential brain side effects must be monitored carefully and that doctors should disclose to interested patients that there are many unknowns about Aduhelm, including whether it can provide any benefit.

Aduhelm was designed to slow the progression of memory and thinking problems in people with mild cognitive symptoms, but its approval has been contentious. A number of scientists objected because only one of two clinical trials showed any hint of benefit, and in that trial the high dose of the medication slowed cognitive decline only slightly — by about four months in an 18-month period.

Dr. Salloway, a site principal investigator for trials of the drug, wasn’t paid for that work but has received research and consulting fees from Biogen. He said doctors should use the drug only for patients whose statuses match those in the clinical trials.

“There’s no evidence that it could be beneficial for any other stage of Alzheimer’s,” he said.

Mary Sano, director of the Mount Sinai Alzheimer’s Disease Research Center in New York City, said the criteria that she and other panelists outlined were “very important” and meant that “it’s going to be very restrictive and the ability to share this drug with a wide range of people will be significantly limited, at least at this time.”

Treating people only with mild symptoms would mean that for dementia clinicians, “most of your people in your current practice are probably not eligible,” Dr. Sano said.

In its decision, the F.D.A. acknowledged that there was not the level of evidence of benefit that the agency usually requires. As a result, it is making Aduhelm available under a program called accelerated approval, citing the drug’s ability to reduce levels of amyloid in the brain. But reducing amyloid is not the same thing as slowing symptoms of dementia. Many amyloid-reducing drugs have failed to slow decline in clinical trials, a history that makes some experts especially wary of placing confidence in Aduhelm based on the evidence produced so far.

Given the agency’s emphasis on amyloid in its approval decision, and the fact that all of the clinical trial participants had to have high amyloid levels, experts have also been surprised that the F.D.A. label does not require patients to be screened for the protein. Doctors at the Alzheimer’s Association forum all said that high levels of amyloid, typically measured by PET scan or spinal tap, should be a condition of treatment.

Several of the panelists said that, at least at the outset, relatively few doctors and clinics would have the ability to adequately diagnose, screen and treat patients.

“This is not a simple medication to use,” said Dr. Paul Aisen, director of the Alzheimer’s Therapeutic Research Institute at the University of Southern California and a co-author of an article that urged the F.D.A. to approve the drug. “I think that establishing the appropriate individuals for treatment, and monitoring treatment, requires knowledge and benefits from experience, and there are very few clinicians who have this experience.”

The panelists devoted considerable discussion to the possibility of brain swelling and hemorrhages, which occurred in about 40 percent of participants who received the high dose in the two large clinical trials. Many cases were mild or asymptomatic, but Dr. Alireza Atri, director of the Banner Sun Health Research Institute in Phoenix and another co-author of the article supporting approval of the drug, said that it was possible that “one out of 200 or 300 individuals can have a serious side effect and need to be in a hospital.”

Dr. Salloway said that it would be “more challenging” for doctors to safely monitor for brain side effects than it was within the strict standards of the clinical trials. He said that people should not be given the drug if they have had a macro-hemorrhage in the brain; more than five micro-hemorrhages; a significant stroke; or “unstable medical conditions that could interfere with treatment.”

Dr. David S. Knopman, a clinical neurologist at the Mayo Clinic and a site principal investigator for one of the trials, who did not support approval, said people who were taking blood thinners should also be excluded.

“We know that this treatment carries considerable risks,” said Suzanne Craft, co-director of the Roena B. Kulynych Center for Memory and Cognition Research at the Wake Forest University School of Medicine. And assessing how and whether it helps patients could be tricky, Dr. Craft and others said.

It will be important to have comprehensive discussions with patients and families about “how to weigh the inconvenience and cost and risk against the possible benefit,” Dr. Aisen said.

“Managing expectations is a huge challenge here,” he said, adding that “our expectation is a modest slowing of the rate of decline. It is impossible to determine on an individual patient level whether someone is benefiting or not.”

Desperate for Covid Care, Undocumented Immigrants Resort to Unproven Drugs

Shut out from mainstream medicine, some immigrants are buying expensive, unproven Covid therapies from “wellness” clinics or turning to the black market.

FRESNO, Calif. — On a Tuesday afternoon in April, among tables of vegetables, clothes and telephone chargers at Fresno’s biggest outdoor flea market were prescription drugs being sold as treatments for Covid.

Vendors sold $25 injections of the steroid dexamethasone, several kinds of antibiotics and the anti-parasitic drug ivermectin. Chloroquine and hydroxychloroquine — the malaria drugs pushed by President Donald J. Trump last year — make regular appearances at the market as well, as do sham herbal supplements.

Health and consumer protection agencies have repeatedly warned that several of these treatments, as well as vitamin infusions and expensive injections of “peptide therapies” sold at alternative wellness clinics for more than $1,000, are not supported by reliable scientific evidence.

But such unproven remedies, often promoted by doctors and companies on social media, have appealed to many people in low-income immigrant communities in places across the country where Covid-19 rates have been high but access to health care is low. Some turn to unregulated drugs because mainstream medicine is too expensive or is inaccessible because of language or cultural barriers.

“It’s disappointing but not surprising” that people living below the poverty line have spent large sums of money for unproven treatments for Covid-19, said Rais Vohra, the interim head of Fresno County’s health department. “People are desperate and bombarded with misinformation and may not have the skills, time or context to interpret medical evidence.”

The trend is not new. In 2014, Dr. Vohra published a case report on a Hmong woman who showed up at an emergency room in Fresno with life-threatening poisoning after overdosing on chloroquine that she had bought at the flea market under the label “red Tylenol.” He and his colleagues subsequently went to the market and to three smaller shops and found 35 different medications that were prescription-only or had been deemed unsafe by the Food and Drug Administration. “It was a real eye opener,” he said.

Oralia Maceda Méndez, an advocate at a Fresno-based community group for Indigenous people from Oaxaca, Mexico, said those in her community feared that “the government might be trying to get rid of us.”
Oralia Maceda Méndez, an advocate at a Fresno-based community group for Indigenous people from Oaxaca, Mexico, said those in her community feared that “the government might be trying to get rid of us.”Brian L. Frank for The New York Times

During the pandemic, many immigrants shut out of mainstream health care have turned to such markets for Covid-19 treatments. About 20 percent of Hispanic people in the United States lack health insurance, and the proportion is far higher among undocumented immigrants.

What’s more, some immigrants mistrust doctors who don’t speak their language or who treat them curtly — and those concerns have been amplified by harsh political rhetoric directed at Mexicans and Central Americans.

“My community fears that the government might be trying to get rid of us,” said Oralia Maceda Méndez, an advocate at a Fresno-based community group for Indigenous people from Oaxaca, Mexico. She has heard many stories from immigrants in her community who treat themselves for Covid-19 with penicillin, other antibiotics or a mix of vitamins and herbal therapies bought from shops or travelers selling medications bought in Mexico.

“I am not surprised that people are taken advantage of,” she said. “We don’t have the care we need.”

Some farmworkers have received unproven treatments at specialty clinics. A woman in Fresno recently described how her husband, a farmworker, had fallen so sick from Covid-19 that he couldn’t breathe or walk, but he refused to go to the hospital because he had heard rumors that undocumented immigrants had checked in and never left. She took him to a wellness clinic, where a doctor gave him injectable peptide treatments, recalled the woman, who requested anonymity because of her immigration status.

She wasn’t prepared, she said, for the $1,400 bill, which included the cost of syringes and vials labeled thymosin-alpha 1, BPC-157 and LL-37. Pulling them out of a cabinet in the kitchen of her mobile home, she said she didn’t know exactly what they were, and she still feels the sting of the price.

“I was shocked, but I was trying to act like it was OK because I had to be strong for my husband and my kids,” she said. He grew sicker despite the injections, but the family had no funds left for care. More than a month passed before he was well enough to return to the fields.

Sandra Celedon, the president of a coalition of grass-roots organizations called Fresno Building Health Communities, said she and her colleagues have heard from several farmworkers and other low-income Latino immigrants who spent their savings on vitamin infusions and peptide therapies for Covid. “These folks are the poorest of the poor, and yet the doctors were requesting cash for their unproven treatments,” she said.

Sandra Celedon, a leader of a coalition of grassroots organizations in Fresno, knows of several low-income immigrants who spent their savings on vitamin infusions and peptide therapies for Covid.Brian L. Frank for The New York Times

Some unregulated drugs can be dangerous. And even if they aren’t a health risk by themselves, they can lead people to postpone seeking help from doctors, which can be deadly. Delayed treatment is one reason Black and Hispanic people have died from Covid at twice the rate as white people in the United States.

