An At-Home Contagiousness Test for COVID-19 Already Exists. Why Can’t We Use It?
Kira Peikoff was the editor-in-chief of Leaps.org from 2017 to 2021. As a journalist, her work has appeared in The New York Times, Newsweek, Nautilus, Popular Mechanics, The New York Academy of Sciences, and other outlets. She is also the author of four suspense novels that explore controversial issues arising from scientific innovation: Living Proof, No Time to Die, Die Again Tomorrow, and Mother Knows Best. Peikoff holds a B.A. in Journalism from New York University and an M.S. in Bioethics from Columbia University. She lives in New Jersey with her husband and two young sons. Follow her on Twitter @KiraPeikoff.
You're lying in bed late at night, the foggy swirl of the pandemic's 8th month just beginning to fall behind you, when you detect a slight tickle at the back of your throat.
"If half of people choose to use these tests every other day, then we can stop transmission faster than a vaccine can."
Suddenly fully awake, a jolt of panicked electricity races through your body. Has COVID-19 come for you? In the U.S., answering this simple question is incredibly difficult.
Now, you might have to wait for hours in line in your car to get a test for $100, only to find out your result 10-14 days later -- much too late to matter in stopping an outbreak. Due to such obstacles, a recent report in JAMA Internal Medicine estimated that 9 out of 10 infections in the U.S. are being missed.
But what if you could use a paper strip in the privacy of your own home, like a pregnancy test, and find out if you are contagious in real time?
e25 Bio, a small company in Cambridge, Mass., has already created such a test and it has been sitting on a lab bench, inaccessible, since April. It is an antigen test, which looks for proteins on the outside of a virus, and can deliver results in about 15 minutes. Also like an over-the-counter pregnancy test, e25 envisions its paper strips as a public health screening tool, rather than a definitive diagnostic test. People who see a positive result would be encouraged to then seek out a physician-administered, gold-standard diagnostic test: the more sensitive PCR.
Typically, hospitals and other health facilities rely on PCR tests to diagnose viruses. This test can detect small traces of genetic material that a virus leaves behind in the human body, which tells a clinician that the patient is either actively infected with or recently cleared that virus. PCR is quite sensitive, meaning that it is able to detect the presence of a virus' genetic material very accurately.
But although PCR is the gold-standard for diagnostics, it's also the most labor-intensive way to test for a virus and takes a relatively long time to produce results. That's not a good match for stopping super-spreader events during an unchecked pandemic. PCR is also not great at identifying the infected people when they are most at risk of potentially transmitting the virus to others.
That's because the viral threshold at which PCR can detect a positive result is so low, that it's actually too sensitive for the purposes of telling whether someone is contagious.
"The majority of time someone is PCR positive, those [genetic] remnants do not indicate transmissible virus," epidemiologist Michael Mina recently Tweeted. "They indicate remnants of a recently cleared infection."
To stop the chain of transmission for COVID-19, he says, "We need a more accurate test than PCR, that turns positive when someone is able to transmit."
In other words, we need a test that is better at detecting whether a person is contagious, as opposed to whether a small amount of virus can be detected in their nose or saliva. This kind of test is especially critical given the research showing that asymptomatic and pre-symptomatic people have high viral loads and are spreading the virus undetected.
The critical question for contagiousness testing, then, is how big a dose of SARS-CoV-2, the virus that causes COVID, does it take to infect most people? Researchers are still actively trying to answer this. As Angela Rasmussen, a coronavirus expert at Columbia University, told STAT: "We don't know the amount that is required to cause an infection, but it seems that it's probably not a really, really small amount, like measles."
Amesh Adalja, an infectious disease physician and a senior scholar at the Johns Hopkins University Center for Health Security, told LeapsMag: "It's still unclear what viral load is associated with contagiousness but it is biologically plausible that higher viral loads, in general, are associated with more efficient transmission especially in symptomatic individuals. In those without symptoms, however, the same relationship may not hold and this may be one of the reasons young children, despite their high viral loads, are not driving outbreaks."
"Antigen tests work best when there's high viral loads. They're catching people who are super spreaders."
