Tag: drugs

With social media fueling the huge demand for drugs like Ozempic, Rybelsus, Wegovy, and Mounjaro, which are helping people to lose more weight than any previous weight loss medications, it’s no surprise that manufacturers have had trouble keeping up. And the recent approval of Eli Lilly’s Zepbound, which is the same drug, Mounjaro, approved already for diabetes, but renamed specifically for weight management, will only add to that demand. Novo Nordisk, which makes Ozempic, Wegovy, and Rybelsus, for example, has intentionally held back the release of new starter doses of Wegovy to ensure that those who have already started on the weight loss drug can continue getting their injections despite the current limited availability and manufacturing schedules.

But as with many situations in which supply far exceeds demand, questionable versions of these drugs are making their way into desperate patients’ hands, and doctors are concerned about what exactly these versions contain. Some online sellers are exploiting the opportunity to cash in, selling knockoffs of Wegovy, whose active ingredient is semaglutide, that may not even contain semaglutide. Novo Nordisk, which still holds the patent on Ozempic and Wegovy, has also stepped in to address illicit versions of these drugs, suing medical spas, weight loss clinics, and compounding pharmacies in the U.S. that the company alleges are selling unapproved versions of its brand-name drugs, made with versions of semaglutide that the FDA does not sanction. (TIME reached out to the compounding pharmacies named in the suits, in Florida and Tennessee, and did not receive responses.)

Compounding pharmacies occupy a gray area in the current market for weight loss drugs. These pharmacies are licensed and regulated by state boards of pharmacy, and are legally allowed to make tailored versions of drugs that are customized to fit individual patients’ needs. For example, they can remove or substitute ingredients that might cause an allergic reaction. Or they might create a more palatable tasting medicine, reformulate a drug from a pill or tablet to a liquid for those who have difficulty swallowing, or mix up different doses of a drug that aren’t available with the branded version.

These drugs can be prescribed, made, and dispensed under Section 503A of the Federal Food, Drug, and Cosmetic Act, which permits compounding pharmacies to come up with their own recipes for copies of brand name drugs, much like the original apothecary pharmacists of centuries ago. But because they are producing customized versions of approved drugs, compounding pharmacists do not have to notify or receive authorization from the Food and Drug Administration (FDA) to make them, and the FDA does not review them for safety and efficacy. Compounding pharmacies are also allowed to produce more-or-less exact versions of branded drugs that are on the FDA’s drug shortage list, in order to address supply constraints. Semaglutide currently falls into that category, and Novo Nordisk says supplies of both semaglutide and the auto-injector pen device can’t keep up with the surge in demand for its drugs. While tirzepatide, the main ingredient in Mounjaro and Zepbound, is also listed in short supply for people with diabetes, Lilly executives say it’s now available, for people who need it for either diabetes or weight management, although it may take the FDA some time to verify how that supply compares to demand and remove it from the list.

Read more: Should We End Obesity?

While the practice of compounding is legal, some health experts, including the FDA, have raised concerns about how some compounding pharmacists are producing semaglutide. The branded—and FDA-approved—versions of Ozempic, Wegovy, and Rybelsus contain semaglutide made from a specific form of the compound, known as its base. But some compounding pharmacies have used the salt forms of semaglutide to meet the surge in demand, prompting the FDA to issue a warning on May 31. In its statement, the FDA said that compounders should only be using the base form of semaglutide, and that “the salt forms are different active ingredients than is used in the approved drugs.” In addition, the FDA said it is “not aware of any basis for compounding using the salt forms that would meet the [Food, Drug and Cosmetic Act] requirements for active ingredients that can be compounded.” Following the FDA’s lead, several state pharmacy boards of pharmacy, including those in Mississippi, Louisiana, and North Carolina have issued similar warnings to their pharmacies.

Some compounding pharmacists are pushing back, arguing that if the final product made with semaglutide salts does meet the FDA’s criteria for potency, sterility, and lack of endotoxins, it should be considered a legitimately compounded product. They point out that if semaglutide salts are dissolved, they form semaglutide base, so the end product is the same. They are also finding enough supply of both semaglutide base and salts from FDA-sanctioned facilities for compounding, which in their view means that the constrained supply of the branded drug may be more related to the availability of the sterile syringe in which the drug is given. They maintain that using the salt forms are a valid way to compound semaglutide. “I do think there is nuance there,” says one compounding pharmacist who asked not to be named. “The package insert [for the name-brand drug], which is where we start, says [it includes] semaglutide and two normal buffers that are commonly used in injectable medications.” In theory, that means a semaglutide salt-based version would match the FDA-approved drug.

The explosive demand for semaglutide-based weight loss drugs, fueled by their ability to help people shed 15% or more of body weight—more than any previously approved medication—has raised the visibility of compounding pharmacies and how they operate. It’s also placed an additional burden on patients of vetting the facilities that they turn to in order to fill prescriptions. 

How does compounding work without a recipe for the drug

To make something like Wegovy, a compounding pharmacist begins by looking at the ingredient list on the drug’s package insert. All ingredients must come from FDA-registered manufacturers, which ensures their quality. From there, things become a little less rote, as the pharmacists come up with their own formula for reaching the right concentration of active ingredient to achieve the drug’s potency. ”It’s a lot like cooking,” says the compounding pharmacist who asked to not be identified. “You look at recipes but often don’t have every ingredient in the recipe, so you make modifications based on experience. It’s hard for people not in the industry to understand—it’s the old school way of making medicine where everything is customized. It’s not black and white.”