Alternative therapies can also limit a patient’s treatment options because doctors worry about toxic drug interactions, said Dr. Kathleen Page, an infectious-disease specialist at Johns Hopkins University School of Medicine in Baltimore.

Undocumented immigrants from Mexico and Central America who have gone to the emergency room at her hospital often mention home remedies, vitamins or antibiotics they have injected or ingested before seeking care. “I’m not upset at patients when they tell me what they’ve taken,” Dr. Page said. “I’m upset about the system that makes it easier for them to get help from nontraditional places than from regular health care.”

Unable or unwilling to talk with mainstream medical providers, some people turn instead to Facebook, YouTube or WhatsApp for advice. On Covid-19 Recipes and Home Remedies, for example, a Facebook page in Spanish that has about 10,000 members, people from the United States, Mexico and South America exchange tips on herbal concoctions, zinc, vitamin B12, ivermectin and chlorine dioxide — which has been tied to reports of respiratory and liver failure.

Dr. Ignacio Guzman, who specializes in “anti-aging, regenerative and integrative medicine” at a clinic in an affluent area of northern Fresno, uses social media to advertise peptide therapy for a broad range of ailments. On Instagram, he promoted it in a photograph of himself getting a Covid-19 vaccine, writing that “integrating peptides with immunizations can double their efficacy!” (No clinical trials of Covid-19 vaccines support that claim, and the shots are highly effective on their own.)

Another Instagram post, from March 2020, includes a photograph showing an intravenous line in the doctor’s arm above a caption in which he indicates that he is being infused with vitamin C. “This IV along with peptide therapy will limit my chances of acquiring infections such as Influenza A and the Corona Virus!” he wrote.

The Fresno flea marketBrian L. Frank for The New York Times

The F.D.A. points out that the thymosin-alpha 1 peptide therapy is not authorized in the United States to treat Covid-19, nor is it approved for any other condition. Over the past year, that agency and the Federal Trade Commission have cracked down on hundreds of companies making unsupported claims about supposed Covid-19 treatments, including thymosin-alpha 1, BPC-157 and vitamin C infusions. The F.T.C. warns that anyone who makes “deceptive claims related to the treatment, cure, or prevention of Covid-19” could be subject to penalties of up to $43,792 for each violation.

Neither of those agencies has sent a public warning letter to Dr. Guzman. He and his lawyer did not respond to several requests for comment.

Dr. Juan G. Bautista, who works with Dr. Guzman at the clinic, declined to comment on his colleague. “I don’t want to speak against another doctor if their intention was to take care of a patient,” he said.

When Dr. Bautista came down with Covid-19 himself last year, he tried peptides, along with a host of standard treatments. He said that he hadn’t used peptides to treat Covid-19 in his patients but that he didn’t fault doctors who had used experimental therapies that they believed could help people recover from a never-before-seen virus.

“Physicians were doing everything possible to keep patients outside of the hospital,” he said, citing the distress of intubation and medical bills that could wipe out the savings of his low-income patients from Fresno and the broader San Joaquin Valley. “There’s not a lot of people here in the Valley that take care of the poor.”

Sandy Sirias contributed reporting. This story was supported by the Pulitzer Center.

Looking to Tackle Prescription Overload

Older adults often take more medications than they need, or than is safe. Increasingly, geriatric experts and their patients are exploring the benefits of “deprescribing.”

The last straw, for Leslie Hawkins, was her mother’s 93rd-birthday gathering in 2018.

Her mother, Mary E. Harrison, had long contended with multiple health problems, including diabetes and the nerve pain it can cause; hypertension; anxiety; and some cognitive decline. She was prone to falling.

Still, she had been a sociable, churchgoing nonagenarian until Ms. Hawkins, who cared for her in their shared home in Takoma Park, Md., began seeing disturbing changes.

“She was out of it,” recalled Ms. Hawkins, 57. “She couldn’t hold a conversation or even finish a sentence.” On her mother’s birthday, she said, “A bunch of us went to Olive Garden, and Mommy sat there asleep, slumped over in her wheelchair. I decided, nope.”

Ms. Hawkins and one of her brothers took their mother to see a geriatrician at Johns Hopkins Hospital, where she could supply only three correct answers on the 30-question test commonly used to assess dementia. “She didn’t really participate,” said the geriatrician, Dr. Stephanie Nothelle.

Fortunately, Ms. Hawkins had brought a list of the 14 medications Ms. Harrison was taking, several of which alarmed her new doctor. “I started chipping away at them,” Dr. Nothelle said.

She recommended stopping oxybutynin, prescribed to treat an overactive bladder, because “it’s notorious for precipitating delirium and causing confusion in older adults,” she said. She also suggested eliminating the pain medication Tramadol, which has similar effects and contributes to unsteadiness and falls.

At their next visit in three months, Dr. Nothelle told the family, they would discuss stopping several more drugs, including gabapentin for neuropathy; a diabetes medication that lowered Ms. Harrison’s blood sugar to unnecessary levels; and a reflux drug that nobody could remember her needing.

The follow-up visit did not happen as scheduled. Ms. Harrison fell and broke her hip, requiring surgery and six weeks in rehab.

Still, her daughter had gotten the message: Her mother’s many drugs might be harming her. “I went online and looked everything up and I started questioning her doctors,” Ms. Hawkins said.

Fourteen prescriptions? “Unfortunately, that’s pretty common” for older patients, Dr. Nothelle said. The phenomenon is called polypharmacy, sometimes defined as taking five or more medications, as two-thirds of older people do.

More broadly, polypharmacy refers to an increasing overload of drugs that may not benefit the patient or interact well with one another, and that may cause harm including falls, cognitive impairment, hospitalization and death. It has sparked interest in “deprescribing”: the practice in which doctors and patients regularly review medication regimens to prune away risky or unnecessary drugs.

For older patients, the most commonly prescribed inappropriate medicines include proton pump inhibitors like Nexium and Prilosec, benzodiazepines like Xanax and Ativan, and tricyclic antidepressants, according to an analysis of Medicare data published last year. Over-the-counter products and supplements can also prove problematic.

“We spend hundreds of millions every year to bring meds to market and figure out when to start using them, and next to nothing trying to figure out when to stop them,” said Dr. Caleb Alexander, an internist and epidemiologist at the Johns Hopkins University School of Medicine. Yet among older people, adverse drug reactions account for one in 11 hospital admissions.

Ms. Hawkins began investigating the various drugs her mother was on. “I went online and looked everything up and I started questioning her doctors,” she said.Rosem Morton for The New York Times
With her daughter’s help and a new doctor, Ms. Harrison has reduced her number of medications, and she is now getting physical therapy to improve her mobility.Rosem Morton for The New York Times
Ms. Hawkins with a box of her mother’s medications. Her mother’s new doctor helped her prune her medications to four drugs, from 14.
Ms. Hawkins with a box of her mother’s medications. Her mother’s new doctor helped her prune her medications to four drugs, from 14.Rosem Morton for The New York Times

Hence the Drive to Deprescribe campaign, launched last month by the Society for Post-Acute and Long-Term Care Medicine, known as AMDA, which represents medical directors and administrators of long-term care facilities, where polypharmacy is particularly prevalent.

The initiative calls for a 25 percent reduction in medication use within a year, with AMDA monitoring the results. “An ambitious goal,” said Dr. Sabine von Preyss-Friedman, co-chair of the Drive to Deprescribe work group. “But if you do a little here and a little there, you don’t move the needle.”

To date, 2,000 facilities have enrolled, along with three major consulting pharmacies that serve them. That represents a fraction of the nation’s 15,000 nursing homes, with several large chains unrepresented, but “we are still recruiting,” Dr. von Preyss-Friedman said.

Another milestone in the polypharmacy battle: the U.S. Deprescribing Research Network, established in 2019 and funded by the National Institute on Aging. So far, it has awarded nine grants to test effective deprescribing strategies.

“Stopping a medication is not just the reverse of starting one,” said Dr. Michael Steinman, a geriatrician at the University of California, San Francisco, and co-director of the network. “It’s often much harder.”

The barriers reflect a fragmented health care system, in which a patient’s endocrinologist, for example, pays scant attention to what her cardiologist or neurologist has prescribed, while her primary care doctor hesitates to overrule any of them.

Deprescribing discussions also require time, a luxury during a brief office visit with a senior who may have many competing needs.

“There’s a general bias toward doing things in medicine,” said Dr. Ariel Green, a geriatrician and researcher at Johns Hopkins. “If we prescribe something, that’s seen as a positive action. If we stop something, or don’t start it, that’s not.”

So inertia can easily take over, with prescriptions being refilled year after year without anyone exploring why they were initially written, whether one drug duplicates another or whether the medications remain necessary or effective.

