Contributor: By lowering standards, the FDA is doing patients with rare diseases no favors

If you’re suffering from a serious illness, you better hope it’s not rare.

After the often difficult path to diagnosis, people with rare diseases likely have no good treatment options and none on the horizon. Many of these conditions are not well understood, and conducting studies in small patients is practically impossible. Most drugs won’t pan out, and those that do will have little demand and financial payoff, regardless of how useful they are. Pharmaceutical companies usually turn their attention elsewhere.

Recognizing these challenges, policymakers have worked since the 1980s to encourage drug development for rare diseases. They have established dedicated, dedicated federal research funding programs In Food and Drug Administration, extended Protection against competition To help secure benefits, and to promote benefits A rare pediatric disease. Yet, 95% of rare diseases, which affect an estimated 30 million Americans, lack of Any approved treatment.

some Blame the FDA. They say that the administration is very strict, imposing Impossible needs and requiring unequivocal proof of efficacy and safety for rare disease drugs. Some suggest that patients would be better off if the FDA were left alone Get out of the way – Not only for the treatment of rare diseases, but also widely.

The current administration seems determined to do so, at least for products that are suitable “Make America Healthy Again” agendasuch as stem cells and psychedelics (never mind the latter interventions cOVID Vaccinations and Abortion medicine).

A large portion of FDA experts DOGE has been done Or otherwise forced out Agency Commissioner Martin Macri has proposed to approve the drug on their basis Scientific justificationwhile the agency’s chief medical and scientific officer make a promise “Stepping on the first sign of promise for rare diseases” – potentially providing a cure much sooner, even though many drugs that initially look promising don’t work.

Just last month, the FDA announced approval The Narcotics Commissioner claimed that he would help “Hundreds of thousands of childrenWith autism, based not on clinical trials but on the basis of published case reports of 40 patients with a potentially related condition – dangerously and uniquely accepting myths as evidence of efficacy.

The FDA’s disarmament call comes from within.

It is necessary to criticize the lies of the administration not newbut critics are especially sound now. Banking on the expectation that the The Trump administration To break through familiar red tape, they’re calling on the White House and new FDA leadership to approve rare disease drugs. Too little attention to safety and efficacy in contrast To protect the financial interests of companies In developing and bringing to market treatments for rare diseases.

It may be appropriate to evaluate rare disease drugs differently as market-driven incentives often fail to obtain 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 drug it rejected just wasn’t good?

Ideally, you want to see the drug’s effectiveness repeated in at least two studies to have confidence in the results. For drugs approved to treat common diseases (outside of cancer), this duplication is common. but Only 13% approved rare Disease medicine (Then Beyond Cancer) relied on more than one strong clinical trial to show that they work. The latest FDA Policy It has been clarified Unit Study Method There will be rule for rare disease drugs and potential Other conditions Going forward

There are also drugs for rare diseases Increasingly given”Fast approvalAn approach that allows drugs for serious diseases to be approved based on predictability rather than proven benefit. Companies must complete the necessary studies after approval, but the FDA has allowed drugs to remain on the market even if those studies fail. Recent gene therapy For Duchenne muscular dystrophy, a treatment that was later linked Death of patients.

Even outside of accelerated approval, the agency sometimes approves drugs that miss pre-set targets for proving the drug works. A A recent study found that this occurred in 1 in 10 approvals, nearly half of which were for rare diseases.

Despite this moderation, criticism continues. Rather than treating the FDA’s refusal to approve a drug as an important warning sign, these decisions are often met with the assumption that the FDA Must be wrong.

Take the latest administration action on elamipretide for Barth syndromeA very rare, life-threatening genetic disorder characterized by abnormalities of the heart, muscles and immune system that affect 300 patients Internationally.

Given the small patient population, Stealth Biotherapeutics, the company that makes elamipretide, conducted a test in only 12 people, which failed to show the drug worked. Some patients continued in the extended version of the trial and appeared to perform better in the walking distance and fatigue tests. However, the FDA is reasonably concerned that this may be due to patients’ awareness that they are receiving the drug, leading to a placebo effect.

After reviewing the evidence, the FDA issued a the letter Declined to approve elamipretide in May 2025. Identification of the need flexibilityHowever, the agency left the door open for approval based on a new, unproven measure of patient benefit: muscle strength in the knee. In September, significant follow-up Public criticism from Patient advocates and members of Congressthe FDA granted fast-track approval of the drug. Stealth will now complete another study to see if the treatment actually helps patients — but even if that study fails, the agency may not withdraw approval.

Even if elamipretide fails to complete, one might wonder what harm there is in just approving it. Perhaps it could provide some hope to patients who have none, while encouraging companies to abandon rare diseases.

Here’s the problem: Those who criticize the FDA for setting the bar too high for trial data that fail to show benefit, argue that it This does not mean that the medicine is ineffective. But it is very difficult to prove that drugs no If that’s the norm, FDA reviewers should just shut up shop, leaving a universal “approved” stamp on any drug that doesn’t seem to kill patients.

When it works well, FDA approval tells patients (and their doctors and insurers) “this drug has been shown to work”—or at least “this drug has been shown to be likely to work.” If FDA approval means something less, such as “This drug is not indicated no To work,” it fails to serve patients, leaving them no better than searching Unproven dietary supplements on Amazon. They may be even worse, if relying on FDA approval as a meaningful indicator of benefit.

Patients with rare diseases, like all patients, must have drugs that work. The burden should be on the companies to prove that their drugs do. Changing or altering this burden by changing FDA approval criteria will not help, but other changes may. For example, policy makers can develop Existing legal procedures It allows patients with serious illnesses to try investigational drugs that have not yet been approved. The federal government could also increase support for the research needed to understand, diagnose, and treat rare diseases, helping companies focus on the most promising goals and helping reduce failures. Unfortunately, the Trump administration running Destruction Rather than federal health agencies and research, rare disease sets back the science.

Public trust in authorities like the FDA has already eroded. Demanding that the agency give the green light to more rare disease drugs, evidence undermined, will make the problem worse — and likely leave rare disease patients no better. Instead of blaming the FDA, policymakers, companies and patient advocates should do all they can to get better drugs before the agency’s reviewers.

Holly Fernandez Lynch is a senior partner in this field 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 collaborates in the Department of Medicine. Yale Collaboration for Regulatory Rigor, Integrity and Transparency.