Investors keenly awaiting one-year safety data from uniQure’s Huntington’s disease gene therapy have rewarded the company with a 20% share bump, as the data showed a clear safety profile.
There’s still plenty to learn about AMT-130—for instance, the company has not yet reported efficacy data. But the 12-month update from the low-dose group of the phase 1/2 trial showed that the therapy was well-tolerated, with no significant safety issues and there was a reduction of a key biomarker. The data comes from just 10 patients with early Huntington’s disease, of which six received AMT-130 through a surgical procedure and four received a sham procedure.
On the biomarker, uniQure reported a 53.8% reduction in mutant huntingtin protein (mHTT), which disrupts cellular processes and leads to neurodegeneration in the evaluable patients.
There were two serious adverse events in the trial that were deemed unrelated to treatment with AMT-130. One patient experienced deep-vein thrombosis in the elbow and another had post-operative delirium that resolved with supportive care. MRI testing did not reveal any clinically meaningful safety findings, the company said.
UniQure also tracked a biomarker that signals neuronal damage called CSF NfL, finding that measurements increased as expected after the surgical procedures and then approached baseline at 12 months. In the six treated patients, the increase in CSF NfL peaked one month after the surgical procedure and had declined at 12 months, but sat at an 8% increase compared to baseline.
The four control patients had stable or slightly declined CSF NfL over 12 months.
So what does this all mean? Investors were anticipating this data, according to Mizuho analysts, who said in a preview note earlier this month that data from four patients released in December 2021 had disappointed. Mizuho predicted that the biomarker data this time around would be “noisy and variable” since the enrolled patients are pre-symptomatic, the sample size is small and the data is coming from the low-dose group.
But investors clearly saw something they liked in the data, which Mizuho said were indeed “noisy" in an update. UniQure’s shares jumped to $18.13 Thursday morning from a market close of $15.39.
Mizuho noted significant variability between the patients, but the mHTT reductions were unexpected—and significant. This bodes well for the high dose readout, expected next year.
"Whether this mHTT reduction will translate to clinical improvement is still a question that will likely be answered in 2Q23 when uniQure will share clinical data from the low- and high-dose cohorts," Mizuho wrote.
UniQure has much more to prove with this gene therapy approach to Huntington’s disease, a devastating degenerative brain disorder caused by a defective gene that leads to the progressive breakdown of nerve cells in the brain. The U.S.-based phase 1/2 trial has 26 patients total enrolled, with the remaining 16 patients in the high dose group.
Additional data from the trial will be released next year, according to uniQure’s president of research and development, Ricardo Dolmetsch, Ph.D.
Another European trial is ongoing with six patients enrolled in an open-label study with a low dose. The company is also enrolling a high dose cohort there as well.
Safety is key when it comes to early data readouts for gene therapies. Companies large and small have been plagued by various safety issues as they move these cutting-edge treatments through the clinic. Even uniQure is familiar, as its hemophilia B gene therapy was put on clinical hold by the FDA in December 2020 on concerns about a case of liver cancer that was potentially related to the treatment. The trial was eventually allowed to continue after an investigation determined the gene therapy was “highly unlikely” to have been the cause of the cancer.
Editor's note: This story was updated at 12:05 p.m. ET on June 6, 2022, to include analyst commentary.