Most older adults say they are willing to reduce their medications, according to a 2018 study published in JAMA Internal Medicine — yet paradoxically, participants also said that all their medications were necessary.

Seniors may resist deprescribing, unwilling to see a drug routine they have been accustomed to for years as dangerous. “How do we talk about taking fewer medications without it looking like we’re withdrawing care, or like the person isn’t worthy of treatment?” Dr. Green said. Her own studies indicate that older patients respond well to discussions focusing on drugs’ possible side effects.

A dispiriting number of interventions aimed at deprescribing have had little impact, according to a review of 38 studies published last year. But one recent Canadian clinical trial showed significant results.

The study enlisted pharmacists, who handed or mailed patients a deprescribing brochure before refilling certain risky prescriptions. The pharmacists also contacted the prescribing doctors with forms explaining why the drugs might be harmful, providing safer alternatives and allowing doctors to change or eliminate prescriptions by simply checking a box.

Although Ms. Harrison still needs assistance, her condition has vastly improved over the last two years, and she scored far better on a cognition test. “It was night and day,” her doctor said.Rosem Morton for The New York Times

Within six months, 43 percent of those using sedative-hypnotic drugs (benzodiazepines and the related “Z-drugs” like Ambien) were able to discontinue them. So were 30 percent of the patients using the older diabetes drug glyburide and 57 percent of those using nonsteroidal anti-inflammatories, or NSAIDs.

“It was spectacular,” said Dr. Cara Tannenbaum, a geriatrician at the University of Montreal and senior author of the study. Now, she added, “How do we scale it up and get it out of research projects and into everyday practice?”

One way is for patients themselves to combat polypharmacy, by regularly asking their doctors to reassess their medications — sometimes bringing every pill bottle, including supplements, to an appointment for a “brown bag review.” A short list of potentially inappropriate drugs, published by the American Geriatrics Society, can help them spot problems.

That is essentially what Leslie Hawkins did for her mother, Dr. Nothelle said. “Every time she had a health care interaction, she asked, ‘Do we need this? Can we lower this? Can we stop this?’”

Ten months passed before Ms. Harrison could see her geriatrician again, and by then, “she was a completely different person,” Dr. Nothelle said. “She was awake, she answered my questions. It was night and day.”

Ms. Harrison’s score on the 30-question cognition test jumped from three to 25. She is starting physical therapy to improve her mobility. And she is taking four drugs — insulin, a blood pressure medication and two anti-depressants — instead of 14.

Ms. Harrison, now 95, still needs considerable assistance. But at her 94th-birthday celebration in a downtown Washington, D.C., restaurant, with 20 family members including great-grandchildren, “She was the life of the party,” her daughter said. “We had a ball.”

Alzheimer’s Drug Poses a Dilemma for the F.D.A.

The Food and Drug Administration is on the verge of announcing one of its most contentious decisions in years: the fate of an Alzheimer’s drug that could be the first treatment approved after nearly two decades of failed efforts to find ways to curb the debilitating disease.

On Monday, the agency will rule on the drug, aducanumab, which aims to slow progression of memory and thinking problems early in the disease. If approved, it would be the first new Alzheimer’s medication since 2003 and the first treatment on the market that attacks the disease process rather than just easing symptoms.

It would become a blockbuster drug within several years, analysts predict, costing tens of thousands of dollars annually per patient and bringing a windfall to its manufacturer, Biogen.

Patient groups, desperate for treatments, are pushing for approval. But greenlighting the drug would fly in the face of objections from several prominent Alzheimer’s experts and the F.D.A.’s independent advisory committee.

In November, the committee voted overwhelmingly against recommending approval, saying data failed to demonstrate persuasively that aducanumab slowed cognitive decline. Three advisory committee members later wrote a point-by-point critique of the evidence. Other scientists, and an independent think tank, say aducanumab hadn’t shown convincing benefit to outweigh its safety risks.

“This should not be approved, because substantial evidence of effectiveness hasn’t been shown,” said Dr. Lon Schneider, director of the California Alzheimer’s Disease Center at the University of Southern California and one of many site investigators who helped conduct one of the aducanumab trials. “There’s very little potential that this will address the needs of patients.”

Beyond the status of this particular drug, some experts worry approval could lower standards for future drugs — an especially important question at a time when public trust in science is teetering.

“I simply don’t see a path for approval because of the absence of evidence that’s been shared to date that this product works, and I think it would set a remarkably dangerous precedent — not only for the field of Alzheimer’s research but also for the broader regulation of prescription drugs in our country,” said Dr. G. Caleb Alexander, an F.D.A. advisory committee member and an internist, epidemiologist and drug safety and effectiveness expert at the Johns Hopkins Bloomberg School of Public Health.

About six million people in the United States and roughly 30 million globally have Alzheimer’s, a number expected to double by 2050. Currently, five medications approved in the United States can delay cognitive decline for several months in various Alzheimer’s stages. About two million Americans have mild Alzheimer’s-related impairment, fitting criteria for aducanumab, a monthly intravenous infusion requiring regular imaging to detect potential brain swelling.

Biogen officials declined to comment for this article, but in earnings calls, medical meetings and F.D.A. presentations, they have said the evidence shows cognitive benefit. Several Alzheimer’s experts whose experience includes consulting for Biogen wrote recently that aducanumab “achieves the standard of meaningful efficacy with adequate safety.”

The Biogen headquarters in Cambridge, Mass.
The Biogen headquarters in Cambridge, Mass.Cody O’Loughlin for The New York Times

Debate centers on two never fully completed Phase 3 trials that contradicted each other. One suggested that a high dose could slightly slow cognitive decline; the other showed no benefit. Biogen says that given the need for Alzheimer’s medications, the single positive trial, plus results from a small safety trial and aducanumab’s ability to reduce a key protein, should justify approval.

The F.D.A. typically follows advisory committee recommendations and usually requires two convincing studies for approval, but it has made exceptions, especially for severe diseases that lack treatments.

Two other medications now in trials appear more promising than aducanumab, experts say, but it could be three or four years before data would indicate whether they merit approval. Many families say that’s too long to wait.

“There’s lots of issues with the data,” acknowledged Maria Carrillo, chief science officer for the Alzheimer’s Association, a patient advocacy group campaigning vigorously for approval. But she said her organization must “weigh the crushing reality of what people live with today” and support giving patients something to try instead of waiting several years for more conclusive positive results.

The F.D.A. itself seems divided. In advisory committee presentations, a clinical analyst cited “substantial evidence of effectiveness to support approval.” But an F.D.A. statistician wrote that another trial was needed because “there is no compelling, substantial evidence of treatment effect or disease slowing.”

And some experts, like Dr. Ronald Petersen, director of the Mayo Clinic’s Alzheimer’s Disease Research Center in Rochester, Minn., say they’re “on the fence.” He said he’d like to give patients a new option soon but “the data are iffy.”

Aducanumab, a monoclonal antibody, targets a protein, amyloid, that clumps into plaques in the brains of Alzheimer’s patients. Many amyloid-reducing drugs failed to slow symptoms in trials, a history that, some experts say, makes it especially important that aducanumab’s data be convincing. If effective, it would support a long-held, unproven theory that attacking amyloid can help if done early enough.

Excitement about aducanumab grew after a small early trial to evaluate safety showed amyloid reduction and hinted it might slow cognitive decline. The F.D.A., in a move some experts question, allowed Biogen to skip Phase 2 trials and conduct two Phase 3 trials of about 1,640 patients each.

Both trials were stopped early, in March 2019, when an independent data monitoring committee said aducanumab didn’t appear to be working. Consequently, 37 percent of participants never completed the 78-week trials.

But that October, Biogen announced it found benefit in one trial after evaluating data from 318 participants who finished before the trials were stopped but after the cutoff point for results the monitoring committee assessed.

In that trial, Biogen said, the highest dose slowed cognitive decline by 22 percent, or about four months over 18 months. A lower dose in that trial and high and low doses in the other showed no statistically significant benefit over a placebo.

“One study was positive, and one identically performed study was negative,” said Dr. David Knopman, a clinical neurologist at the Mayo Clinic and a site principal investigator for one trial. “I don’t think it takes a Ph.D. in statistics to see that that’s inconclusive.”

Dewayne Nash, whose mother and brother died of Alzheimer’s, said that for his personal situation, he favored approval because he might decline before other treatments became available. But scientifically, “they really ought to do the studies” first, he said, adding that otherwise, “you’re giving people a drug that may help, but it may not.”Daniel Dreifuss for The New York Times

Dr. Alexander added that Biogen’s interpretation of data using after-the-fact analyses was “like the Texas sharpshooter fallacy — the idea that the sharpshooter shoots up a barn and then goes and draws a bull’s-eye around the cluster of holes that he likes.”