For semaglutide, the formula is relatively simple: “It’s semaglutide, the active ingredient, dissolved in solution,” says Scott Brunner, CEO of the Alliance for Pharmacy Compounding. “It’s not hard for a compounding pharmacist to make.”

In addition to potency, since semaglutide is an injected drug, the pharmacist must also ensure that it’s sterile and does not contain any contaminants such as bacteria-produced toxins. Once they come up with a product, compounding pharmacists then send their formulations to an independent lab—which generally follow similar standards for testing—to verify the potency, sterility, and safety of the drug. 

Most compounded versions are legitimate copies of the branded drugs. “Compounding pharmacists are not a bunch of people making sketchy substances in their garage,” says Brunner. 

But for now, much of the burden of ensuring that these compounded drugs are legitimate still rests on patients, with a system that relies too heavily on caveat emptor. Patients can ask compounding pharmacies for results of the testing from independent labs verifying the safety, sterility, and quality of the product they are purchasing. But compounding pharmacies don’t have to proactively report testing results of each product to their state boards; they are only required to keep logs of the sources of their raw ingredients and the process they used to make the drug.

States have varying levels of oversight over these pharmacies, so some may conduct more rigorous and frequent inspections of these records, while others perform them more sporadically. In addition, “inspections and investigations are typically done after the fact, after someone reports an adverse reaction or files a complaint,” says David Margraf, pharmaceutical research scientist at the Center for Infectious Disease Research and Policy at the University of Minnesota. “And state boards of pharmacy are typically not well-funded so they don’t have time to investigate everything.” Several pharmacy boards, including Nevada’s have launched investigations into products made by compounding pharmacies in their state. The Nevada board of pharmacy did not immediately respond to requests about the status of the investigation.

When Jess Holmes, a digital marketing entrepreneur living in Gilbert, Ariz., went to her naturopath to discuss using semaglutide to help with liver issues and other health concerns that could be alleviated with weight loss, he suggested getting a compounded version of the drug. Because access to branded versions of the drug was limited, he felt submitting a claim through Holmes’ insurance would take too long. “I had no idea what a compounding pharmacy was, or how it worked,” she says. Her naturopath recommended a specific compounding pharmacy, Strive, that he had used regularly. Holmes educated herself a little more about compounding and did some research on the facility herself, and “didn’t see anything shady that raised a red flag.”

When she went to pick up her first set of injections a few days later, she asked the pharmacist about the controversy over how compounded semaglutide is made, and asked him to confirm that the drug she was getting was indeed semaglutide. “They reassured me that it was, and I can only go by what they say,” she says. “For me that was all I needed.” Holmes has been injecting herself with compounded semaglutide for several months now, and only experienced side effects of nausea, diarrhea, and a headache the day after her first shot. Since then, she hasn’t had many adverse reactions to the drug, and it seems to be working; so far, she’s lost more than 23 pounds.

Compounding pharmacies are only one alternative source of branded semaglutide. Online retailers, many without proper licenses or any oversight at all, may be selling what they claim to be semaglutide, but are actually something else, says Al Carter, executive director of the National Association of Boards of Pharmacy. These sites often don’t even require a prescription—legitimate compounding pharmacies will require a prescription written specifically for compounded semaglutide. Carter says there are some other warning signs of illegitimate sites including promises of 24 hour delivery and enticingly lower prices. The FDA suggests patients consult BeSafeRx before purchasing medications from an online pharmacy, medical spa, wellness clinic, or other purported sellers. Patients can also find legitimate local compounding pharmacies through referrals from their prescriber, or by using resources such as the Alliance for Compounding Pharmacy.

Meanwhile, the demand for compounded forms of Wegovy and Ozempic has grown so much that it’s become exhausting, says the anonymous compounding pharmacist, noting that they dispense about 1,000 vials of semaglutide a week. “I honestly don’t know how doctors and patients find us. I understand that there is a lot of demand in the marketplace for patients with health problems like diabetes, and I want to help those people. But TikTok and Instagram ruined it for us. You can’t differentiate what the patients are using it for. We want to help the patients who need [the drug], but now it seems the majority of patients who are coming with prescriptions are moms who want to lose 10 pounds.”

The financial burden of high insulin costs that patients and insurers face is often blamed on the Food and Drug Administration’s (FDA) regulatory framework, but a new study suggests pharmaceutical companies have also been using patenting processes to unfairly maintain high costs. In the FDA’s master list of approved medications, devices, and other therapeutics, a document known as the Orange Book, patent ownership of each item governs which companies are allowed to manufacture and sell which therapies. The FDA deals with drug approval, but patents are granted by another agency entirely, the U.S. Patent and Trademark Office (USPTO).

Though there are rules governing which developments by pharmaceutical companies merit inclusion in the FDA’s Orange Book, experts have long said that the book remains full of improper patents that unfairly hamper market competition. Because patents in the Orange Book lock in a period of market exclusivity for the holder that’s stayed at least 30 months even in the face of legal challenges from smaller companies, filing additional patents on product lines can allow manufacturers to operate without competition—and thus sell at higher prices—for longer periods of time. While a patent remains in the Orange Book, the FDA cannot approve an equivalent generic. 