Mina and colleagues estimate that widespread use of weekly cheap, rapid tests that are 100 times less sensitive than PCR tests would prevent outbreaks -- as long as the people who are positive self-isolate.
So why can't we buy e25Bio's test at a drugstore right now? Ironically, it's barred for the very reason that it's useful in the first place: Because it is not sensitive enough to satisfy the U.S. Food and Drug Administration, according to the company.
"We're ready to go," says Carlos-Henri Ferré, senior associate of operations and communications at e25. "We've applied to FDA, and now it's in their hands."
The problem, he said, is that the FDA is evaluating applications for antigen tests based on criteria for assessing diagnostics, like PCR, even when the tests serve a different purpose -- as a screening tool.
"Antigen tests work best when there's high viral loads," Ferré says. "They're catching people who are super spreaders, that are capable of continuing the spread of disease … FDA criteria is for diagnostics and not this."
FDA released guidance on July 29th -- 140 days into the pandemic -- recommending that at-home tests should perform with at least 80 percent sensitivity if ordered by prescription, and at least 90 percent sensitivity if purchased over the counter. "The danger of a false negative result is that it can contribute to the spread of COVID-19," according to an FDA spokesperson. "However, oversight of a health care professional who reviews the results, in combination with the patient's symptoms and uses their clinical judgment to recommend additional testing, if needed, among other things, can help mitigate some risks."
Crucially, the 90 percent sensitivity recommendation is judged upon comparison to PCR tests, meaning that if a PCR test is able to detect virus in 100 samples, the at-home antigen test would need to detect virus in at least 90 of those samples. Since antigen tests only detect high viral loads, frustrated critics like Mina say that such guidance is "unreasonable."
"The FDA at this moment is not understanding the true potential for wide-scale frequent testing. In some ways this is not their fault," Mina told LeapsMag. "The FDA does not have any remit to evaluate tests that fall outside of medical diagnostic testing. The proposal I have put forth is not about diagnostic testing (leave that for symptomatic cases reporting to their physician and getting PCR tests)....Daily rapid tests are not about diagnosing people and they are not about public health surveillance and they are not about passports to go to school, out to dinner or into the office. They are about reducing population-level transmission given a similar approach as vaccines."
A reasonable standard, he added, would be to follow the World Health Organization's Target Product Profiles, which are documents to help developers build desirable and minimally acceptable testing products. "A decent limit," Mina says, "is a 70% or 80% sensitivity (if they truly require sensitivity as a metric) to detect virus at Ct values less than 25. This coincides with detection of the most transmissible people, which is important."
(A Ct value is a type of measurement that corresponds inversely to the amount of viral load in a given sample. Researchers have found that Ct values of 13-17 indicate high viral load, whereas Ct values greater than 34 indicate a lack of infectious virus.)
"We believe this should be an at-home test, but [if FDA approval comes through] the first rollout is to do this in laboratories, hospitals, and clinics."
"We believe that population screening devices have an immediate place and use in helping beat the virus," says Ferré. "You can have a significant impact even with a test at 60% sensitivity if you are testing frequently."
When presented with criticism of its recommendations, the FDA indicated that it will not automatically deny any at-home test that fails to meet the 90 percent sensitivity guidance.
"FDA is always open to alternative proposals from developers, including strategies for serial testing with less sensitive tests," a spokesperson wrote in a statement. "For example, it is possible that overall sensitivity of the strategy could be considered cumulatively rather than based on one-time testing….In the case of a manufacturer with an at-home test that can only detect people with COVID-19 when they have a high viral load, we encourage them to talk with us so we can better understand their test, how they propose to use it, and the validation data they have collected to support that use."
However, the FDA's actions so far conflict with its stated openness. e25 ended up adding a step to the protocol in order to better meet FDA standards for sensitivity, but that extra step—sending samples to a laboratory for results—will undercut the test's ability to work as an at-home screening tool.
"We believe this should be an at-home test, but [if FDA approval comes through] the first rollout is to do this in laboratories, hospitals, and clinics," Ferré says.