By contrast, Dr. Stephen Salloway, who has received research and consulting fees from Biogen but wasn’t paid for being an aducanumab trial site principal investigator, called himself a “passionate” supporter of approval. He considers the evidence sufficient because Alzheimer’s is so disabling.

“I understand people’s concerns — the data set has issues, of course,” said Dr. Salloway, director of neurology and the Memory and Aging Program at Butler Hospital in Providence, R.I. “F.D.A. is in a tough spot, obviously.”

But he favors giving patients the option. Of his 17 participants in both the safety trial and Phase 3, he said, 10 had remained relatively cognitively stable for several years, while seven had declined at typical rates.

“It didn’t work for everybody,” he said, but “it just seemed like there were more people that were steady for longer than I’m used to.”

One challenge with assessing impact is that many early-stage patients decline slowly anyway, Dr. Schneider said.

Advocates and many patients say delaying deterioration even slightly is meaningful. But some experts say the single trial’s slowing of 0.39 on an 18-point scale rating memory, problem-solving skills and function may be imperceptible to patients’ experience and doesn’t justify approving a drug that floundered in another trial and carries risk of harm.

“This product, even in the best of circumstances, would be not terribly effective at all, with significant safety risks,” Dr. Alexander said.

The potential harm involves brain swelling or bleeding experienced by about 40 percent of Phase 3 trial participants receiving the high dose. Most were either asymptomatic or had headaches, dizziness or nausea. But such effects prompted 6 percent of high-dose recipients to discontinue. No Phase 3 participants died from the effects, but one safety trial participant did.

Henry Magendantz, center, with his wife, Kathy Jellison, who believes his initial years on the drug helped slow his decline enough to allow him to help choose the assisted-living facility where he lives now. “It brought us some time,” she said. Kayana Szymczak for The New York Times

Some trial participants’ views reflect the situation’s complexity.

Dewayne Nash, 71, of Santa Barbara, Calif., learned after the trial that he had received 18 months of a placebo, during which his cognitive scores improved — partly, he believes, because he lowered his cholesterol. Dr. Nash, a retired family physician, then received seven months of aducanumab, scaling up to the high dose, hoping it would slow decline, but “I didn’t notice any difference.”

Dr. Nash, whose mother and brother died of Alzheimer’s, will resume aducanumab soon through Biogen’s study for previous participants. He said that for his situation, he would like it approved because he expects to decline before other therapies become available and is willing to risk “brain bleeding and stuff.”

But scientifically, “I don’t like it when they rush drugs,” he said.

“They really ought to do the studies that need to be done” before approval, he added. Otherwise, “you’re giving people a drug that may help, but it may not.”

Dr. Salloway said one trial patient whose dementia had remained mild considerably longer than he’d expected was Henry Magendantz, a retired obstetrician-gynecologist in Providence, R.I. Dr. Magendantz, 84, started the safety trial after his wife, Kathy Jellison, noticed him having trouble following steps to assemble furniture.

He received a year of placebo, then a year of lower-dose aducanumab, then two years of the high dose before the 2019 halt. During that time, Ms. Jellison said, he was “slipping a bit,” but she believes aducanumab slowed decline enough to allow him to participate in tasks like choosing an assisted-living facility, where he moved in October 2018.

“It brought us some time,” she said.

Debby Rosencrantz, a trial participant, hopes for Alzheimer’s treatments that work well enough to curb her dementia. “It just feels like there’s a blank in places where there shouldn’t be a blank in my brain,” she said.Kayana Szymczak for The New York Times

Another issue with evaluating treatments is that some assessment scales, including in the aducanumab trials, involve reports from relatives or caregivers, who might miss subtle symptom progression.

“It is squishy stuff,” said Susan Woskie, a professor emeritus in public health at the University of Massachusetts Lowell, whose wife, Debby Rosenkrantz, 68, participated in the trial. “This stuff is really difficult, I think, to compile into metrics that have any validity.”

Ms. Rosenkrantz, a former social worker in Cambridge, Mass., said that while receiving roughly eight months of low-dose aducanumab in the trial, “I was really optimistic that there was a drug, and so for me it was like, yes, it’s working.”

Since restarting infusions in Biogen’s study for previous participants last September, though, “I haven’t noticed any change,” she said.

She experiences short-term memory loss and cannot follow recipes. “It just feels like there’s a blank in places where there shouldn’t be a blank in my brain,” she said.

Dr. Woskie said the couple yearns for treatments but that if the F.D.A. told Biogen, “‘No, we don’t fast-track approve you; come back when you have more data,’ that wouldn’t surprise me, and it might make sense.”

Some doctors who consider aducanumab’s evidence weak, including Dr. Knopman, say that if it is approved, they would tell patients their reservations but would feel ethically compelled to offer it.

Still, Dr. Jason Karlawish, a co-director of the University of Pennsylvania’s Penn Memory Center and a site investigator on Biogen-sponsored studies, said, “Physicians like me, who would be prescribers, are saying, ‘I want an effective drug to prescribe to my patients — but this is not the drug.’”

Alzheimer’s Drug Poses a Dilemma for the F.D.A.

The Food and Drug Administration is on the verge of announcing one of its most contentious decisions in years: the fate of an Alzheimer’s drug that could be the first treatment approved after nearly two decades of failed efforts to find ways to curb the debilitating disease.

On Monday, the agency will rule on the drug, aducanumab, which aims to slow progression of memory and thinking problems early in the disease. If approved, it would be the first new Alzheimer’s medication since 2003 and the first treatment on the market that attacks the disease process rather than just easing symptoms.

It would become a blockbuster drug within several years, analysts predict, costing tens of thousands of dollars annually per patient and bringing a windfall to its manufacturer, Biogen.

Patient groups, desperate for treatments, are pushing for approval. But greenlighting the drug would fly in the face of objections from several prominent Alzheimer’s experts and the F.D.A.’s independent advisory committee.

In November, the committee voted overwhelmingly against recommending approval, saying data failed to demonstrate persuasively that aducanumab slowed cognitive decline. Three advisory committee members later wrote a point-by-point critique of the evidence. Other scientists, and an independent think tank, say aducanumab hadn’t shown convincing benefit to outweigh its safety risks.

“This should not be approved, because substantial evidence of effectiveness hasn’t been shown,” said Dr. Lon Schneider, director of the California Alzheimer’s Disease Center at the University of Southern California and one of many site investigators who helped conduct one of the aducanumab trials. “There’s very little potential that this will address the needs of patients.”

Beyond the status of this particular drug, some experts worry approval could lower standards for future drugs — an especially important question at a time when public trust in science is teetering.

“I simply don’t see a path for approval because of the absence of evidence that’s been shared to date that this product works, and I think it would set a remarkably dangerous precedent — not only for the field of Alzheimer’s research but also for the broader regulation of prescription drugs in our country,” said Dr. G. Caleb Alexander, an F.D.A. advisory committee member and an internist, epidemiologist and drug safety and effectiveness expert at the Johns Hopkins Bloomberg School of Public Health.

About six million people in the United States and roughly 30 million globally have Alzheimer’s, a number expected to double by 2050. Currently, five medications approved in the United States can delay cognitive decline for several months in various Alzheimer’s stages. About two million Americans have mild Alzheimer’s-related impairment, fitting criteria for aducanumab, a monthly intravenous infusion requiring regular imaging to detect potential brain swelling.

Biogen officials declined to comment for this article, but in earnings calls, medical meetings and F.D.A. presentations, they have said the evidence shows cognitive benefit. Several Alzheimer’s experts whose experience includes consulting for Biogen wrote recently that aducanumab “achieves the standard of meaningful efficacy with adequate safety.”

The Biogen headquarters in Cambridge, Mass.
The Biogen headquarters in Cambridge, Mass.Cody O’Loughlin for The New York Times

Debate centers on two never fully completed Phase 3 trials that contradicted each other. One suggested that a high dose could slightly slow cognitive decline; the other showed no benefit. Biogen says that given the need for Alzheimer’s medications, the single positive trial, plus results from a small safety trial and aducanumab’s ability to reduce a key protein, should justify approval.

The F.D.A. typically follows advisory committee recommendations and usually requires two convincing studies for approval, but it has made exceptions, especially for severe diseases that lack treatments.

Two other medications now in trials appear more promising than aducanumab, experts say, but it could be three or four years before data would indicate whether they merit approval. Many families say that’s too long to wait.