A Nov. 16 study highlights how the ease of manipulating the Orange Book has caused pricing issues for one group of therapeutics: insulin products. The gaming of the patent process is rife in the insulin marketplace, says William Feldman, an associate physician at Brigham and Women’s Hospital, instructor at Harvard Medical School, and a lead author of the new study, published in PLOS Medicine. And even in the wake of a March 2023 commitment from manufacturers to cap out-of-pocket insulin costs at $35 a month, “you still have a system where there’s not enough competition, and prices are still too high for these drugs that have been around for a long time,” Feldman says. 

Feldman and his colleagues analyzed all publicly available FDA and patent data on insulin products from 1986 to 2019. “We went through every single Orange Book from every single year, and picked out every single patent on every single insulin product,” says Feldman. In this time period, 56 brand-name insulin products were approved, many from some of the world’s largest pharma companies, including Eli Lilly and Novo Norodisk. They also looked at the patent history of other small-molecule drugs (a category to which insulin belonged until 2020, when it was more accurately recategorized as a biologic). While there was opportunistic patenting across the board, the median number of years of market protection for all of the small-molecule drugs was 14; insulin products, however, averaged 16 years.

“One thing we looked at is patents that were filed after FDA approval,” Feldman says. These delayed patents, which can be applied to either a drug or a delivery mechanism like an injector, are a sign of what experts call “patent thickets,” or groups of patents that overlap in complex ways that can make legal challenges more difficult. For drugs like insulin, which require delivery devices, these thickets are much easier to create, as nearly every element of a device can receive its own patent. Often, says Feldman, the patents that prevent potential competitors from offering insulin systems are “on parts of the pens that don’t mention insulin at all.”

In a civil case decided against Sanofi—one major manufacturer of insulin products—in 2021, the First Circuit court ruled that patents disconnected from the active ingredient of a therapeutic (like many of those filed for injector pens), should not be counted in the decision-making over what is included in the FDA’s Orange Book, and that manufacturers could be punished by regulators for attempting to have these smaller-scale patents approved by the USPTO.

Read More: Big Pharma’s Patent Abuses Are Fueling the Drug Pricing Crisis

There are some signs that government officials are taking some steps towards restricting patent manipulation: On Nov. 7, the U.S. Federal Trade Commission (FTC) announced an intended appraisal of more than 100 patents for medications and devices listed in the FDA’s orange book. According to an agency press release, the list of patents that the FTC flagged as potentially improper include those for various inhalers, EpiPen injectors, and medicated eye drops. The FTC’s current list of patents under scrutiny doesn’t include insulin products, but the changes it causes could affect them. The agency has given drugmakers with products on the list 30 days to withdraw or amend their Orange Book patents before they’ll face potential legal challenges for any failures to meet current standards. It’s possible that could trigger pharma companies to evaluate their patents in other areas—including insulin—as well.

Britain’s medicines regulator has authorized the world’s first gene therapy treatment for sickle cell disease, in a move that could offer relief to thousands of people with the crippling disease in the U.K.

In a statement on Thursday, the Medicines and Healthcare Regulatory Agency said it approved Casgevy, the first medicine licensed using the gene editing tool CRISPR, which won its makers a Nobel prize in 2020.

The agency approved the treatment for patients with sickle cell disease and thalassemia who are 12 years old and over. Casgevy is made by Vertex Pharmaceuticals (Europe) Ltd. and CRISPR Therapeutics. To date, bone marrow transplants, extremely arduous procedures that come with very unpleasant side effects, have been the only long-lasting treatment.

“The future of life-changing cures resides in CRISPR based (gene-editing) technology,” said Dr. Helen O’Neill of University College London.

“The use of the word ‘cure’ in relation to sickle cell disease or thalassemia has, up until now, been incompatible,” she said in a statement, calling the MHRA’s approval of gene therapy “a positive moment in history.”

Both sickle cell disease and thalassemia are caused by mistakes in the genes that carry hemoglobin, the protein in red blood cells that carry oxygen.

In people with sickle cell — which is particularly common in people with African or Caribbean backgrounds — a genetic mutation causes the cells to become crescent-shaped, which can block blood flow and cause excruciating pain, organ damage, stroke and other problems.

In people with thalassemia, the genetic mutation can cause severe anemia. Patients typically require blood transfusions every few weeks, and injections and medicines for their entire life. Thalassemia predominantly affects people of South Asian, Southeast Asian and Middle Eastern heritage.

The new medicine, Casgevy, works by targeting the problematic gene in a patient’s bone marrow stem cells so that the body can make properly functioning hemoglobin.

Patients first receive a course of chemotherapy, before doctors take stem cells from the patient’s bone marrow and use genetic editing techniques in a laboratory to fix the gene. The cells are then infused back into the patient for a permanent treatment. Patients must be hospitalized at least twice — once for the collection of the stem cells and then to receive the altered cells.

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Britain’s regulator said its decision to authorize the gene therapy for sickle cell disease was based on a study done on 29 patients, of whom 28 reported having no severe pain problems for at least one year after being treated. In the study for thalassemia, 39 out of 42 patients who got the therapy did not need a red blood cell transfusion for at least a year afterwards.