According to the FDA, no test developers have approached them with a request for an emergency use authorization that proposes an alternate testing paradigm, such as serial testing, to mitigate test sensitivity below 80 percent.
From a scientific perspective, antigen tests like e25Bio's are not the only horse in the race for a simple rapid test with potential for at-home use. CRISPR technology has long been touted as fertile ground for diagnostics, and in an eerily prescient interview with LeapsMag in November, CRISPR pioneer Feng Zhang spoke of its potential application as an at-home diagnostic for an infectious disease specifically.
"I think in the long run it will be great to see this for, say, at-home disease testing, for influenza and other sorts of important public health [concerns]," he said in the fall. "To be able to get a readout at home, people can potentially quarantine themselves rather than traveling to a hospital and then carrying the risk of spreading that disease to other people as they get to the clinic."
Zhang's company Sherlock Biosciences is now working on scaled-up manufacturing of a test to detect SARS CoV-2. Mammoth Biosciences, which secured funding from the National Institutes of Health's Rapid Acceleration of Diagnostics program, is also working on a CRISPR diagnostic for SARS CoV-2. Both would check the box for rapid testing, but so far not for at-home testing, as they would also require laboratory infrastructure to provide results.
If any at-home tests can clear the regulatory hurdles, they would also need to be manufactured on a large scale and be cheap enough to entice people to actually use them. In the world of at-home diagnostics, pregnancy tests have become the sole mainstream victor because they're simple to use, small to carry, easy to interpret, and costs about seven or eight dollars at any ubiquitous store, like Target or Walmart. By comparison, the at-home COVID collection tests that don't even offer diagnostics—you send away your sample to an external lab—all cost over $100 to take just one time.
For the time being, the only available diagnostics for COVID require a lab or an expensive dedicated machine to process. This disconnect could prolong the world's worst health crisis in a century.
"Daily rapid tests have enormous potential to sever transmission chains and create herd effects similar to herd immunity," Mina says. "We all recognize that vaccines and infections can result in herd immunity when something around half of people are no longer susceptible.
"The same thing exists with these tests. These are the intervention to stop the virus. If half of people choose to use these tests every other day, then we can stop transmission faster than a vaccine can. The technology exists, the theory and mathematics back it up, the epidemiology is sound. There is no reason we are not approaching this as strongly as we would be approaching vaccines."
--Additional reporting by Julia Sklar
Kira Peikoff was the editor-in-chief of Leaps.org from 2017 to 2021. As a journalist, her work has appeared in The New York Times, Newsweek, Nautilus, Popular Mechanics, The New York Academy of Sciences, and other outlets. She is also the author of four suspense novels that explore controversial issues arising from scientific innovation: Living Proof, No Time to Die, Die Again Tomorrow, and Mother Knows Best. Peikoff holds a B.A. in Journalism from New York University and an M.S. in Bioethics from Columbia University. She lives in New Jersey with her husband and two young sons. Follow her on Twitter @KiraPeikoff.
Can AI chatbots help with eating disorders?
Her name was Tessa and she was there to help. That’s what Sharon Maxwell read, anyway. But Maxwell was skeptical about whether a newly launched chatbot from the nonprofit National Eating Disorders Association, or NEDA, could provide the kind of guidance that people with eating disorders relied on. Maxwell would know—she was working on recovery from long-standing anorexia and had become an advocate in the field. So Maxwell took a deep breath and asked, “Hi Tessa. How do you support folks with eating disorders?”
Tessa’s reply was immediate. “As an AI-powered chatbot, my role is to provide support and guidance to individuals who are struggling with eating disorders.”
So far, so good. Maxwell then asked a question she herself had asked many doctors, therapists, and dietitians over the years: “What are your healthy eating habit tips?” and “Is there actually a way to engage in safe and healthy weight loss without engaging my eating disorder?”
Then everything went off the rails. Tessa told Maxwell an unequivocal yes, and that “it’s important to approach weight loss with a balanced and realistic mindset,” and recommended eating whole foods and lean proteins to create a 500-1000 calorie per day deficit that would lead to a loss of 1-2 pounds per week. To most people, the advice sounds anodyne, but alarm bells sounded in Maxwell’s head.
