Science
Contributor: By loosening standards, the FDA isn’t doing rare-disease patients any favors
If you’re faced with a serious disease, you better hope it’s not a rare one.
After an often tortuous path to diagnosis, people with rare diseases are likely to find that good treatment options don’t exist and none is on the horizon. Many of these conditions are poorly understood, and conducting studies in tiny patient populations can be practically impossible. Most drugs won’t pan out, and those that do will have little demand and financial payoff, no matter how beneficial they are. Drug companies usually direct their attention elsewhere.
Recognizing these challenges, policymakers have worked since the 1980s to encourage rare-disease drug development. They’ve earmarked federal research funding, established dedicated programs at the Food and Drug Administration, extended protection against competition to help secure profits, and awarded lucrative incentives for rare pediatric disease drugs. Still, 95% of rare diseases, which affect an estimated 30 million Americans, lack any approved therapy.
Some blame the FDA. They say the agency is too rigid, imposing impossible requirements and demanding unreasonable proof of effectiveness and safety for rare disease drugs. Some suggest patients would be better off if the FDA just got out of the way — not only for rare disease treatments, but also more broadly.
The current administration now seems determined to do just that, at least for products that fit the “Make America Healthy Again” agenda, like stem cells and psychedelics (never mind recent intrusions on COVID vaccines and abortion drugs).
Large swaths of FDA experts have been DOGE’d or otherwise forced out of the agency. Commissioner Martin Makary has proposed approving drugs based just on their scientific plausibility, while the agency’s chief medical and scientific officer pledged to “take action at the first sign of promise for rare diseases” — potentially making treatments available far sooner, even though many drugs that look promising at the start turn out not to work.
Just last month, the FDA announced approval of a drug the commissioner claimed would help “hundreds of thousands of kids” with autism, not based on a clinical trial but on published case reports of 40 patients with a potentially related condition — alarmingly and unprecedentedly accepting anecdotes as evidence of efficacy.
The call to disarm the FDA is coming from inside the house.
Criticism of the agency’s gatekeeping is certainly not new, but critics are especially vocal now. Banking on expectations that the Trump administration would break through perceived red tape, they are calling on the White House and new FDA leadership to approve rare disease drugs with far less attention to safety and effectiveness than to keeping companies financially interested in developing rare disease treatments and bringing them to market.
It can be reasonable to assess rare disease drugs differently as usual market-driven incentives often fail to yield treatment options. That’s why the FDA has been remarkably flexible about these approvals for decades. Sure, the FDA sometimes says no — but what if the drugs it rejects just weren’t any good?
Ideally, you want to see a drug’s effectiveness replicated in at least two studies to be confident in the results. For drugs approved to treat common diseases (outside of cancer), that replication is typical. But only 13% of approved rare disease drugs (again outside of cancer) relied on more than one robust clinical trial to show they work. Recent FDA policy has made clear that this single-study approach will be the rule for rare disease drugs and potentially for other conditions going forward.
Rare disease drugs are also increasingly granted “accelerated approval,” a pathway that allows drugs for serious diseases to be approved based on predicted rather than proven benefit. Companies must complete required studies after approval, but the FDA has allowed drugs to stay on the market even if these studies fail. This happened for a recent gene therapy for Duchenne muscular dystrophy, a therapy that was later linked to patient deaths.
Even outside accelerated approval, the agency sometimes approves drugs that miss the targets chosen in advance to prove the drug works. A recent study found this happens in 1 of 10 approvals, about half of which were for rare disease.
Despite this flexibility, criticism continues. Rather than taking FDA’s refusal to approve a drug as a critical warning sign, these decisions are often met with the assumption that the FDA must be wrong.
Take the agency’s recent action on elamipretide for Barth syndrome, an ultra-rare, life-threatening genetic disorder characterized by heart, muscle and immune system abnormalities that affects about 300 patients globally.
Given the tiny patient population, Stealth BioTherapeutics, the company developing elamipretide, conducted a trial in just 12 people, which failed to show the drug worked. Some patients continued in an extended version of the trial and appeared to perform better on tests of walking distance and fatigue. However, the FDA reasonably worried this might be because of patients’ awareness that they were receiving the drug, leading to a placebo effect.
After reviewing the evidence, the FDA issued a letter in May 2025 refusing to approve elamipretide. Recognizing the need for flexibility, however, the agency left the door open to approval based on a new, unverified measure of patient benefit: improved muscle strength in the knee. In September, following substantial public criticism from patient advocates and members of Congress, the FDA granted the drug accelerated approval. Stealth will now have to complete another study to see whether the treatment really helps patients — but even if that study fails, the agency may not withdraw approval.
Even if elamipretide fails to pan out, one might wonder what harm lies in just approving it. Maybe it can provide some hope to patients who have nothing else, while encouraging companies not to abandon rare diseases.