“There’s lots of issues with the data,” acknowledged Maria Carrillo, chief science officer for the Alzheimer’s Association, a patient advocacy group campaigning vigorously for approval. But she said her organization must “weigh the crushing reality of what people live with today” and support giving patients something to try instead of waiting several years for more conclusive positive results.

The F.D.A. itself seems divided. In advisory committee presentations, a clinical analyst cited “substantial evidence of effectiveness to support approval.” But an F.D.A. statistician wrote that another trial was needed because “there is no compelling, substantial evidence of treatment effect or disease slowing.”

And some experts, like Dr. Ronald Petersen, director of the Mayo Clinic’s Alzheimer’s Disease Research Center in Rochester, Minn., say they’re “on the fence.” He said he’d like to give patients a new option soon but “the data are iffy.”

Aducanumab, a monoclonal antibody, targets a protein, amyloid, that clumps into plaques in the brains of Alzheimer’s patients. Many amyloid-reducing drugs failed to slow symptoms in trials, a history that, some experts say, makes it especially important that aducanumab’s data be convincing. If effective, it would support a long-held, unproven theory that attacking amyloid can help if done early enough.

Excitement about aducanumab grew after a small early trial to evaluate safety showed amyloid reduction and hinted it might slow cognitive decline. The F.D.A., in a move some experts question, allowed Biogen to skip Phase 2 trials and conduct two Phase 3 trials of about 1,640 patients each.

Both trials were stopped early, in March 2019, when an independent data monitoring committee said aducanumab didn’t appear to be working. Consequently, 37 percent of participants never completed the 78-week trials.

But that October, Biogen announced it found benefit in one trial after evaluating data from 318 participants who finished before the trials were stopped but after the cutoff point for results the monitoring committee assessed.

In that trial, Biogen said, the highest dose slowed cognitive decline by 22 percent, or about four months over 18 months. A lower dose in that trial and high and low doses in the other showed no statistically significant benefit over a placebo.

“One study was positive, and one identically performed study was negative,” said Dr. David Knopman, a clinical neurologist at the Mayo Clinic and a site principal investigator for one trial. “I don’t think it takes a Ph.D. in statistics to see that that’s inconclusive.”

Dewayne Nash, whose mother and brother died of Alzheimer’s, said that for his personal situation, he favored approval because he might decline before other treatments became available. But scientifically, “they really ought to do the studies” first, he said, adding that otherwise, “you’re giving people a drug that may help, but it may not.”Daniel Dreifuss for The New York Times

Dr. Alexander added that Biogen’s interpretation of data using after-the-fact analyses was “like the Texas sharpshooter fallacy — the idea that the sharpshooter shoots up a barn and then goes and draws a bull’s-eye around the cluster of holes that he likes.”

By contrast, Dr. Stephen Salloway, who has received research and consulting fees from Biogen but wasn’t paid for being an aducanumab trial site principal investigator, called himself a “passionate” supporter of approval. He considers the evidence sufficient because Alzheimer’s is so disabling.

“I understand people’s concerns — the data set has issues, of course,” said Dr. Salloway, director of neurology and the Memory and Aging Program at Butler Hospital in Providence, R.I. “F.D.A. is in a tough spot, obviously.”

But he favors giving patients the option. Of his 17 participants in both the safety trial and Phase 3, he said, 10 had remained relatively cognitively stable for several years, while seven had declined at typical rates.

“It didn’t work for everybody,” he said, but “it just seemed like there were more people that were steady for longer than I’m used to.”

One challenge with assessing impact is that many early-stage patients decline slowly anyway, Dr. Schneider said.

Advocates and many patients say delaying deterioration even slightly is meaningful. But some experts say the single trial’s slowing of 0.39 on an 18-point scale rating memory, problem-solving skills and function may be imperceptible to patients’ experience and doesn’t justify approving a drug that floundered in another trial and carries risk of harm.

“This product, even in the best of circumstances, would be not terribly effective at all, with significant safety risks,” Dr. Alexander said.

The potential harm involves brain swelling or bleeding experienced by about 40 percent of Phase 3 trial participants receiving the high dose. Most were either asymptomatic or had headaches, dizziness or nausea. But such effects prompted 6 percent of high-dose recipients to discontinue. No Phase 3 participants died from the effects, but one safety trial participant did.

Henry Magendantz, center, with his wife, Kathy Jellison, who believes his initial years on the drug helped slow his decline enough to allow him to help choose the assisted-living facility where he lives now. “It brought us some time,” she said. Kayana Szymczak for The New York Times

Some trial participants’ views reflect the situation’s complexity.

Dewayne Nash, 71, of Santa Barbara, Calif., learned after the trial that he had received 18 months of a placebo, during which his cognitive scores improved — partly, he believes, because he lowered his cholesterol. Dr. Nash, a retired family physician, then received seven months of aducanumab, scaling up to the high dose, hoping it would slow decline, but “I didn’t notice any difference.”

Dr. Nash, whose mother and brother died of Alzheimer’s, will resume aducanumab soon through Biogen’s study for previous participants. He said that for his situation, he would like it approved because he expects to decline before other therapies become available and is willing to risk “brain bleeding and stuff.”

But scientifically, “I don’t like it when they rush drugs,” he said.

“They really ought to do the studies that need to be done” before approval, he added. Otherwise, “you’re giving people a drug that may help, but it may not.”

Dr. Salloway said one trial patient whose dementia had remained mild considerably longer than he’d expected was Henry Magendantz, a retired obstetrician-gynecologist in Providence, R.I. Dr. Magendantz, 84, started the safety trial after his wife, Kathy Jellison, noticed him having trouble following steps to assemble furniture.

He received a year of placebo, then a year of lower-dose aducanumab, then two years of the high dose before the 2019 halt. During that time, Ms. Jellison said, he was “slipping a bit,” but she believes aducanumab slowed decline enough to allow him to participate in tasks like choosing an assisted-living facility, where he moved in October 2018.

“It brought us some time,” she said.

Debby Rosencrantz, a trial participant, hopes for Alzheimer’s treatments that work well enough to curb her dementia. “It just feels like there’s a blank in places where there shouldn’t be a blank in my brain,” she said.Kayana Szymczak for The New York Times

Another issue with evaluating treatments is that some assessment scales, including in the aducanumab trials, involve reports from relatives or caregivers, who might miss subtle symptom progression.

“It is squishy stuff,” said Susan Woskie, a professor emeritus in public health at the University of Massachusetts Lowell, whose wife, Debby Rosenkrantz, 68, participated in the trial. “This stuff is really difficult, I think, to compile into metrics that have any validity.”

Ms. Rosenkrantz, a former social worker in Cambridge, Mass., said that while receiving roughly eight months of low-dose aducanumab in the trial, “I was really optimistic that there was a drug, and so for me it was like, yes, it’s working.”

Since restarting infusions in Biogen’s study for previous participants last September, though, “I haven’t noticed any change,” she said.

She experiences short-term memory loss and cannot follow recipes. “It just feels like there’s a blank in places where there shouldn’t be a blank in my brain,” she said.

Dr. Woskie said the couple yearns for treatments but that if the F.D.A. told Biogen, “‘No, we don’t fast-track approve you; come back when you have more data,’ that wouldn’t surprise me, and it might make sense.”

Some doctors who consider aducanumab’s evidence weak, including Dr. Knopman, say that if it is approved, they would tell patients their reservations but would feel ethically compelled to offer it.

Still, Dr. Jason Karlawish, a co-director of the University of Pennsylvania’s Penn Memory Center and a site investigator on Biogen-sponsored studies, said, “Physicians like me, who would be prescribers, are saying, ‘I want an effective drug to prescribe to my patients — but this is not the drug.’”

F.D.A. Approves New Drug to Treat Vaginal Yeast Infections

Regulators OK’d a new antifungal treatment, but critics say it is unneeded and costs too much.

The Food and Drug Administration on Tuesday approved a new drug to treat a vaginal yeast infection that is especially common in women who are pregnant, using birth control pills or taking antibiotics.

The drug, Brexafemme (ibrexafungerp) made by SCYNEXIS, is a one-day oral treatment and the first of a new class of triterpenoid antifungal drugs. The company said the new drug kills candida — the yeast that can cause an infection.

The standard oral medication, Diflucan (fluconazole), inhibits the growth of yeast but does not kill it.

But the treatment most likely wouldn’t be prescribed widely at first for common vaginal yeast infections. Dr. David Angulo, the company’s chief medical officer, estimated that the list price of the drug would range from $350 to $450 for the four-tablet treatment. By comparison, GoodRx lists the average retail price of fluconazole as $29.81.

He said Brexafemme was approved as a first-line treatment, but could also be prescribed for patients whose infections don’t clear up easily.