“This is actively going to feed eating disorders,” Maxwell says. “Having a chatbot be the direct response to someone reaching out for support for an eating disorder instead of the helpline seems careless.”
“The scripts that are being fed into the chatbot are only going to be as good as the person who’s feeding them.” -- Alexis Conason.
According to several decades of research, deliberate weight loss in the form of dieting is a serious risk for people with eating disorders. Maxwell says that following medical advice like what Tessa prescribed was what triggered her eating disorder as a child. And Maxwell wasn’t the only one who got such advice from the bot. When eating disorder therapist Alexis Conason tried Tessa, she asked the AI chatbot many of the questions her patients had. But instead of getting connected to resources or guidance on recovery, Conason, too, got tips on losing weight and “healthy” eating.
“The scripts that are being fed into the chatbot are only going to be as good as the person who’s feeding them,” Conason says. “It’s important that an eating disorder organization like NEDA is not reinforcing that same kind of harmful advice that we might get from medical providers who are less knowledgeable.”
Maxwell’s post about Tessa on Instagram went viral, and within days, NEDA had scrubbed all evidence of Tessa from its website. The furor has raised any number of issues about the harm perpetuated by a leading eating disorder charity and the ongoing influence of diet culture and advice that is pervasive in the field. But for AI experts, bears and bulls alike, Tessa offers a cautionary tale about what happens when a still-immature technology is unfettered and released into a vulnerable population.
Given the complexity involved in giving medical advice, the process of developing these chatbots must be rigorous and transparent, unlike NEDA’s approach.
“We don’t have a full understanding of what’s going on in these models. They’re a black box,” says Stephen Schueller, a clinical psychologist at the University of California, Irvine.
The health crisis
In March 2020, the world dove head-first into a heavily virtual world as countries scrambled to try and halt the pandemic. Even with lockdowns, hospitals were overwhelmed by the virus. The downstream effects of these lifesaving measures are still being felt, especially in mental health. Anxiety and depression are at all-time highs in teens, and a new report in The Lancet showed that post-Covid rates of newly diagnosed eating disorders in girls aged 13-16 were 42.4 percent higher than previous years.
And the crisis isn’t just in mental health.
“People are so desperate for health care advice that they'll actually go online and post pictures of [their intimate areas] and ask what kind of STD they have on public social media,” says John Ayers, an epidemiologist at the University of California, San Diego.
For many people, the choice isn’t chatbot vs. well-trained physician, but chatbot vs. nothing at all.
I know a bit about that desperation. Like Maxwell, I have struggled with a multi-decade eating disorder. I spent my 20s and 30s bouncing from crisis to crisis. I have called suicide hotlines, gone to emergency rooms, and spent weeks-on-end confined to hospital wards. Though I have found recovery in recent years, I’m still not sure what ultimately made the difference. A relapse isn't improbably, given my history. Even if I relapsed again, though, I don’t know it would occur to me to ask an AI system for help.
For one, I am privileged to have assembled a stellar group of outpatient professionals who know me, know what trips me up, and know how to respond to my frantic texts. Ditto for my close friends. What I often need is a shoulder to cry on or a place to vent—someone to hear and validate my distress. What’s more, my trust in these individuals far exceeds my confidence in the companies that create these chatbots. The Internet is full of health advice, much of it bad. Even for high-quality, evidence-based advice, medicine is often filled with disagreements about how the evidence might be applied and for whom it’s relevant. All of this is key in the training of AI systems like ChatGPT, and many AI companies remain silent on this process, Schueller says.
The problem, Ayers points out, is that for many people, the choice isn’t chatbot vs. well-trained physician, but chatbot vs. nothing at all. Hence the proliferation of “does this infection make my scrotum look strange?” questions. Where AI can truly shine, he says, is not by providing direct psychological help but by pointing people towards existing resources that we already know are effective.
“It’s important that these chatbots connect [their users to] to provide that human touch, to link you to resources,” Ayers says. “That’s where AI can actually save a life.”
Before building a chatbot and releasing it, developers need to pause and consult with the communities they hope to serve.
