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Contributor: By loosening standards, the FDA isn’t doing rare-disease patients any favors

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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).

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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?

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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.

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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.

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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.

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Can fire-resistant homes be sexy? ‘You be the judge,’ says this Palisades architect

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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.

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“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 a roof.

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.

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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.

Ardie Tavangarian stands inside a house.

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.

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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.

A living room inside a fire-resistant house, with metal heat shields drawn over the windows.

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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Commentary: My toothache led to a painful discovery: The dental care system is full of cavities as you age

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Commentary: My toothache led to a painful discovery: The dental care system is full of cavities as you age

I had a nagging toothache recently, and it led to an even more painful revelation.

If you X-rayed the state of oral health care in the United States, particularly for people 65 and older, the picture would be full of cavities.

“It’s probably worse than you can even imagine,” said Elizabeth Mertz, a UC San Francisco professor and Healthforce Center researcher who studies barriers to dental care for seniors.

Mertz once referred to the snaggletoothed, gap-filled oral health care system — which isn’t really a system at all — as “a mess.”

But let me get back to my toothache, while I reach for some painkiller. It had been bothering me for a couple of weeks, so I went to see my dentist, hoping for the best and preparing for the worst, having had two extractions in less than two years.

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Let’s make it a trifecta.

My dentist said a molar needed to be yanked because of a cellular breakdown called resorption, and a periodontist in his office recommended a bone graft and probably an implant. The whole process would take several months and cost roughly the price of a swell vacation.

I’m lucky to have a great dentist and dental coverage through my employer, but as anyone with a private plan knows, dental insurance can barely be called insurance. It’s fine for cleanings and basic preventive routines. But for more complicated and expensive procedures — which multiply as you age — you can be on the hook for half the cost, if you’re covered at all, with annual payout caps in the $1,500 range.

“The No. 1 reason for delayed dental care,” said Mertz, “is out-of-pocket costs.”

So I wondered if cost-wise, it would be better to dump my medical and dental coverage and switch to a Medicare plan that costs extra — Medicare Advantage — but includes dental care options. Almost in unison, my two dentists advised against that because Medicare supplemental plans can be so limited.

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Sorting it all out can be confusing and time-consuming, and nobody warns you in advance that aging itself is a job, the benefits are lousy, and the specialty care you’ll need most — dental, vision, hearing and long-term care — are not covered in the basic package. It’s as if Medicare was designed by pranksters, and we’re paying the price now as the percentage of the 65-and-up population explodes.

So what are people supposed to do as they get older and their teeth get looser?

A retired friend told me that she and her husband don’t have dental insurance because it costs too much and covers too little, and it turns out they’re not alone. By some estimates, half of U.S. residents 65 and older have no dental insurance.

That’s actually not a bad option, said Mertz, given the cost of insurance premiums and co-pays, along with the caps. And even if you’ve got insurance, a lot of dentists don’t accept it because the reimbursements have stagnated as their costs have spiked.

But without insurance, a lot of people simply don’t go to the dentist until they have to, and that can be dangerous.

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“Dental problems are very clearly associated with diabetes,” as well as heart problems and other health issues, said Paul Glassman, associate dean of the California Northstate University dentistry school.

There is one other option, and Mertz referred to it as dental tourism, saying that Mexico and Costa Rica are popular destinations for U.S. residents.

“You can get a week’s vacation and dental work and still come out ahead of what you’d be paying in the U.S.,” she said.

Tijuana dentist Dr. Oscar Ceballos told me that roughly 80% of his patients are from north of the border, and come from as far away as Florida, Wisconsin and Alaska. He has patients in their 80s and 90s who have been returning for years because in the U.S. their insurance was expensive, the coverage was limited and out-of-pocket expenses were unaffordable.

“For example, a dental implant in California is around $3,000-$5,000,” Ceballos said. At his office, depending on the specifics, the same service “is like $1,500 to $2,500.” The cost is lower because personnel, office rent and other overhead costs are cheaper than in the U.S., Ceballos said.

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As we spoke by phone, Ceballos peeked into his waiting room and said three patients were from the U.S. He handed his cellphone to one of them, San Diegan John Lane, who said he’s been going south of the border for nine years.

“The primary reason is the quality of the care,” said Lane, who told me he refers to himself as 39, “with almost 40 years of additional” time on the clock.

Ceballos is “conscientious and he has facilities that are as clean and sterile and as medically up to date as anything you’d find in the U.S.,” said Lane, who had driven his wife down from San Diego for a new crown.

“The cost is 50% less than what it would be in the U.S.,” said Lane, and sometimes the savings is even greater than that.