“There has been nothing new that can be provided to patients who can’t tolerate it, don’t respond well or develop resistance,” Dr. Angulo said.

Dr. Sumathi Nambiar, director of the F.D.A.’s division of anti-infectives said: “This approval for a new antifungal drug provides an additional treatment option for patients with vulvovaginal candidiasis, or vaginal or vulvar yeast infections, and represents another step forward in the F.D.A.’s overall efforts to ensure safe and effective antifungal drugs are available to patients.”

Dr. Denise Jamieson, chair of gynecology and obstetrics at Emory University School of Medicine, said she wasn’t sure the new drug was needed.

“I don’t see a tremendous amount of resistance,” she said. “I can’t really comment on whether this is going to be a large addition or not. It’s always helpful to have another option, and then you have to consider things like cost and tolerability.”

According to Dr. Angulo, one clinical trial used to support the application showed 50 percent efficacy — meaning complete resolution of all signs and symptoms — at 10 days after treatment and 60 percent 25 days after treatment. The other trial showed 64 percent efficacy at day 10 and 73 percent at day 25.

Dr. Michael Carome, director of Public Citizen’s Health Research Group, was not impressed by the F.D.A.’s approval of Brexafemme.

“This drug is not necessary and few women should need it,” Dr. Carome said. “Fluconazole is available at very low cost and in general is very effective. The cost of this is just outrageous.”

The F.D.A. is requiring SCYNEXIS to conduct several post-market studies, including one to assess the risks to pregnant women, the developing fetus and newborns; and another to study how much of the product goes into the breast milk of lactating women.

The drug will go on sale later this year.

‘Delayed Prescribing’ May Help Cut Down on Antibiotic Use

Most respiratory illnesses don’t require antibiotics, which can have harmful side effects.

Should you take antibiotics for a simple respiratory infection?

The Centers for Disease Control and Prevention recommends that health care personnel prescribe antibiotics sparingly, for many reasons. First, the overuse of the drugs leads to the development of resistant strains of bacteria, a growing problem that is reducing the effectiveness of all antibiotics. The drugs can also have serious side effects, ranging from mild rashes or diarrhea to less common and severe allergic reactions.

Because antibiotics can destroy normally helpful bacteria in the gut, their use can lead to life-threatening intestinal infections with Clostridioides difficile, or C. diff. The use of antibiotics in infancy and childhood has been linked to the development of allergic and autoimmune diseases, probably because they disturb the body’s normal balance of microorganisms. According to one estimate, adverse reactions to antibiotics result in 143,000 emergency room visits annually.

For all these reasons, most doctors have been trying to limit antibiotic use. For doctors and their professional organizations, “antibiotic stewardship” has become the watchword.

In some cases, the C.D.C. recommends an approach called “delayed prescribing.” With this approach, the doctor gives a patient a prescription for antibiotics, with instructions to wait a few days to fill it, and see if they get better without medicine. There is good evidence that this procedure is safe and effective for otitis media, a common ear infection, and for the nasal congestion of sinusitis.

Now a new review of studies, published in BMJ, suggests that delayed prescribing may also be a safe and effective approach for treating most respiratory tract infections. For their analysis, researchers combined individual patient data on more than 55,000 people in nine randomized controlled trials and four observational studies.

On average, they found no difference in follow-up on a seven-point symptom severity scale between patients given immediate antibiotics for respiratory infections and those given delayed prescriptions.

Those who got delayed prescriptions had symptoms for an average 11.4 days, about the same as those given no antibiotics at all, compared with 10.9 days for those given the drugs immediately. Patients who got delayed prescriptions were less likely to visit the doctor again, and were more satisfied with their treatment than those given no prescription.

In children younger than 5, symptoms were slightly more severe during follow-up in those given a delayed prescription rather than immediate antibiotics.

“A lot of these symptoms clear up in a few days anyway,” said the lead author, Beth Stuart, an associate professor at the University of Southampton in England. “So on average, antibiotics don’t have a huge benefit.”

“But what about special cases where antibiotics can be useful? Is delayed prescribing safe for them too?” she said. “Yes. It’s safe and effective to send them off with a delayed prescription and instructions about what to look for.”

But Dr. Jeffrey A. Linder, a professor of medicine at Northwestern who was not involved in the research, urged caution, noting that the data the researchers used did not properly distinguish diagnoses. “The most likely interpretation of the finding that there is no difference in symptom duration between patients who received immediate antibiotics, delayed antibiotics and no antibiotics,” he said, “is that most of these patients did not need antibiotics in the first place.”

The authors took measures to statistically account for differences between the various illnesses, he continued, but the study “mixes up clinical conditions that should be treated with antibiotics — strep throat, otitis media — with those that should not be — colds, acute bronchitis, viral pharyngitis.”

Dr. Holly M. Frost, an assistant professor of pediatrics at Denver Health who was not involved in the study, added that in real-world practice, few doctors use delayed prescriptions, even in cases where it is already recommended, much less for respiratory infections. “Almost everyone with ear infections and sinusitis is getting antibiotics,” she said.

Moreover, delayed prescriptions may not help with reducing antibiotic use, she said, since most people just go directly to the pharmacy with their “delayed” prescription anyway. In one medical practice she surveyed, she found that 93 percent of delayed prescriptions were filled immediately.

Lecturing patients about antibiotic resistance, she said, is not the right approach either. Rather, the approach should be, “You’re not going to feel any better if you take antibiotics.” She is not against the practice of offering delayed prescriptions, but sees it as one option among several.

“We have to explore any strategies we have for reducing antibiotic prescribing,” she said.

New Drugs Could Help Treat Obesity. Could They End the Stigma, Too?

Obesity has stalked Marleen Greenleaf, 58, all of her life. Like most people with obesity, she tried diet after diet. But the weight always came back.

With that, she has suffered a lifetime of scorn and stigma. Jeering comments from strangers when she walked down the street. Family members who told her, when she trained for a half-marathon, “I don’t think it’s good for you.”

Then, in 2018, Ms. Greenleaf, an administrator at a charter school in Washington, D.C., participated in a clinical trial for semaglutide, which is a new type of obesity drug, known as incretins.

Over the course of the 68-week study, Ms. Greenleaf slowly lost 40 pounds.

Until then, she had always believed that she could control her weight if she really tried.

“I thought I just needed more motivation,” she said. But when she took semaglutide, she said that “immediately, the urge to eat just dissipated.”

Incretins appear to elicit significant weight loss in most patients, enough to make a real medical and aesthetic difference. But experts hope that the drugs also do something else: change how society feels about people with obesity, and how people with obesity feel about themselves.

If these new drugs allow obesity to be treated like a chronic disease — with medications that must be taken for a lifetime — the thought is that doctors, patients and the public might understand that obesity is truly a medical condition.

“We all believe this drug will change the way we see obesity being treated,” said Dr. Caroline Apovian, an obesity specialist at Brigham and Women’s Hospital. (Dr. Apovian, like most leading obesity researchers, consults for several drug companies. She is on the advisory board of Novo Nordisk, the maker of semaglutide, and is paid for attending advisory board meetings.)

Decades of studies have repeatedly showed that there are powerful biological controls over individual body weights. Identical twins reared apart had nearly identical body weights. Adopted children ended up with body mass indexes like those of their biological parents, not those of their adoptive parents. Metabolism slows as people lose weight, forcing them to regain it.

And yet, obesity “is like having a mark on your forehead,” said Dr. Scott Kahan, chair of the clinical committee for The Obesity Society, a scientific membership organization.

People with obesity are more likely to be passed over for jobs, be paid less than others with the same abilities and training, and be treated poorly by doctors, who spend less time with them and offer fewer preventive services.

But people with obesity haven’t had many places to turn for help. The current obesity drugs lead to an average weight loss of only 5 percent to 10 percent. And because some of these drugs are approved only for limited time frames, the lost pounds almost always come back when the intervention ceases.

According to these studies, incretins seem to be different. Unlike other weight-loss drugs, they are naturally occurring hormones that affect systems central to obesity. The drugs slow stomach emptying, regulate insulin and decrease appetite, with mostly mild to moderate short-term gastrointestinal side effects.

The drugs will not banish obesity or make people truly thin. But people who take them can look and feel very different. For some, the medications lead to weight loss approaching that of bariatric surgery.

If incretins pass the approval process, they might help convince the most important constituency of all — doctors — that obesity is a chronic disease and that it can be treated, said Dr. Robert F. Kushner, an obesity researcher and clinician at Northwestern University. One reason many doctors don’t help patients with obesity is that they don’t know how, Dr. Kushner said. Diets and exercise, the usual nostrums, almost always provide short-term weight loss, at best.