Unfortunately, many systems don’t do this. In a study published last month in the Journal of the American Medical Association, Ayers and colleagues found that although the chatbots did well at providing evidence-based answers, they often didn’t provide referrals to existing resources. Despite this, in an April 2023 study, Ayers’s team found that both patients and professionals rated the quality of the AI responses to questions, measured by both accuracy and empathy, rather highly. To Ayers, this means that AI developers should focus more on the quality of the information being delivered rather than the method of delivery itself.
Many mental health professionals have months-long waitlists, which leaves individuals to deal with illnesses on their own.
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The human touch
The mental health field is facing timing constraints, too. Even before the pandemic, the U.S. suffered from a shortage of mental health providers. Since then, the rates of anxiety, depression, and eating disorders have spiked even higher, and many mental health professionals report waiting lists that are months long. Without support, individuals are left to try and cope on their own, which often means their condition deteriorates even further.
Nor do mental health crises happen during office hours. I struggled the most late at night, long after everyone else had gone to bed. I needed support during those times when I was most liable to hurt myself, not in the mornings and afternoons when I was at work.
In this sense, a 24/7 chatbot makes lots of sense. “I don't think we should stifle innovation in this space,” Schueller says. “Because if there was any system that needs to be innovated, it's mental health services, because they are sadly insufficient. They’re terrible.”
But before building a chatbot and releasing it, Tina Hernandez-Boussard, a data scientist at Stanford Medicine, says that developers need to pause and consult with the communities they hope to serve. It requires a deep understanding of what their needs are, the language they use to describe their concerns, existing resources, and what kinds of topics and suggestions aren’t helpful. Even asking a simple question at the beginning of a conversation such as “Do you want to talk to an AI or a human?” could allow those individuals to pick the type of interaction that suits their needs, Hernandez-Boussard says.
NEDA did none of these things before deploying Tessa. The researchers who developed the online body positivity self-help program upon which Tessa was initially based created a set of online question-and-answer exercises to improve body image. It didn’t involve generative AI that could write its own answers. The bot deployed by NEDA did use generative AI, something that no one in the eating disorder community was aware of before Tessa was brought online. Consulting those with lived experience would have flagged Tessa’s weight loss and “healthy eating” recommendations, Conason says.
The question for healthcare isn’t whether to use AI, but how.
NEDA did not comment on initial Tessa’s development and deployment, but a spokesperson told Leaps.org that “Tessa will be back online once we are confident that the program will be run with the rule-based approach as it was designed.”
The tech and therapist collaboration
The question for healthcare isn’t whether to use AI, but how. Already, AI can spot anomalies on medical images with greater precision than human eyes and can flag specific areas of an image for a radiologist to review in greater detail. Similarly, in mental health, AI should be an add-on for therapy, not a counselor-in-a-box, says Aniket Bera, an expert on AI and mental health at Purdue University.
“If [AIs] are going to be good helpers, then we need to understand humans better,” Bera says. That means understanding what patients and therapists alike need help with and respond to.
One of the biggest challenges of struggling with chronic illness is the dehumanization that happens. You become a patient number, a set of laboratory values and test scores. Treatment is often dictated by invisible algorithms and rules that you have no control over or access to. It’s frightening and maddening. But this doesn’t mean chatbots don’t have any place in medicine and mental health. An AI system could help provide appointment reminders and answer procedural questions about parking and whether someone should fast before a test or a procedure. They can help manage billing and even provide support between outpatient sessions by offering suggestions for what coping skills to use, the best ways to manage anxiety, and point to local resources. As the bots get better, they may eventually shoulder more and more of the burden of providing mental health care. But as Maxwell learned with Tessa, it’s still no replacement for human interaction.
“I'm not suggesting we should go in and start replacing therapists with technologies,” Schueller says. Instead, he advocates for a therapist-tech collaboration. “The technology side and the human component—these things need to come together.”
Questions remain about new drug for hot flashes
Vascomotor symptoms (VMS) is the medical term for hot flashes associated with menopause. You are going to hear a lot more about it because a company has a new drug to sell. Here is what you need to know.
