UniQure lost about a billion dollars in market value Tuesday after disclosing more data from the key clinical trial supporting the potential approval of its gene therapy for Huntington’s disease.
The four-year data come from a dozen participants who received a high dose of “AMT-130,” which is a one-time treatment designed to gum up production of the central protein that causes Huntington’s. Based on a scale assessing cognition, motor skills and daily living, UniQure said these participants showed a 44% slowing of disease progression compared to an updated external patient database that’s been serving as a control arm.
However, that difference wasn’t enough to reach statistical significance. A separate scoring system specifically focused on managing daily activities showed a 61% slowing of progression compared to the updated external control, which UniQure described as a “favorable treatment difference.” In a statement, the Netherlands-based company said the collective results demonstrate that AMT-130 continues to have a “meaningful” effect on disease.
But shareholders weren’t as convinced. UniQure’s stock price fell 40%, to trade just below $24, when the market opened Tuesday morning.
Analysts at Leerink Partners suspect investors will be concerned about how long AMT-130’s effects last. That’s because, alongside the four-year data, UniQure provided three-year data from 15 patients on the high dose. And there, scores looked stronger across those two scales. They respectively showed an 80% and 67% slowing of disease progression compared to the external control.
Importantly, though, there are “several layers” to UniQure’s release that “are critical to how we should interpret the data,” according to the Leerink analysts. One is the natural history database, which presents some challenges. Not only does the database get updated, which can alter results, but more information can go missing the longer patients are followed.
With a nerve-destroying disease like Huntington’s, patients often find it difficult to stay enrolled in an observational study as their symptoms progress. UniQure noted how, when looking at 48-month reference data from the updated, 53% of that information was missing. The treatment effect of AMT-130 at the four-year mark was therefore “likely understated,” UniQure said. Conducting an after-the-fact analysis, the company found disease progression slowed 54% and 68% on those two scales — which are known, in short, as the cUHDRS and the TFC.
“We recognize all the caveats this data update should come with and agree with them,” the Leerink analysts wrote in a note to clients. Still, Huntington’s is a devastating disease, “and slowing of any kind, especially on TFC which has remained stable ... is absolutely unheard of.”
“AMT-130 is clearly doing something,” they added. “Making patients wait for a better-conducted Phase 3 trial or other options just seems inappropriate to us when rare disease communities are willing to take on a greater degree of risk in exchange for time and an option.”
To Stifel analyst Paul Matteis, UniQure’s four-year results are “still impressive generally,” even if they represent “some regression,” whereas the fresh three-year results “look robust” and “are arguably most important, since this data cut is the crux” of the company’s alignment with the Food and Drug Administration.
“[T]he big picture here continues to support” accelerated approval, Matteis wrote in his own note.
Following a lengthy and highly unusual back and forth with the FDA, UniQure submitted an approval application late this summer. The company requested a certain kind of rapid review, which could lead to a verdict from the agency in about eight months.
In June, Leerink analysts estimated that, if approved, AMT-130 would be priced at $1.7 million in the U.S. and reach $2.5 billion in worldwide sales in 2030. Over the first six months of this year, UniQure recorded $9.4 million in revenue and a net loss of almost $135 million.
