Coverage Surrounding FDA Head Is Missing Critical Fact

When my one-month-old daughter was diagnosed with biliary atresia — a rare disease that for most of human history was 100% fatal — I entered a world where hope and terror coexist.

Thanks to pioneers who pushed the envelope when everyone else had given up, at thirteen months old she underwent a liver transplant in Pittsburgh, and today she is alive and thriving in college.

So I understand intimately why families facing devastating illnesses want access to innovative therapies. But innovation only works if the science ecosystem can differentiate true innovation from failure.

A recent Wall Street Journal column argues that the U.S. Food and Drug Administration (FDA) is standing in the way of hope for rare disease patients. It frames the debate as a simple moral choice: let patients try promising therapies or deny them a chance at survival.

That framing is dangerously incomplete.

Most reasonable people agree that rare disease patients should have the right to try innovative therapies, provided the data are strong and the risks understood. But today, that right can be hijacked by investors with a financial stake in characterizing treatments as safe and effective on the basis of partial data. When investors sell false hope, patients lose the impartial referee they need.

Consider the gene therapy AMT-130, currently under development to treat the rare, neurodegenerative Huntington’s disease. Much-cited early data released by the sponsoring company suggests this treatment may slow Huntington’s progression by 75%. That claim has understandably sparked excitement, but the claim has serious problems.

The 75% improvement is based on a comparison to the progression of disease in external matched controls — patients pulled from a natural history database who never set foot in the trial. Such comparisons rest on the always shaky assumption that matched controls actually were similar to the active therapy group.

But the company’s own randomized sham trial gives us a way to check that assumption, and the check fails — the historical control group’s progression of disease looks nothing like the sham arm over the first year. The headline 75% number is built on a comparator the company’s own data contradicts. At best, these are hypothesis-generating findings that need to be confirmed in better trials, not data that should form the basis for an FDA approval, which ordinarily signals a strong likelihood of efficacy.

The Journal column correctly points out that a traditional placebo-controlled design would require sham brain surgery, where control patients undergo a procedure without receiving the therapy. The column frames this as unethical, but that framing is incomplete.

The FDA does not demand a sham for every procedure. It released specific guidance recommending sham procedures in neurodegenerative disease because the natural history of these illnesses is highly variable. You simply can’t tell whether a patient who stabilized would have stabilized anyway. A concurrent randomized control, in which the patient genuinely doesn’t know whether she received the therapy, absorbs that variability. An external historical control doesn’t.

The Journal also leaves readers with the impression that the FDA is demanding sham “brain surgery.” This is also not accurate. The actual sham procedure in the initial trial that showed no benefit involved small partial-thickness burr holes drilled under general anesthesia. This is far from a trivial procedure, but vastly less invasive than the full delivery of therapy into the brain, which requires hours of MRI-guided delivery of a viral vector deep into the brain. The FDA’s guidance explicitly calls for sham procedures to be as minimally invasive as possible. The agency is not asking for sham brain surgery; it is asking for the smallest procedure that can tell us whether the therapy works.

I remember grabbing onto any glimmer of hope in the year my daughter was dying from liver disease, so I understand the desperation of Huntington’s patients. But the FDA’s role is to present a non-distorted benefit and risk analysis, and to ensure no entity can exploit desperate, vulnerable patients. In a space where investors have every incentive to amplify data that makes a treatment look safe, the FDA has to demand rigor.

The normal scientific process — peer review, replication, confirming exploratory findings — appears to boosters as obstruction. But speed must be balanced against the FDA’s charge to deliver transparent, rigorous, unbiased evaluations.

The FDA is the only entity in this ecosystem explicitly tasked with standing between vulnerable patients and the powerful incentives of capital and marketing. A system without that safeguard would not yield better cures; it would result in patients seriously harmed by therapies that had no hope of working.

Dr. Anish Koka is an internist and cardiologist in Philadelphia, Pennsylvania.

The views and opinions expressed in this commentary are those of the author and do not reflect the official position of the Daily Caller News Foundation.