Dr. Robert F. Kushner, an obesity researcher and clinician at Northwestern University. “I tell them this is a chronic ongoing medical problem, just like diabetes,” he said.
Dr. Robert F. Kushner, an obesity researcher and clinician at Northwestern University. “I tell them this is a chronic ongoing medical problem, just like diabetes,” he said.Taylor Glascock for The New York Times

The incretin taken by Ms. Greenleaf, semaglutide, made by Novo Nordisk, is before the Food and Drug Administration, with a decision expected in June. On average it elicited a 15 percent weight loss, but a third of those who took it lost 20 percent or more of their body weight in the study, similar to the amount lost with lap-band bariatric surgery.

Eli Lilly has a similar drug, tirzepatide, which combines two incretins. The company is testing it against semaglutide and hopes that it will be even more powerful.

Dr. Louis J. Aronne, an obesity specialist at Cornell Medical School, said that the combination of semaglutide and another experimental Novo Nordisk drug, cagrilintide, could produce as much as a 25 percent weight loss in a year, an amount like that achieved with sleeve gastrectomy, a popular form of bariatric surgery.

Although more than a half-dozen new hormonal drugs are being tested, Dr. Kushner said, only with long-term use can researchers learn if the new drugs control the many medical consequences of obesity, like diabetes and high blood pressure.

There is also the larger riddle of biological destiny: Are the body’s multiple and redundant systems to maintain body weight so powerful that they will exert control in the end, diminishing the effectiveness of the drugs?

Like other obesity specialists, Dr. Rudolph L. Leibel, a researcher at Columbia University who conducted many of the pivotal studies showing obesity is a disease, deplores society’s bias against his patients. But he has his doubts that perceptions will change with new treatments.

“My guess is that bias will persist and might even be exacerbated by the availability of ‘an easy way out,’” he said.

Dr. Kushner is more hopeful and points to the example of statins, which lower cholesterol and became available in the late 1980s. Until then, doctors could only suggest that patients with high cholesterol cut back on eggs and red meat.

Doctors “embraced statins,” Dr. Kushner said, because they could at last treat this condition. More powerful incretins, he added, could have the same effect on the medical profession.

He is unsure, though, whether patients will accept the disease label. They’ve been conditioned, he said, to believe that their weight is their own fault; all they have to do is eat healthier and exercise more.

When talking with patients, he doesn’t spend 20 minutes trying to convince them that they have a disease. In fact, he deliberately avoids using the word “disease” and instead says “condition” or “problem.”

“I tell them this is a chronic ongoing medical problem, just like diabetes,” he said.

Members of the general public pose a different challenge, Dr. Kushner said. With them, he said, “we may need to use a term like ‘disease.’”

He likens the situation to that of alcoholism or drug addiction, which was once thought to be indicative of a weak will or a moral failing. Researchers have successfully changed the conversation; many people now know that those who abuse alcohol or drugs have a disease and need treatment.

As for Ms. Greenleaf, she wants to take semaglutide again. The pounds crept back when the trial ended.

Obesity, she now realizes, “is not your fault.”

FDA Authorizes Pfizer-BioNTech Vaccine for Children 12 to 15

The shots may allow millions of youngsters to get back to school, camps, sleepovers and hangouts with friends.

The Food and Drug Administration on Monday authorized use of the Pfizer-BioNTech Covid-19 vaccine for 12- to 15-year-olds in the United States, a crucial step in the nation’s steady recovery from the pandemic and a boon to millions of American families eager for a return to normalcy.

The authorization caps weeks of anticipation among parents, who have been grappling with how to conduct their lives when only the adults in a household are immunized. It removes an obstacle to school reopenings by reducing the threat of transmission in classrooms, and affords more of the nearly 17 million children in this age group opportunities to attend summer camps, sleepovers and Little League games.

“This is great news,” said Dr. Kristin Oliver, a pediatrician and vaccine expert at Mount Sinai Hospital in New York. “It feels like we’ve been waiting a long time to start protecting children in this age group.” The Pfizer-BioNTech vaccine is already available to anyone over 16.

The F.D.A.’s go-ahead is not the final hurdle. An advisory committee of the Centers for Disease Control and Prevention is expected to meet shortly to review the data and make recommendations for the vaccine’s use in 12- to 15-year-olds.

If the committee endorses the vaccine for that age group, as expected, immunizations in theory can begin immediately. Clinical trials have shown that these children may safely receive the dose already available for adults.

President Biden has said that about 20,000 pharmacies are ready to administer the vaccine to adolescents, and health officials in some states are already drawing up immunization campaigns targeted to youngsters.

In a clinical trial, Pfizer and BioNTech enrolled 2,260 participants ages 12 and 15 and gave them either two doses of the vaccine or a placebo three weeks apart. The researchers recorded 18 cases of symptomatic coronavirus infection in the placebo group, and none among the children who received the vaccine, indicating that it was highly effective at preventing symptomatic illness.

The vaccine also appeared to be safe for these children, with side effects comparable to those seen in trial participants who are 16 to 25 years old. Fevers were slightly more common among inoculated 12- to 15-year-olds; about 20 percent of them had fevers, compared with 17 percent in the older age group.

The trend toward more fevers at younger ages was consistent with observations in an earlier trial, said Dr. Bill Gruber, a senior vice president at Pfizer and a pediatrician.

The trial results were a “trifecta” of good news, Dr. Gruber added: “We have safety, we got the immune response we wanted — it was actually better than what we saw in the 16- to 25-year-old population — and we had outright demonstration of efficacy.”

The company is still gathering information on potential asymptomatic infections by continuing to test the trial participants for the coronavirus every two weeks and checking them for antibodies produced in response to a natural infection, according to Dr. Gruber.

The authorization arrives at a opportune time. Roughly one-third of eighth graders, usually 13 and 14 years old, are still learning fully remotely, and widespread vaccination may help speed a return to classrooms.

Coronavirus outbreaks have been a concern particularly for students participating in team sports, and immunizations should ease the concerns of many parents whose children have been unable to participate in football, basketball and other team sports involving close contact.

In summer, families often catch up the vaccinations required for children to return to schools in the fall, and so pediatricians and family doctors may be best positioned to immunize young teenagers as they come in for annual physical examinations.

The Pfizer-BioNTech vaccine can be stored for only five days in standard refrigerators, but the companies are planning to ship smaller packs for doctors’ offices. It is also developing a formulation that can be refrigerated for up to 10 weeks.

The push to immunize children may run into the same problems with hesitancy that have plagued attempts to inoculate adults. In one recent poll, 30 percent of parents said they would have their children vaccinated right away, while 26 percent said they planned to wait to see how the vaccine was working.

Most of the other parents said they would definitely not have their children vaccinated, or would do so only if schools required it. All 50 states require certain vaccines for children who attend school, but those mandates apply only to vaccines that have been fully approved by the F.D.A. The Pfizer-BioNTech vaccine has been authorized only for emergency use.

The companies have applied to the F.D.A. for full approval, but that process is expected to take several months. Even after approval, students may still opt out by citing medical reasons or religious beliefs.

Still, scientists agreed that the vaccine appeared to meet all expectations regarding safety and efficacy. Dr. Megan Ranney, an emergency room physician and professor at Brown University in Providence, R.I., said she had “zero safety concerns” about the Pfizer-BioNTech vaccine, noting that hundreds of millions of people worldwide had received it.

Her 12-year-old daughter is eager to be vaccinated, and her 9-year-old son will be immunized as soon as he is eligible, she said. Dr. Ranney has not allowed her children to sleep at friends’ houses since the pandemic began. The vaccine should allow them to safely resume social activities, she said.

“The risk of your child catching Covid and getting really sick is low, but it’s not zero,” she said. “And the risk of them getting sick or hospitalized or worse with Covid or with the post-Covid multi-inflammatory syndrome is higher than the risk of something bad from this vaccine.”

Vaccinating children shields others in the community from the virus, she noted, including people who are not protected by the vaccine, such as organ transplant recipients, cancer patients and those with impaired immune responses.

“It also protects all of us from the virus continuing to spread and mutating further,” Dr. Ranney said. “That’s the thing that I’m most scared of right now.”

Vaccinating children is crucial to building up population levels of immunity and curtailing the spread of the coronavirus. Though children spread the virus less efficiently than adults do, they make up about 23 percent of the population.

Experts have said that the country is unlikely to reach the “herd immunity” threshold — the point at which virus transmission essentially stalls — but vaccinating children will be important for getting as close as possible.

Ty Dropic, 14, one of the trial participants, urged others his age to be vaccinated so they could build up widespread immunity and protect themselves. He had no side effects, leading him to suspect that he got the placebo. If that turns out to be the case, he plans to be immunized as soon as possible.