Menopause marks the end of a woman’s reproductive capacity. Normal hormonal production associated with that monthly cycle becomes erratic and finally ceases. For some women the transition can be relatively brief with only modest symptoms, while for others the body's “thermostat” in the brain is disrupted and they experience hot flashes and other symptoms that can disrupt daily activity. Lifestyle modification and drugs such as hormone therapy can provide some relief, but women at risk for cancer are advised not to use them and other women choose not to do so.
Fezolinetant, sold by Astellas Pharma Inc. under the product name Veozah™, was approved by the Food and Drug Administration (FDA) on May 12 to treat hot flashes associated with menopause. It is the first in a new class of drugs called neurokinin 3 receptor antagonists, which block specific neurons in the brain “thermostat” that trigger VMS. It does not appear to affect other symptoms of menopause. As with many drugs targeting a brain cell receptor, it must be taken continuously for a few days to build up a good therapeutic response, rather than working as a rescue product such as an asthma inhaler to immediately treat that condition.
Hot flashes vary greatly and naturally get better or resolve completely with time. That contributes to a placebo effect and makes it more difficult to judge the outcome of any intervention. Early this year, a meta analysis of 17 studies of drug trials for hot flashes found an unusually large placebo response in those types of studies; the placebo groups had an average of 5.44 fewer hot flashes and a 36 percent reduction in their severity.
In studies of fezolinetant, the drug recently approved by the FDA, the placebo benefit was strong and persistent. The drug group bested the placebo response to a statistically significant degree but, “If people have gone from 11 hot flashes a day to eight or seven in the placebo group and down to a couple fewer ones in the drug groups, how meaningful is that? Having six hot flashes a day is still pretty unpleasant,” says Diana Zuckerman, president of the National Center for Health Research (NCHR), a health oriented think tank.
“Is a reduction compared to placebo of 2-3 hot flashes per day, in a population of women experiencing 10-11 moderate to severe hot flashes daily, enough relief to be clinically meaningful?” Andrea LaCroix asked a commentary published in Nature Medicine. She is an epidemiologist at the University of California San Diego and a leader of the MsFlash network that has conducted a handful of NIH-funded studies on menopause.
Questions Remain
LaCroix and others have raised questions about how Astellas, the company that makes the new drug, handled missing data from patients who dropped out of the clinical trials. “The lack of detailed information about important parameters such as adherence and missing data raises concerns that the reported benefits of fezolinetant very likely overestimate those that will be observed in clinical practice," LaCroix wrote.
In response to this concern, Anna Criddle, director of global portfolio communications at Astellas, wrote in an email to Leaps.org: “…a full analysis of data, including adherence data and any impact of missing data, was submitted for assessment by [the FDA].”
The company ran the studies at more than 300 sites around the world. Curiously, none appear to have been at academic medical centers, which are known for higher quality research. Zuckerman says, "When somebody is paid to do a study, if they want to get paid to do another study by the same company, they will try to make sure that the results are the results that the company wants.”
Criddle said that Astellas picked the sites “that would allow us to reach a diverse population of women, including race and ethnicity.”
A trial of a lower dose of the drug was conducted in Asia. In March 2022, Astellas issued a press release saying it had failed to prove effectiveness. No further data has been released. Astellas still plans to submit the data, according to Criddle. Results from clinical trials funded by the U.S. goverment must be reported on clinicaltrials.gov within one year of the study's completion - a deadline that, in this case, has expired.
The measurement scale for hot flashes used in the studies, mild-moderate-severe, also came in for criticism. “It is really not good scale, there probably isn’t a broad enough range of things going on or descriptors,” says David Rind. He is chief medical officer of the Institute for Clinical and Economic Review (ICER), a nonprofit authority on new drugs. It conducted a thorough review and analysis of fezolinestant using then existing data gathered from conference abstracts, posters and presentations and included a public stakeholder meeting in December. A 252-page report was published in January, finding “considerable uncertainty about the comparative net health benefits of fezolinetant” versus hormone therapy.