Gene therapy treatments can cost millions of dollars and experts have previously raised concerns that they could remain out of reach for the people who would benefit most.

Last year, Britain approved a gene therapy for a fatal genetic disorder that had a list price of £2.8 million ($3.5 million). England’s National Health Service negotiated a significant confidential discount to make it available to eligible patients.

Vertex Pharmaceuticals said it had not yet established a price for the treatment in Britain and was working with health authorities “to secure reimbursement and access for eligible patients as quickly as possible.”

In the U.S., Vertex has not released a potential price for the therapy, but a report by the nonprofit Institute for Clinical and Economic Review said prices up to around $2 million would be cost-effective. By comparison, research earlier this year showed medical expenses for current sickle cell treatments, from birth to age 65, add up to about $1.6 million for women and $1.7 million for men.

Medicines and treatments in Britain must be recommended by a government watchdog before they are made freely available to patients in the national health care system.

Casgevy is currently being reviewed by the U.S. Food and Drug Administration; the agency is expected to make a decision early next month, before considering another sickle cell gene therapy.

Millions of people around the world, including about 100,000 in the U.S., have sickle cell disease. It occurs more often among people from places where malaria is or was common, like Africa and India, and is also more common in certain ethnic groups, such as people of African, Middle Eastern and Indian descent. Scientists believe being a carrier of the sickle cell trait helps protect against severe malaria.

AP Science Writer Laura Ungar in Louisville, Kentucky contributed to this report.

The Associated Press Health and Science Department receives support from the Howard Hughes Medical Institute’s Science and Educational Media Group. The AP is solely responsible for all content.

Popular weight loss drugs have dominated news headlines and social media, mostly for their ability to help people shed pounds and control diabetes. But now there is evidence that one of the drugs, semaglutide, can also help reduce the risk of dying from heart disease in some patients. The drug semaglutide is sold under the brand names Wegovy, Ozempic, and Rybelsus. This trial, however, only studied the effects of Wegovy, which is semaglutide at 2.4mg in injectable form, and currently approved for weight management. The results of a much-anticipated study, sponsored by semaglutide’s maker Novo Nordisk, investigating the drug’s effects on the heart were presented at the annual meeting of the American Heart Association in Philadelphia and published in the New England Journal of Medicine.

The study involved more than 17,000 people without diabetes but with a history of heart attack, stroke, or circulatory symptoms, who were also overweight or obese, with a body mass index of 27 or greater. Because they had a history of heart issues, most were on medications to treat risk factors like high blood pressure, high cholesterol, and clotting. To learn what effect losing weight could have on reducing the risk of dying from heart disease—on top of controlling those risk factors—the researchers randomly assigned half of the volunteers to receive the drug semaglutide, which was approved in 2021 to treat people who are overweight and obese, while the other half received a placebo.

After more than three years, the scientists, led by Dr. A. Michael Lincoff, professor of medicine at the Cleveland Clinic, found that the people who received semaglutide lost about 9% of their body weight, compared to less than 1% in the placebo group. Those receiving semaglutide also reduced their risk of having a heart attack or stroke, or dying from a heart event, by 20%, compared to those receiving the placebo. The result generated applause from the standing room-only audience packed into one of the main auditoriums for the American Heart Association meeting.

“It’s been established that obesity and being overweight increases the risk of cardiovascular events, but while the standard of care includes treating risk factors such as hypertension, diabetes, and high cholesterol with medications, the risk factor of obesity and being overweight have not been something we have been able to effectively treat in the past,” Lincoff tells TIME. “Now for some patients we have another pathway, an additional modifiable risk factor that can be treated with semaglutide.”

“This is an entirely new pathway to harness, of addressing obesity and its metabolic complications,” says Dr. Amit Khera, director of the Preventive Cardiology Program at the University of Texas Southwestern Medical Center. “The fact that we have a new treatment avenue for patients with cardiovascular disease is incredibly exciting, and welcome.”

“The results are astounding,” says Dr. Holly Lofton, director of the medical weight management program at NYU Langone Health, who led the study at one of the more than 800 sites involved in the trial. “I think this will change prescribing practices.”

The patients in the study represent a larger cohort of 6.6 million people in the U.S. who might benefit from the drug, said Dr. Ania Jastreboff, associate professor of medicine and director of the Yale Obesity Research Center at Yale School of Medicine during a presentation at the conference.

Lincoff notes that while the trial found a link between the weight loss drug and a lower risk of heart events, the effect may be more complex than a simple correlation between pounds dropped and risk lowered.“It isn’t the amount of weight loss that influences [heart] risk,” he says. The difference in heart events between the two groups began to emerge quickly, after about a month of weekly treatment, but the weight loss occurred gradually and didn’t max out until about a year. “The benefit was not necessarily proportional or driven by how much weight was lost,” he explains. In fact, the heart benefits were similar for people no matter what they weighed at the start of the study, or how much they lost during the trial.

More research will be needed to clarify exactly how the drug is affecting the heart, but it’s possible that changing levels of GLP-1 could also trigger physiological changes that directly affect the heart. “We know from other studies that excess adiposity can have direct effects on heart and blood vessel cells, so the drugs may be affecting excess fat cells, which promote inflammation and can promote atherosclerosis and increase the stickiness of blood [through clotting], all of which increase the risk of heart events,” says Lincoff.