The problem is this: Those who criticize the FDA for setting the bar too high shrug off trial data that fail to show benefit, arguing that it doesn’t mean the drug is ineffective. But it is very hard to prove that a drug doesn’t work. If that were the standard, FDA reviewers should just close up shop, leaving a universal “approved” stamp for any drug that appears not to kill patients.
When it’s working well, FDA approval signals to patients (and their doctors and insurers) “this drug has been shown to work” — or at least “this drug has been shown very likely to work.” If FDA approval means anything less, such as “this drug has not been shown not to work,” it fails to serve patients, leaving them no better off than if they were browsing unproven dietary supplements on Amazon. They might even be worse off, if duped into relying on FDA approval as a meaningful indicator of benefit.
Rare disease patients, like all patients, should have drugs that work. The burden must be on companies to prove that their drugs do. Shifting or altering that burden by changing FDA approval standards won’t help, but other changes might. For example, policymakers could improve existing legal approaches that allow patients with serious diseases to try investigational drugs that aren’t yet approved. The federal government could also increase support for the research needed to understand, diagnose and treat rare disease, helping companies focus on the most promising targets and minimizing failures. Unfortunately, the Trump administration’s ongoing decimation of federal health agencies and research instead sets back rare disease science.
Public trust in authorities like the FDA is already depleted. Demanding that the agency greenlight more rare disease drugs, evidence be damned, will make this problem worse — and likely won’t leave rare disease patients better off. Rather than blaming the FDA, the policymakers, companies and patient advocates should be doing all they can to get better drugs in front of the agency’s reviewers.
Holly Fernandez Lynch is a senior fellow at the Leonard Davis Institute of Health Economics at the University of Pennsylvania, where she is also an associate professor of medical ethics and law. Reshma Ramachandran is a family medicine physician and assistant professor at Yale School of Medicine, where she co-directs the Yale Collaboration for Regulatory Rigor, Integrity and Transparency.
Science
There were 13 full-service public health clinics in L.A. County. Now there are 6
Because of budget cuts, the Los Angeles County Department of Public Health has ended clinical services at seven of its public health clinic sites.
As of Feb. 27, the county is no longer providing services such as vaccinations, sexually transmitted infection testing and treatment, or tuberculosis diagnosis and specialty TB care at the affected locations, according to county officials and a department fact sheet.
The sites losing clinical services are Antelope Valley in Lancaster; the Center for Community Health (Leavy) in San Pedro, Curtis R. Tucker in Inglewood, Hollywood-Wilshire, Pomona, Dr. Ruth Temple in South Los Angeles, and Torrance. Services will continue to be provided by the six remaining public health clinics, and through nearby community clinics.
The changes are the result of about $50 million in funding losses, according to official county statements.
“That pushed us to make the very difficult decision to end clinical services at seven of our sites,” said Dr. Anish Mahajan, chief deputy director of the L.A. County Department of Public Health.
Mahajan said the department selected clinics with relatively lower patient volumes. Over the last month, he said, the department has sent letters to patients about the changes, and referred them to unaffected county clinics, nearby federally qualified health centers or other community providers. According to Mahajan, for tuberculosis patients, particularly those requiring directly observed therapy, public health nurses will continue visiting patients.
Public health clinics form part of the county’s healthcare safety net, serving low-income residents and those with limited access to care. Officials said that about half of the patients the county currently sees across its clinics are uninsured.
Mahajan noted that the clinics were established decades ago, before the Affordable Care Act expanded Medi-Cal coverage and increased the number of federally qualified health centers. He said that as more residents gained access to primary care, utilization at some county-run clinics declined.
“Now that we have a more sophisticated safety net, people often have another place to go for their full range of care,” he said.
Still, the closures have unsettled providers who work closely with local vulnerable populations.
“I hate to see any services that serve our at-risk and homeless community shut down,” said Mark Hood, chief executive of Union Rescue Mission in downtown Los Angeles. “There’s so much need out there, so it always is going to create hardship for the people that actually need the help the most.”
Union Rescue Mission does not receive government funding for its healthcare services, Hood said. The mission’s clinics are open not only to shelter guests, up to 1,000 people nightly, but also to people living on the streets who walk in seeking care.
Its dental clinic alone sees nearly 9,000 patients a year, Hood said.
“We haven’t seen it yet, but I expect in the coming days and weeks we’ll see more people coming through our doors looking for help,” he said. “They’re going to have to find help somewhere.” Hood said women experiencing homelessness are especially vulnerable when preventive care, including sexual and reproductive health services, becomes harder to access.
County officials said staffing impacts so far have been managed through reassignment rather than layoffs. Roughly 200 to 300 positions across the department have been eliminated amid funding cuts, officials said, though many were vacant. About 120 employees whose positions were affected have been reassigned; according to Mahajan, no one has been laid off.