Come this summer, Lane may be seeing even more Californians in Ceballos’ waiting room.

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“Proposed funding cuts to the Medi-Cal Dental program would have devastating impacts on our state’s most vulnerable residents,” said dentist Robert Hanlon, president of the California Dental Assn.

Dental student Somkene Okwuego smiles after completing her work on patient Jimmy Stewart, 83, who receives affordable dental work at the Ostrow School of Dentistry of USC on the USC campus in Los Angeles on February 26, 2026.

(Genaro Molina / Los Angeles Times)

Under Proposition 56’s tobacco tax in 2016, supplemental reimbursements to dentists have been in place, but those increases could be wiped out under a budget-cutting proposal. Only about 40% of the state’s dentists accept Medi-Cal payments as it is, and Hanlon told me a CDA survey indicates that half would stop accepting Medi-Cal patients and many others will accept fewer patients.

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“It’s appalling that when the cost of providing healthcare is at an all-time high, the state is considering cutting program funding back to 1990s levels,” Hanlon said. “These cuts … will force patients to forgo or delay basic dental care, driving completely preventable emergencies into already overcrowded emergency departments.”

Somkene Okwuego, who as a child in South L.A. was occasionally a patient at USC’s Herman Ostrow School of Dentistry clinic, will graduate from the school in just a few months.

I first wrote about Okwuego three years ago, after she got an undergrad degree in gerontology, and she told me a few days ago that many of her dental patients are elderly and have Medi-Cal or no insurance at all. She has also worked at a Skid Row dental clinic, and plans after graduation to work at a clinic where dental care is free or discounted.

Okwuego said “fixing the smiles” of her patients is a privilege and boosts their self-image, which can help “when they’re trying to get jobs.” When I dropped by to see her Thursday, she was with 83-year-old patient Jimmy Stewart.

Stewart, an Army veteran, told me he had trouble getting dental care at the VA and had gone years without seeing a dentist before a friend recommended the Ostrow clinic. He said he’s had extractions and top-quality restorative care at USC, with the work covered by his Medi-Cal insurance.

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I told Stewart there could be some Medi-Cal cuts in the works this summer.

“I’d be screwed,” he said.

Him and a lot of other people.

steve.lopez@latimes.com

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Diablo Canyon clears last California permit hurdle to keep running

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Diablo Canyon clears last California permit hurdle to keep running

Central Coast Water authorities approved waste discharge permits for Diablo Canyon nuclear plant Thursday, making it nearly certain it will remain running through 2030, and potentially through 2045.

The Pacific Gas & Electric-owned plant was originally supposed to shut down in 2025, but lawmakers extended that deadline by five years in 2022, fearing power shortages if a plant that provides about 9 percent the state’s electricity were to shut off.

In December, Diablo Canyon received a key permit from the California Coastal Commission through an agreement that involved PG&E giving up about 12,000 acres of nearby land for conservation in exchange for the loss of marine life caused by the plant’s operations.

Today’s 6-0 vote by the Central Coast Regional Water Board approved PG&E’s plans to limit discharges of pollutants into the water and continue to run its “once-through cooling system.” The cooling technology flushes ocean water through the plant to absorb heat and discharges it, killing what the Coastal Commission estimated to be two billion fish each year.

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The board also granted the plant a certification under the Clean Water Act, the last state regulatory hurdle the facility needed to clear before the federal Nuclear Regulatory Commission (NRC) is allowed to renew its permit through 2045.

The new regional water board permit made several changes since the last one was issued in 1990. One was a first-time limit on the chemical tributyltin-10, a toxic, internationally-banned compound added to paint to prevent organisms from growing on ship hulls.

Additional changes stemmed from a 2025 Supreme Court ruling that said if pollutant permits like this one impose specific water quality requirements, they must also specify how to meet them.

The plant’s biggest water quality impact is the heated water it discharges into the ocean, and that part of the permit remains unchanged. Radioactive waste from the plant is regulated not by the state but by the NRC.

California state law only allows the plant to remain open to 2030, but some lawmakers and regulators have already expressed interest in another extension given growing electricity demand and the plant’s role in providing carbon-free power to the grid.

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Some board members raised concerns about granting a certification that would allow the NRC to reauthorize the plant’s permits through 2045.

“There’s every reason to think the California entities responsible for making the decision about continuing operation, namely the California [Independent System Operator] and the Energy Commission, all of them are sort of leaning toward continuing to operate this facility,” said boardmember Dominic Roques. “I’d like us to be consistent with state law at least, and imply that we are consistent with ending operation at five years.”

Other board members noted that regulators could revisit the permits in five years or sooner if state and federal laws changes, and the board ultimately approved the permit.

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