Jastreboff agrees. “If we treat obesity, then we improve things like hypertension, hyperlipidemia, and inflammation, and we see benefits for all different types of diseases,” she said during a briefing at the conference.

The data provides the strongest reason yet to start treating heart patients who are overweight or obese, just as doctors address high blood pressure, excess cholesterol, and diabetes in patients. “It’s always nice to have another tool in the toolbox,” says Dr. Sean Heffron, assistant professor of medicine at the NYU Center for the Prevention of Cardiovascular Disease. Many heart experts are impressed that the 20% drop in heart events was on top of reductions they already experienced from being treated with the current standard of care, including aspirin, statins to lower cholesterol, and medications to control hypertension. “We are literally leaping forward from the past to the future at a watershed brought on by highly effective obesity medications,” Jastreboff said.

Dr. Bruno Manno, a clinical professor of cardiology at NYU Langone who was in the audience for the presentation, says “I see about 20 people a day, half of whom would qualify for this [treatment]. The results make a very compelling argument for sure for treating them.” He says, however, that the high cost of the drug—more than $1000 for a month’s supply—as well as lack of coverage by insurance companies and shortages in the supply of semaglutide are the biggest barriers to seeing heart patients benefit from the medication. “If the cost and availability issues weren’t there, there wouldn’t be an issue at all in treatment of the people who are a fit for this medication,” he says.

One change that could potentially convince more insurers to cover the drug is adding heart benefits to its label. Novo Nordisk has filed a request to the U.S. Food and Drug Administration to update the label for semaglutide (Wegovy) to include the fact that among people with a BMI of 27 or higher, and with a history of heart disease, the medication can reduce the risk of additional heart events. The FDA has granted priority review of the request, and is expected to make its final decision in six months.

In the meantime, the success of the study naturally raises the question about whether the drug should be used in people without a history of heart attack or stroke, to help them avoid a heart event to begin with, rather than withholding the medication until people experience a heart event. “Scientifically, the medical benefit is likely to be similar,” says Lincoff. “But logistically doing that study will be difficult.”

Even in the absence of such a study, Lofton notes that combining the results of this trial with the results from previous studies of semaglutide that included people who were overweight or obese without a history of heart problems, may justify using the drug to help people avoid having a heart event in the first place. “I think the astute preventive cardiologist or primary care doctor would consider that someone is a candidate for semaglutide to help them lose weight if they are overweight or obese and have a strong family history of heart disease or other risk factors,” she says. In fact, the drug is already approved for people who are overweight or obese, but their doctors can now tell them that there is a possibility that in addition to losing weight, they might also reduce their risk of heart disease. However, there isn’t hard data to document that yet. “They may say that the drug is not intended to treat cholesterol or blood pressure or other heart risk factors, but they may also see benefits there,” she says.

As encouraging as the data is, Khera cautions that the results should be interpreted carefully, and aren’t a license to dismiss the importance of changing diet and exercise habits to lower heart disease risk. He notes that the population in the study were people with existing heart disease, but that ideally, people should avoid experiencing heart events in the first place. “You don’t want to wait until you develop cardiovascular disease,” he says. “It’s not about making a choice between lifestyle modifications or these medicines. It never is, and never will be. It should start with lifestyle changes first, and when needed, this medicine can now be a helpful additional option.”

Addressing access and availability will be the next hurdles for semaglutide. Novo Nordisk has increased manufacturing to meet the already explosive demand for the drug, but with a new population of patients now eligible for the medication, supply constraints likely won’t ease until at least 2024.

Weight loss drugs have dominated the headlines over the past year, and now there’s a new medication that may be the most effective one yet.

On Nov. 11, the U.S. Food and Drug Administration (FDA) approved tirzepatide (which will be sold under the brand name Zepbound), to treat overweight and obesity. Made by Eli Lilly and Co., the drug is already approved, in different doses, for type 2 diabetes, as Mounjaro, and its effectiveness in those patients is due in part to its weight loss effects.

About 70% of Americans are overweight, with a body mass index (BMI) between 27 and 30, or obese, with a BMI over 30—which increase the risk of a host of other health problems, including heart disease, diabetes, osteoarthritis and more. Yet there really haven’t been effective medications to treat obesity. Since its approval in 2021, semaglutide, made by Novo Nordisk and sold as Wegovy, has helped enough people lose a significant amount of weight to prompt more doctors to see overweight and obesity as chronic conditions, similar to high blood pressure, diabetes, and high cholesterol, all of which are treated with medications.

Read more: Should We End Obesity?

Lilly submitted studies to the FDA showing that tirzepatide helped people who were overweight or obese and did not have diabetes to lose about 18% of their body weight compared to people receiving a placebo. In previous studies, those with diabetes lost about 12% of their weight on average. (In comparison, people without diabetes lost an average of 15% in semaglutide trials.)

That might not sound like that much, but it’s still more than people typically lose by changing diet and exercise alone, which generally leads to body weight drops in the single digit percentages. That’s why obesity experts say these drugs could represent a turning point in weight management.