The clinic closures come amid broader fiscal uncertainty. Mahajan said that due to the Trump administration’s “Big Beautiful Bill,” Los Angeles County could lose $2.4 billion over the next several years. That funding, he said, supports clinics, hospitals and community clinic partners now absorbing patients who previously went to the clinics that closed on Feb. 27.
In response, the L.A. County Board of Supervisors has backed a proposed half-cent sales tax measure that would generate hundreds of millions of dollars annually for healthcare and public health services. Voters are expected to consider the measure in June.
Science
Mobile clinic brings mammograms to women on Skid Row
Sharon Horton stepped through the door of a sky-blue mobile clinic and onto a Skid Row sidewalk. She wore a yellow knit beanie, gold hoop earrings and the relieved grin of a woman who has finally checked a mammogram off her to-do list.
It had been years since her last breast cancer screening procedure. This one, which took place in City of Hope’s Cancer Prevention and Screening mobile clinic, was faster and easier. The staff was kind. The machine that X-rayed her breast was more comfortable than the cold hard contraption she remembered.
Relatively speaking, of course — it was still a mammogram.
“It’s like, OK, let me go already!” Horton, 68, said with a laugh.
The clinic was parked on South San Pedro Street in front of Union Rescue Mission, the nonprofit shelter where Horton resides. Within a week, City of Hope, a cancer research hospital, would share the results with Horton and Dr. Mary Marfisee, the mission’s family medical services director. If the mammogram detected anything of concern, they’d map out a treatment plan from there.
Naureen Sayani, 47, a resident of Union Rescue Mission, left, discusses her medical history with Adriana Galindo, a medical assistant, before getting a mammogram on last week.
(Kayla Bartkowski / Los Angeles Times)
“It’s very important to take care of your health, and you need to get involved in everything that you can to make your life a better life,” said Horton, who is looking forward to a forthcoming move into Section 8 housing.
Horton was one of the first patients of a new women’s health initiative from UCLA’s Homeless Healthcare Collaborative at Union Rescue Mission. Staffed by third-year UCLA Medical School students and led by Marfisee, a UCLA assistant clinical professor of family medicine, the clinic treats mission residents as well as unhoused people living in the surrounding neighborhood.
The new cancer screening project arrives at a time of dire financial pressures on county public health services.
Citing rising costs and a $50-million reduction in federal, state and local grant and contract income, the Los Angeles County Department of Public Health on Feb. 27 ended services at seven of 13 public clinics that provide vaccines, tests and treatment for sexually transmitted diseases and other services to housed and unhoused county residents.
Although Union Rescue Mission’s own funding comes mainly from private sources and is less imperiled by public cuts, the 135-year-old shelter expects the need for its services to rise, Chief Executive Mark Hood said.
Even as unsheltered homelessness declined for the last two years across Los Angeles County, the unsheltered population on Skid Row — long seen as the epicenter of the region’s homelessness crisis — grew 9% in 2024, the most recent year for which census data are available.
For many local women navigating daily concerns over housing, food and personal safety, “their own health is not a priority,” Marfisee said.
Those whose problems have become too serious to ignore face daunting obstacles to care. Marfisee recalled one patient who came to her with a lump in her breast and no identification.
In order to get a mammogram, Marfisee explained, the woman first needed to obtain a birth certificate, and then a state-issued identification card. Then she needed to enroll in Medi-Cal. After that, clinic staff helped her find a primary care physician who could order the imaging test.
Given the barriers to preventative care, homeless women die from breast cancer at nearly twice the rate of securely housed women, a 2019 study found. Marfisee’s own survey of the mission’s female residents found that nearly 90% were not up to date on recommended cancer screenings like mammograms and pap smears, which detect early cervical cancer.
To address this gap, Marfisee — a dogged patient advocate — reached out to City of Hope. The Duarte-based research and treatment center unveiled in March 2024 its first mobile cancer screening clinic, a moving van-sized clinic on wheels that it deploys to food banks and health centers, as well as to companies offering free mammograms as an employee benefit.
“In true Dr. Mary fashion, she saw the vision,” said Jessica Thies, the mobile screening program’s regional nursing director. After working through some logistical hurdles, the mission and City of Hope secured a date for the van’s first visit.
The next challenge was getting the word out to patients. Marfisee and her students walked through the surrounding neighborhood, went cot to cot in the women’s dorm and held two informational sessions in December and January to answer patients’ questions.
At the sessions, the team walked through the basics of who should get a mammogram (women age 40 or older, those with a family history of breast cancer) and the procedure itself. (“Like a tortilla maker?” one woman asked skeptically after hearing a description of the mammography unit.)