“I know it can be kind of scary, but it’s really not as bad as it seems,” he said. “If you do get Covid, it’ll be a lot worse than getting stuck with a needle for, like, two seconds.”

Ty’s three siblings, ages 8, 10 and 16, are also enrolled in vaccine trials for their age groups. Their mother, Dr. Amanda Dropic, a pediatrician in northern Kentucky, said that in her practice, most parents were eager to have their children vaccinated so they could regain some semblance of normalcy.

“The anxiety and depression that we’re seeing with kids, the social delays, has been tremendous,” she said.

Dr. Dropic said her children understood the risks and were willing to volunteer because they saw it as a civic duty. Every medicine available today came to be because “somebody was willing to go first,” she added.

Pfizer and BioNTech began testing the vaccine in children ages 5 to 11 in March, and last month extended the trial to even younger children, ages 2 to 5. The companies next plan to test children who are 6 months to 2 years old.

Assuming trial results are encouraging, the companies expect to apply to the F.D.A. in September for emergency authorization to administer the vaccine to children ages 2 to 11.

Results from trials of Moderna’s vaccine in 12- to 17-year-olds are expected in the next few weeks. Findings from another trial of the company’s vaccine in children 6 months to 12 years old should be available in the second half of this year.

AstraZeneca is testing its vaccine in children 6 months and older. Johnson & Johnson plans to wait for results from trials in participants older than 12 before testing its vaccine in younger children.

Jan Hoffman contributed reporting.

F.D.A. Authorizes Pfizer-BioNTech Vaccine for Children 12 to 15

The shots may allow millions of youngsters to get back to school, camps, sleepovers and hangouts with friends.

The Food and Drug Administration on Monday authorized use of the Pfizer-BioNTech Covid-19 vaccine for 12- to 15-year-olds in the United States, a crucial step in the nation’s steady recovery from the pandemic and a boon to millions of American families eager for a return to normalcy.

The authorization caps weeks of anticipation among parents, who have been grappling with how to conduct their lives when only the adults in a household are immunized. It removes an obstacle to school reopenings by reducing the threat of transmission in classrooms, and affords the nearly 17 million children in this age group the opportunity to attend summer camps, sleepovers and Little League games.

“This is great news,” said Dr. Kristin Oliver, a pediatrician and vaccine expert at Mount Sinai Hospital in New York. “It feels like we’ve been waiting a long time to start protecting children in this age group.” The Pfizer-BioNTech vaccine is already available to anyone over 16.

The F.D.A.’s go-ahead is not the final hurdle. An advisory committee of the Centers for Disease Control and Prevention is expected to meet shortly to review the data and make recommendations for the vaccine’s use in 12- to 15-year-olds.

If the committee endorses the vaccine for that age group, as expected, immunizations in theory can begin immediately. Clinical trials have shown that these children may safely receive the dose already available for adults.

President Biden has said that about 20,000 pharmacies are ready to administer the vaccine to adolescents, and health officials in some states are already drawing up immunization campaigns targeted to youngsters.

In a clinical trial, Pfizer and BioNTech enrolled 2,260 participants ages 12 and 15 and gave them either two doses of the vaccine or a placebo three weeks apart. The researchers recorded 18 cases of symptomatic coronavirus infection in the placebo group, and none among the children who received the vaccine, indicating that it was highly effective at preventing symptomatic illness.

The vaccine also appeared to be safe for these children, with side effects comparable to those seen in trial participants who are 16 to 25 years old. Fevers were slightly more common among inoculated 12- to 15-year-olds; about 20 percent of them had fevers, compared with 17 percent in the older age group.

The trend toward more fevers at younger ages was consistent with observations in an earlier trial, said Dr. Bill Gruber, a senior vice president at Pfizer and a pediatrician.

The trial results were a “trifecta” of good news, Dr. Gruber added: “We have safety, we got the immune response we wanted — it was actually better than what we saw in the 16- to 25-year-old population — and we had outright demonstration of efficacy.”

The company is still gathering information on potential asymptomatic infections by continuing to test the trial participants for the coronavirus every two weeks and checking them for antibodies produced in response to a natural infection, according to Dr. Gruber.

The authorization arrives at a opportune time. Roughly one-third of eighth graders, usually 13 and 14 years old, are still learning fully remotely, and widespread vaccination may help speed a return to classrooms.

Coronavirus outbreaks have been a concern particularly for students participating in team sports, and immunizations should ease the concerns of many parents whose children have been unable to participate in football, basketball and other team sports involving close contact.

In summer, families often catch up the vaccinations required for children to return to schools in the fall, and so pediatricians and family doctors may be best positioned to immunize young teenagers as they come in for annual physical examinations.

The Pfizer-BioNTech vaccine can be stored for only five days in standard refrigerators, but the companies are planning to ship smaller packs for doctors’ offices. It is also developing a formulation that can be refrigerated for up to 10 weeks.

The push to immunize children may run into the same problems with hesitancy that have plagued attempts to inoculate adults. In one recent poll, 30 percent of parents said they would have their children vaccinated right away, while 26 percent said they planned to wait to see how the vaccine was working.

Most of the other parents said they would definitely not have their children vaccinated, or would do so only if schools required it. All 50 states require certain vaccines for children who attend school, but those mandates apply only to vaccines that have been fully approved by the F.D.A. The Pfizer-BioNTech vaccine has been authorized only for emergency use.

The companies have applied to the F.D.A. for full approval, but that process is expected to take several months. Even after approval, students may still opt out by citing medical reasons or religious beliefs.

Still, scientists agreed that the vaccine appeared to meet all expectations regarding safety and efficacy. Dr. Megan Ranney, an emergency room physician at Rhode Island Hospital in Providence, said she had “zero safety concerns” about the Pfizer-BioNTech vaccine, noting that hundreds of millions of people worldwide had received it.

Her 12-year-old daughter is eager to be vaccinated, and her 9-year-old son will be immunized as soon as he is eligible, she said. Dr. Ranney has not allowed her children to sleep at friends’ houses since the pandemic began. The vaccine should allow them to safely resume social activities, she said.

“The risk of your child catching Covid and getting really sick is low, but it’s not zero,” she said. “And the risk of them getting sick or hospitalized or worse with Covid or with the post-Covid multi-inflammatory syndrome is higher than the risk of something bad from this vaccine.”

Vaccinating children shields others in the community from the virus, she noted, including people who are not protected by the vaccine, such as organ transplant recipients, cancer patients and those with impaired immune responses.

“It also protects all of us from the virus continuing to spread and mutating further,” Dr. Ranney said. “That’s the thing that I’m most scared of right now.”

Vaccinating children is crucial to building up population levels of immunity and curtailing the spread of the coronavirus. Though children spread the virus less efficiently than adults do, they make up about 23 percent of the population.

Experts have said that the country is unlikely to reach the “herd immunity” threshold — the point at which virus transmission essentially stalls — but vaccinating children will be important for getting as close as possible.

Ty Dropic, 14, one of the trial participants, urged others his age to be vaccinated so they could build up widespread immunity and protect themselves. He had no side effects, leading him to suspect that he got the placebo. If that turns out to be the case, he plans to be immunized as soon as possible.

“I know it can be kind of scary, but it’s really not as bad as it seems,” he said. “If you do get Covid, it’ll be a lot worse than getting stuck with a needle for, like, two seconds.”

Ty’s three siblings, ages 8, 10 and 16, are also enrolled in vaccine trials for their age groups. Their mother, Dr. Amanda Dropic, a pediatrician in northern Kentucky, said that in her practice, most parents were eager to have their children vaccinated so they could regain some semblance of normalcy.

“The anxiety and depression that we’re seeing with kids, the social delays, has been tremendous,” she said.

Dr. Dropic said her children understood the risks and were willing to volunteer because they saw it as a civic duty. Every medicine available today is because “somebody was willing to go first,” she added.

Pfizer and BioNTech began testing the vaccine in children ages 5 to 11 in March, and last month extended the trial to even younger children, ages 2 to 5. The companies next plan to test children who are 6 months to 2 years old.

Assuming trial results are encouraging, the companies expect to apply to the F.D.A. in September for emergency authorization to administer the vaccine to children ages 2 to 11.

Results from trials of Moderna’s vaccine in 12- to 17-year-olds are expected in the next few weeks. Findings from another trial of the company’s vaccine in children 6 months to 12 years old should be available in the second half of this year.

AstraZeneca is testing its vaccine in children 6 months and older. Johnson & Johnson plans to wait for results from trials in participants older than 12 before testing its vaccine in younger children.

Jan Hoffman contributed reporting.