Patients inject Zepbound once a week in progressively higher doses over up to 20 weeks to achieve the maximum dose of 15 mg. The FDA noted that the drug can cause side effects such as nausea, vomiting, hair loss, and reflux; in the animal studies, the drug was linked to thyroid tumors but it’s not clear if the same risk occurs in people, so the agency warned that people with a history of thyroid cancer should not take the medication.

Tirzepatide belongs to a group of drugs that mimics incretins, which are hormones released by the gut in response to food. Incretins signal cells in the pancreas to secrete insulin, which breaks down the glucose in food and helps to regulate glucose in the blood. Without enough incretins, blood sugar levels can escalate, contributing to weight gain, diabetes, and a number of other metabolic conditions. While scientists have known for about 50 years that the incretins perform this function, they have not been able to mimic the hormones as a treatment, because they are too short lived, says Dr. Daniel Skovronsky, chief scientific and medical officer and president of Lilly Research Laboratories, who was part of the team that developed tirzepatide. Over decades, Lilly’s scientists, along with others in the pharmaceutical industry, worked to find ways to stabilize and extend the longevity of incretins in the body. After years of experimenting with various incretins in mice, Skovronsky and his team found that combining them could improve both glucose and weight control. Tirzepatide is a combination of two of the most effective of these incretins: glucagon-like peptide 1 (GLP-1) and glucose dependent insulinotropic polypeptide (GIP). It’s the first dual-acting weight loss drug of its kind. (Semaglutides, including Ozempic and Wegovy, target a single incretin, GLP-1).

The combination proved to be a potent one. In the first safety study of tirzepatide, which involved a small number of patients with type 2 diabetes, the team already saw considerable weight loss. So in 2016, when the larger study was completed and showed a dramatic weight loss of about 12% to 13% of body weight among patients, he says “I wasn’t surprised, because I remember thinking, ‘this is exactly what I predicted from the animal studies.’ I was really excited to advance tirzepatide forward not just for type 2 diabetes but also for chronic weight management or obesity.”

Based on those results, the drug was eventually launched six years later in 2022, for people with type 2 diabetes, the fastest development in the company’s history. Given the drug’s dramatic effect on weight, Lilly decided to study and pursue FDA approval for overweight patients and those with obesity as well. Ultimately, the FDA did not approve the drug as a weight loss option for people who want to shed a few pounds. Doctors can prescribe the drug only for people who are overweight, with a BMI of 27 to 30, if they have at least one additional risk factor associated with their excess weight, such as high blood pressure or high cholesterol, or for anyone with a BMI of 30 or more, which is considered obese.

The market for such a drug is huge, of course, not just in the U.S. but across the world, where about half of the global population is expected to be overweight or obese in the next few decades. In a conversation with TIME weeks before the approval, Lilly’s CEO Dave Ricks said that treating obesity could also result in huge cost savings for the health care system, which is currently treating the expensive consequences of obesity—from heart disease and diabetes to kidney disease and joint issues. “Overweight and obesity is a huge drag on the cost of health care in this country, contributing over $400 billion in direct costs, and over $1 trillion in indirect costs,” he said.

Read more: Column: Ozempic Can’t Fix America’s Obesity Crisis

The FDA’s approval of tirzepatide, following the approval of semaglutide in 2021, gives doctors and patients two of the most potent drugs yet to treat weight loss. Having a growing formulary of effective weight loss drugs may help doctors, patients and, most importantly, insurance companies to recognize obesity as a chronic medical problem, rather than as a consequence of poor lifestyle choices. There’s evidence that the medication could supplement diet and exercise changes; in a Lilly study of people who were overweight or obese but did not have diabetes who took Zepbound, those who started with diet and exercise alone and lost  on average 6.9% body weight, and then added the drug lost an additional 21% body weight over 72 weeks, compared to a placebo group that on average gained back 3.3% body weight.

Doses of Zepbound should be available in coming weeks at pharmacies, company executives said during a briefing after the approval. But access may still be a challenge for some. Zepbound will cost 20% less than its main competitor Wegovy for those with insurance coverage, but both drugs remain expensive, at just over $1,000 for a month’s supply, and not all insurers cover obesity treatments. Lilly announced that those whose insurance plans do not cover anti-obesity treatments will be eligible for a 50% discount. 

Ricks said that the company is developing next-generation incretins as well, and is in late stage trials with a weight loss drug that combines three of them. Lilly’s scientists are also developing an oral form of tirzepatide that would not require injections. “It’s quite likely that obesity, like other chronic conditions, is heterogenous, and different people have different causes of their obesity,” says Skovronsky. “That’s why we need different therapies that could address different types of obesity. We’re not there yet today, but that’s the future.”

The world is entering a new era of vaccines. Following the success of COVID-19 mRNA shots, scientists have a far greater capacity to tailor shots to a virus’s structure, putting a host of new vaccines on the horizon.

The most recent arrivals are several new immunizations against respiratory syncytial virus, or RSV.

These shots are welcome since RSV can be dangerous, even deadly, in the very old and very young. But the shots, produced by Pfizer and GlaxoSmithKline, are also expensive, costing about $300 for those directed at adults, and up to $1,000 for one of the shots, a monoclonal antibody rather than a traditional vaccine, intended for babies. Many older vaccines cost pennies.