The medical students were able to dispel rumors some women had heard: The test doesn’t damage breast tissue, nor do the X-rays increase cancer risk. Others questioned a mammogram’s value: What good was it knowing they had cancer if they couldn’t get follow-up care?
On this latter point, Marfisee is determined not to let patients fall through the cracks.
Thirteen patients received mammograms at the van’s first visit on Wednesday. Within a week, City of Hope will contact patients with their results and send them to Marfisee and her team. She is already mentally mapping the next steps should any patient have a situation that requires a biopsy or further imaging: working with their case manager at the mission, calling in favors, wrangling with any insurance the patient might have.
“It’ll be a good fight,” Marfisee said, as residents in the adjacent cafeteria carried trays of sloppy joes and burgers to their lunch tables. “But we’ll just keep asking for help and get it done.”
Science
Can fire-resistant homes be sexy? ‘You be the judge,’ says this Palisades architect
At first glance, it looks like nothing more than a charming Spanish-revival, quintessentially Californian home — but this Pacific Palisades rebuild is constructed like a tank.
Every exterior wall of the steel-framed home is a foot-thick, fire-resistant barricade. The home is connected to a satellite fire monitoring service. Should a fire start in town, sturdy metal shutters descend to cover every window. An exterior sprinkler system can pump 40,000 gallons of water from giant tanks hidden behind the shrubs in the property’s yard. If the cameras and heat sensors around the house detect danger, the system can envelop the home in over 1,000 gallons of fire retardant and hundreds of gallons of fire-suppressing foam.
Palisades resident and architect Ardie Tavangarian is so confident in his design that he even asked the fire department if they could start a controlled fire on the property to test it all out. (They said no.)
Tavangarian built a career designing multimillion-dollar luxury homes in Los Angeles, but after the Palisades fire destroyed 13 of his works — including his family’s home — he found another calling: how to design a house that can handle what the Santa Monica Mountains throw at it. And how to do it quickly and affordably.
Water tanks form part of a backup water supply in a newly built fire-resistant home in Pacific Palisades.
“Nature is so powerful,” he said, sitting on a couch in the new house, which he built for his adult twin daughters. “We are guests living in that environment and expecting, ‘Oh, nature is going to be really kind to me.’ No, it’s not. It does what it’s supposed to do.”
Tavangarian watched the Jan. 1 Lachman fire from his property not far from here; a week later that fire rekindled, grew into the Palisades fire, and burned through his house. But the painful details of the fire — the missteps of the fire department, the empty reservoir — didn’t matter when it came to deciding how to rebuild, he said. The reality is, many fires have burned in these mountains. Many more will.
A sprinkler on the roof is part of a house-wide sprinkler system.
For the architect, who has spent much of his 45-year career designing for luxury, hardening a home against wildfire has brought a new kind of luxury to his homes: peace of mind.
It’s a sentiment that resonates with fire survivors: Tavangarian says he’s received considerable interest from other property owners in the Palisades looking to rebuild their houses.
The metal shutters and advanced outdoor sprinkler system are the flashiest parts of Tavangarian’s home hardening project, and the efficacy of these adaptations is still up for debate. Because the measures have not yet been widely adopted, there are few studies exploring how much or little they protect homes in real-world fires.
Architect Ardie Tavangarian inside the house he designed.
Anecdotal evidence has indicated the effectiveness of sprinklers can vary significantly based on the setup and the conditions during the fire. Extreme wind, for example, can make them less effective. Lab studies have generally found shutters can reduce the risk of windows shattering.
These measures aren’t cheap, either. Sprinkler systems can cost north of $100,000, for example. However, Tavangarian said when all was said and done, the home he built for his daughters cost around $700 per square foot — less than what Palisades residents said they expected to pay, but more than what Altadena residents expected for their rebuilds.
Tavangarian also hopes to see insurers increasingly consider the home-hardening measures property owners take when writing policies, which he said could potentially offset the extra cost in a decade or less. As he explored getting insurance for the new home, one insurer quoted him $80,000 a year. After he convinced the company to visit the property, it lowered the quote to just $13,000, he said.
The house includes metal heat shields that can drop down if a fire approaches.
The home also has essentially all of the other less flashy — but much cheaper and well-proven — home hardening measures recommended by fire professionals: The underside of the roof’s overhang is closed off — a common place embers enter a home. The roof, where burning embers can accumulate, is made of fire-resistant material. The windows, vulnerable to shattering in extreme heat, are made of a toughened glass. There is virtually no vegetation within the first five feet of the home.
When asked if he felt he had compromised on design, comfort or aesthetics for the extra protection — one of the many concerns Californians have with the state’s draft “Zone Zero” requirements that may significantly limit vegetation within five feet of a home — Tavangarian simply said, “You be the judge.”
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