Betting on biotech is always a gamble, David Wainer writes in Heard on the Street. But in the first year of this administration, few corners were dicier than rare-disease drugmakers — and the reason is worth understanding, because it is the whole trade.
What these companies are up against
Rare-disease drugmakers often test in tiny patient groups, sometimes without the usual features of large trials such as placebo controls. If a disease affects a few thousand people, a conventional randomized trial can be impractical or ethically fraught.
Under the second Trump administration, these companies suddenly faced Food and Drug Administration officials skeptical of approving drugs on such limited evidence. The shares plunged.
Now many of those officials are gone — FDA Chief Marty Makary resigned — and under acting Commissioner Kyle Diamantas the agency has walked back several high-profile decisions. Replimune’s (REPL) melanoma treatment was approved on its third attempt, a case that had become a flashpoint and drew White House involvement.
The result: uniQure (QURE) up 77.6% year to date, Replimune up 33.3%, the SPDR S&P Biotech ETF (XBI) up 26.4%.
The trade, stated honestly
Wainer’s framing is the most useful thing in the column, and it is admirably free of spin. In risky therapeutic areas, he writes, the cleanest part of the trade is often the run-up to approval, when the only question is whether the FDA says yes. Approval “de-risks” the drug from being an experiment.
But after that, new questions arrive. Will insurers pay for treatments that can cost millions of dollars? Will it prove safe and effective enough that patients take the risk? Which explains why Replimune soared on August approval and has since given some of it back.
uniQure sits right at that pre-approval moment. It is developing a one-time gene therapy for Huntington’s disease — infused into the brain through a hole in the skull — that aims to slow progression of a devastating neurodegenerative disorder. Its history is a case study in regulatory risk: positive data in late 2025 quadrupled the stock; then officials said the trial design their predecessors had accepted would no longer suffice, questioning results drawn from a historical database rather than a placebo group, and the stock cratered; then in June new leadership flipped again and agreed to let the company file.
The three-year data showed a high dose slowing progression 75% versus a historical comparison. Four-year data is expected by month-end. Joseph Thome of TD Cowen says the odds of accelerated approval are “skewing positive,” partly because the FDA has returned to its “old body language,” and notes that at roughly $3 billion of market value the company “still isn’t priced for success.” Huntington’s affects an estimated 40,000 Americans, with no approved treatment shown to slow it.
Why flexibility isn’t the same as a green light
Regenxbio (RGNX) is the cautionary case. In June the FDA reversed its rejection of the company’s gene therapy for a rare inherited disorder, clearing a resubmission and sending shares higher. In August the stock plunged after the agency placed the therapy on clinical hold when spinal scans turned up abnormalities in some trial participants.
Healthcare policy consultant Ipsita Smolinski frames what has actually changed: willingness to expedite drugs to desperate patients doesn’t mean standards have been lowered. It shows the FDA has grown “more willing to separate approval now from proven clinical benefit later.” The accelerated pathway still requires a confirmatory trial.
Wainer’s conclusion is the sentence to remember: the bet here isn’t that uniQure’s therapy works — that question might not be settled for years. The bet is that the FDA is once again willing to let patients, and investors, take that risk before all the evidence is in.
What a household should take from this
Mostly: recognize what kind of return this is. A stock that doubles because a regulator softened is carrying political risk dressed as scientific risk, and political risk reverses on a personnel change. uniQure’s own chart — quadruple, crater, double — is the same drug and the same data throughout.
That is a legitimate thing for a professional to underwrite with position sizing and a stomach for binary outcomes. It is a poor fit for money that has a job and a date attached to it, which describes most of what sits in a retirement account.