And in part because of the high cost, there is a shortage of RSV shots for infants, leading the U.S. Centers for Disease Control and Prevention to issue a warning for doctors to prioritize the most vulnerable babies.

The advent of these new drugs is forcing the U.S. to face anew questions it has long sidestepped: How much should an immunization cost that will possibly be given—maybe yearly—to millions of Americans? Also, given the U.S. is one of two countries that permit direct advertising to consumers: How can we ensure the shots get into the arms of people who will truly benefit and not those of people who seek it out as a result of scary marketing, at great expense?

Already, ads on television and the internet show active retirees playing pickleball or going to art galleries whose lives are “cut short by RSV.” This helps explain the lines for the shot at my local pharmacy.

The indiscriminate use of expensive shots could strain both public and private insurers’ already tight budgets.

The risk of RSV for infants

Other developed countries have deliberate strategies for deciding which vulnerable groups need a particular vaccine and how much to pay for it. The U.S. does not, and as specialized vaccines proliferate, public programs and private insurers will need to grapple with how to use and finance shots that can be hugely beneficial for some but will waste precious health dollars if taken by all.

A seasonal viral illness, RSV can cause hospitalization or, in rare cases, death in babies and in people ages 75 or older, as well as those with serious underlying medical conditions such as heart disease or cancer. For most people who get RSV, it plays out as a cold; you’ve likely had RSV many times without knowing it.

But RSV puts about 2% of babies under age 1 in the hospital and annually kills between 100 and 300 of those under 6 months, because their immune systems are immature and their airways too narrow to tolerate the inflammation. Merely having a bad case of RSV in young childhood increases the risk of long-term asthma.

Read More: Why it Took So Long to Get an RSV Vaccine

That’s why Dr. Barney Graham, the scientist who spent decades at the government’s National Institutes for Health perfecting the basic science that led to the current shots, said “the most obvious use is in infants,” not adults.

That’s also why a consortium of European countries, trying to figure out how best to use these vaccines without breaking the bank, focused first on babies and determining a sensible price. Though more of the very old may die of RSV, the years of life lost are much greater for the very young. (Babies can get the monoclonal antibody shot directly or gain protection through a traditional vaccine given to the mother near the end of pregnancy, conferring immunity through the womb.)

Examining the cost-utility of the vaccine, a team of European researchers looked at scenarios where the price was what the team termed “very expensive” —which they put at above €75 (about $80) – or “cheapish” which they put at below €25(about $27), says Philippe Beutels, professor in health economics at the University of Antwerp, who led the group.

While the calculus varies somewhat from country to country, the group concluded generally that if the price was at the high end, it was not cost effective. That meant, he said, “we should not give either kind of shot and stick to current practice” of treating sick infants—who usually do fine—with supportive care.

The calculation will be used by countries such as Belgium, U.K., Denmark, Finland, and the Netherlands to negotiate a set price for the two infant shots, followed by decisions on which version should be offered. “If the monoclonal antibody is €100 and the vaccine €10, then the vaccine would be preferable,” Beutels says.

They have not yet considered how to distribute the vaccines to adults—considered less pressing—because studies show that RSV rarely causes severe disease in adults who live outside of care settings, such as a nursing home.

Letting the market decide who gets drugs

Why did the U.S. focus first on older adults, while Europe is more concerned about RSV in infants?

In the U.S., the drug makers had a financial incentive: Roughly 3.7 million babies are born each year, while there are about 75 million Americans ages 60 and older—the group for whom the two adult vaccines were approved. And about half of children get their vaccines through the Vaccines for Children program, which negotiates discounted prices.

Also, babies can get vaccinated only by their clinicians. Adults can walk into local drug stores for the shots, and pharmacies are only too happy to have the business.

But which older adults truly benefit from the shot? Studies presented by the manufacturers to the U.S. Food and Drug Administration for approval in a population of generally healthy people 60 and older, so that’s the group to whom they may be marketed. And marketed they are, even though the studies didn’t show the shots staved off hospitalization or death in people ages 60 to 75.

Read More: How to Avoid the Tripledemic of Respiratory Diseases This Winter

That led to what some have called a “narrow” endorsement from the CDC’s Advisory Committee on Immunization Practices (ACIP) for people 60 to 75: Patients in that age range could get the shot after “shared clinical decision-making” with a health provider.

In part because of this fuzzy, conditional endorsement, it is likely some Americans 60 and over with commercial insurance are finding that their insurers won’t cover it. Under Obamacare, insurers are generally required to cover at no cost vaccines that are recommended by the ACIP.

(In late September, the ACIP recommended immunization of all babies with either the antibody or the maternal vaccine. Insurers have a year to commence coverage and many have been dragging their feet because of the high price.)

A patchwork strategy

There are better and more equitable ways to steer the shots into the arms of those who need it, rather than simply administering it to those who have the “right” insurance or, swayed by advertising, can pay. For example, insurers, including Medicare, could be required to cover only those ages 60 to 75 who have a prescription from a doctor, indicating shared decision-making has occurred.

During the pandemic emergency, the federal government purchased all COVID-19 vaccines in bulk at a negotiated price, initially below $20 a shot, and distributed them nationally. If, to protect public health, we want vaccines to get into the arms of all who benefit, that’s a more cohesive strategy than the patchwork one used now.

