Dive Brief:

• Shares of UniQure dipped more than 10% Tuesday morning after the biotechnology company released more data from a small study testing an experimental gene therapy for Huntington’s disease.
• The new results include up to 30 months of follow-up from 39 patients enrolled in the study, which is evaluating two doses of UniQure’s therapy, called AMT-130. The company said there’s evidence both doses are generally safe and can preserve or improve neurological function in patients with the disease, which progressively impairs movement and cognition.
• While UniQure leadership describes the results seen so far as “very promising,” analysts on Wall Street have found them puzzling. The low dose, for example, has appeared more effective and less variable than the high dose. How long either stays effective is also unclear. Nevertheless, UniQure intends to engage with regulators early next year to talk through the data it’s collected and “potential strategies for ongoing development of AMT-130.”

Dive Insight:

Huntington’s is caused by mutations in the gene responsible for making the similarly named “huntingtin” protein. While helpful to brain function in its normal form, the protein, when mutated, bunches together into toxic clumps that damage nerve cells.

AMT-130 is designed to silence that malfunctioning gene, and has become one of UniQure’s most closely watched programs.

In its update, UniQure said neurological function in patients given the high dose of AMT-130 was preserved or improved 18 months after treatment, compared to the start of the study. That was measured by a scoring system known in short as cUHDRS, which assesses the motor function, brain function and behavior of people with Hungtinton’s.

In the low dose arm, two other scales found neurological function was preserved at 30 months, according to UniQure.

The company added that, across all three measurements, AMT-130 showed “favorable trends” on the expected rate of decline compared to a natural history cohort. The cohort, which UniQure created with assistance from a nonprofit research organization, includes 31 patients with early Huntington’s disease who were similar to the participants in the AMT-130 study. Drugmakers use natural history data to better understand how a disease progresses without intervention.

Given the design of AMT-130, the study has been measuring the amount of mutant huntingtin present in the fluid surrounding the brain and spine.

There, average changes “continue to be variable,” according to UniQure, which claims that, because AMT-130 is administered deep in the brain, such measurements “are not believed to be materially representative” of mutant huntingtin levels in targeted brain regions. The company previously disclosed that mutant huntingtin levels varied across the studied two doses. In the low dose arm, they had declined an average of 8% two years after treatment, while in the high dose arm, they had increased an average of 40% one year after treatment.

UniQure’s study has also been charting levels of “neurofilament light chain,” a molecule that research suggests is indicative of brain and nervous system damage. It has become an increasingly important measure for drugmakers trying to prove their therapies can protect nerve cells. UniQure said Tuesday that, 30 months after treatment, average levels of the molecule had declined 6.6%. And for the high dose arm, they were “near baseline” at month 18.

UniQure said there have been four serious adverse events in the high dose arm that were deemed related to AMT-160. Three were central nervous system inflammation and one was severe headache later also attributed to central nervous system inflammation.

UniQure said patients with symptoms of this inflammation improved after receiving glucocorticoid medication. Six patients in the high-dose arm received perioperative steroids when they got AMT-130 to reduce the risk of inflammation.

UniQure shares were trading below $7 apiece late Tuesday morning.