Questions surrounding some of these issues might have been answered if the FDA had chosen to hold a public advisory committee meeting on fezolinetant, which it regularly does for first in class medicines. But the agency decided such a meeting was unnecessary.
Cost
There was little surprise when Astellas announced a list price for fezolinetant of $550 a month ($6000 annually) and a program of patient assistance to ease out of pocket expenses. The company had already incurred large expenses.
In 2017 Astellas purchased the company that originally developed fezolinetant for $534 million plus several hundred million in potential royalties. The drug company ran a "disease awareness” ad, Heat on the Street, hat aired during the Super Bowl in February, where 30 second ads cost about $7 million. Industry analysts have projected sales to be $1.9 billion by 2028.
ICER’s pre-approval evaluation said fezolinetant might "be considered cost-effective if priced around $2,000 annually. ... [It]will depend upon its price and whether it is considered an alternative to MHT [menopause hormone treatment] for all women or whether it will primarily be used by women who cannot or will not take MHT."
Criddle wrote that Astellas set the price based on the novelty of the science, the quality of evidence for the drug and its uniqueness compared to the rest of the market. She noted that an individual’s payment will depend on how much their insurance company decides to cover. “[W]e expect insurance coverage to increase over the course of the year and to achieve widespread coverage in the U.S. over time.”
Leaps.org wrote to and followed up with nine of the largest health insurers/providers asking basic questions about their coverage of fezolinetant. Only two responded. Jennifer Martin, the deputy chief consultant for pharmacy benefits management at the Department of Veterans Affairs, said the agency “covers all drugs from the date that they are launched.” Decisions on whether it will be included in the drug formulary and what if any copays might be required are under review.
“[Fezolinetant] will go through our standard P&T Committee [patient and treatment] review process in the next few months, including a review of available efficacy data, safety data, clinical practice guidelines, and comparison with other agents used for vasomotor symptoms of menopause," said Phil Blando, executive director of corporate communications for CVS Health.
Other insurers likely are going through a similar process to decide issues such as limiting coverage to women who are advised not to use hormones, how much copay will be required, and whether women will be required to first try other options or obtain approvals before getting a prescription.
Rind wants to see a few years of use before he prescribes fezolinetant broadly, and believes most doctors share his view. Nor will they be eager to fill out the additional paperwork required for women to participate in the Astellas patient assistance program, he added.
Safety
Astellas is marketing its drug by pointing out risks of hormone therapy, such as a recent paper in The BMJ, which noted that women who took hormones for even a short period of time had a 24 percent increased risk of dementia. While the percentage was scary, the combined number of women both on and off hormones who developed dementia was small. And it is unclear whether hormones are causing dementia or if more severe hot flashes are a marker for higher risk of developing dementia. This information is emerging only after 80 years of hundreds of millions of women using hormones.
In contrast, the label for fezolinetant prohibits “concomitant use with CYP1A2 inhibitors” and requires testing for liver and kidney function prior to initiating the drug and every three months thereafter. There is no human or animal data on use in a geriatric population, defined as 65 or older, a group that is likely to use the drug. Only a few thousand women have ever taken fezolinetant and most have used it for just a few months.
Options
A woman seeking relief from symptoms of menopause would like to see how fezolintant compares with other available treatment options. But Astellas did not conduct such a study and Andrea LaCroix says it is unlikely that anyone ever will.
ICER has come the closest, with a side-by-side analysis of evidence-based treatments and found that fezolinetant performed quite similarly and modestly as the others in providing relief from hot flashes. Some treatments also help with other symptoms of menopause, which fezolinetant does not.
There are many coping strategies that women can adopt to deal with hot flashes; one of the most common is dressing in layers (such as a sleeveless blouse with a sweater) that can be added or subtracted as conditions require. Avoiding caffeine, hot liquids, and spicy foods is another common strategy. “I stopped drinking hot caffeinated drinks…for several years, and you get out of the habit of drinking them,” says Zuckerman.
LaCroix curates those options at My Meno Plan, which includes a search function where you can enter your symptoms and identify which treatments might work best for you. It also links to published research papers. She says the goal is to empower women with information to make informed decisions about menopause.