Vaccines are miraculous, and it’s great news that they now exist to prevent serious illness and death from RSV. But using such novel vaccines wisely—directing them to the people who need them at a price they can afford—will be key. Otherwise, the cost to the health system, and to patients, could undermine this big medical win.

Alzheimer’s patients now have more options than ever for treating their disease— two drugs are approved to treat the causes of Alzheimer’s, and the U.S. Food and Drug Administration is currently considering approving another, which could be available next year. Many researchers are starting to focus on how to get the most out of these treatments: how to identify people who will benefit the most, how long people need to be treated, and how to measure the effect of the drugs. They are also exploring whether these drugs could not only slow, but maybe even prevent some of the more damaging effects of the disease.

At the annual Clinical Trials on Alzheimer’s Disease conference in Boston, Eisai and Biogen, makers of the most recently approved drug, lecanemab (Leqembi), as well as Eli Lilly, maker of donanemab, which the U.S. Food and Drug Administration (FDA) is currently reviewing for possible approval by the end of the year, reported on their latest studies. Eisai provided additional data on longer-term use of its drug, as well as on a new formulation that would make it easier for patients to take than the current hour-long IV infusion once every two weeks. Lilly shared new data from its final phase of testing that showed patients’ ability to execute daily tasks improved, as did their performance on memory, orientation, and judgment tests while taking the experimental drug, compared to those receiving a placebo.

The FDA approved lecanemab in January, based on data showing that IV infusions once every two weeks for a year and a half delayed cognitive decline by 27% in those receiving the drug compared to people getting a placebo. At the Boston conference this week, Eisai presented encouraging data on a new formulation of its drug—one that doctors or patients themselves can inject once a week rather than receive through an hour-long infusion once a month. In a group of 72 patients who received lecanemab for the first time as an injection, and 322 patients from the original study who switched from the IV infusion to the injections for six months, PET scans showed that the injections led to a 14% greater reduction in amyloid compared to those who had received IV infusions after six months. That, according to Eisai, may be because the injections result in a higher blood concentration of the drug by about 11% compared to the IV infusion. “We think the [injection] formulation will really help patients in terms of making it more convenient and not having to go to infusion centers,” says Dr. Michael Irizarry, senior vice president of clinical research at Eisai. He says the company plans to request that the FDA approve the injections by the end of March 2024.

Eisai also provided more detailed and extended data suggesting that lecanemab works best when it is used as early in the disease as possible, and that the benefits continued to 24 months, six months beyond the original study. 

Experts believe that tau, which forms tangles that can compromise brain neurons, tends to accumulate after amyloid plaques have caused damage, so people with low levels of tau are still at the relatively early stages of disease. In Eisai’s latest study, researchers looked at a subset of the patients in the company’s original study who had very low levels of tau. In this group, 76% of those getting lecanemab showed no decline in tests of memory, orientation, or judgment; or in their engagement in social activities and hobbies; or in their personal care habits compared to 55% of those getting placebo. Even more encouraging, among these people with early disease, 60% of those getting the drug showed improvement in their test scores compared to 28% in the placebo group.

“This supports starting earlier in treatment for people who have symptomatic Alzheimer’s in order to maintain or improve their cognitive function,” says Irizarry.

Lilly saw similar benefits in early-stage patients who received its experimental drug, donanemab. In its study, all patients received tau PET scans, so the researchers could distinguish between those at earlier and later stages of disease. Among people with low-to-medium amounts of tau in the brain, 36% of those receiving the drug showed slowing of disease progression as measured by tests of memory, orientation, judgment, and measures of social engagement. 

Delaying the onset of symptoms is essential—not just for patients, who can remain independent for longer, but for their caregivers as well. Lilly’s data showed that most patients in the study who were taking donanemab were able to remain at the same level of dependency at which they started the trial—for most that meant they needed some reminders about daily activities, such as taking their medicine or putting out the trash or other housekeeping tasks. But they didn’t progress quickly into more dependent stages in which they would need help getting dressed, remembering to eat, and executing other critical skills. In fact, about a quarter of the people taking the drug did not move on to becoming more dependent, compared to 50% of those taking placebo during the 18 month study.

Both Eisai’s and Lilly’s data confirm that starting treatment earlier gives the medications more opportunity to clear amyloid build up and prevent damage to brain neurons. That means it might even be possible to not only delay some of the more advanced symptoms of Alzheimer’s related to memory and cognition, but to also prevent them. Dr. John Sims, senior medical director at Lilly, says that the company anticipates that donanemab will not be a life-long prescription—but that patients could use it to either remove or reach an acceptable level of amyloid in the brain, which can then be monitored as they come off the drug for periods of time. “The hypothesis we are working on is that it’s much better to monitor the disease because it is a really slow process overall, and maybe some people may never need another treatment,” he says. If these results are supported by continued follow up, that would mean focusing even more on how best to diagnose patients at the earliest stages of disease, before memory or other cognitive symptoms appear. “The data show that the most optimal benefit occurs if people are treated as early as possible,” says Irizarry.

Experts in the field are already working on honing the criteria for diagnosing Alzheimer’s, and developing guidelines for even non-dementia experts such as primary care physicians to make it easier to distinguish when people have the condition, and which patients would benefit from treatment—as early as possible.