uniQure pauses part of Huntington's trial after 3 patients hospitalized—1 of whom hasn’t fully recovered

Three patients treated with the higher dose of uniQure's Huntington's disease gene therapy have been hospitalized, including one who has yet to fully recover.

UniQure disclosed the serious side effects Monday in a second-quarter earnings report, saying the cases were relayed to health authorities in July. The three cases were among 14 patients treated with the higher dose of AMT-130 in a phase 1/2 trial. 

The three hospitalized patients had a mix of symptoms but all experienced either nausea or vomiting. The first patient—enrolled in one of the study’s EU sites—was hospitalized with “fever, vomiting, mania and involuntary limb movements” according to a statement from a UniQure spokesperson. An MRI found swelling on a part of the brain where the treatment is administered. The patient was treated with steroids but has yet to fully recover and continues to have “some subtle deficits in verbal fluency and attention relative to the pre-operative state.”

An additional patient in the EU was diagnosed with eye swelling related to brain pressure and elevated cerebrospinal fluid pressure after similarly reporting vomiting and other symptoms when hospitalized. After receiving a lumbar puncture and medication, that patient has fully recovered. 

The final case was in the U.S. and was reclassified as an adverse event after a patient was hospitalized twice in a week due to severe headaches. After the second admittance, it was determined that a cerebrospinal fluid leak occurred due to the lumbar puncture required as part of the trial and the patient was treated with blood patches. The patient fully recovered but an MRI showed pressure in the part of the brain where the treatment was administered.

UniQure teased one-year safety data of a lower dose of the gene therapy in June. The early look found no safety issues with AMT-130 among an initial group of 10 patients, six of which were treated with the low dose. Fast forward more than six weeks and the same can't be said about the higher dose arm. 

As expected, the company is delaying further testing of the high dose while investigating the cause of the side effects, which is expected to take until next quarter. The trial’s data safety and monitoring board has yet to rule that the side effects are dose-limiting toxicities, meaning all eyes are on a report due in the fourth quarter.

CEO Matt Kapusta hypothesized on Monday's earnings call that the issue is not related to the drug’s mechanism of action but rather “something related to either the immune response or an inflammation associated with the product, or the procedure itself.” 

UniQure doesn’t expect these cases to impact low-dose procedures in the ongoing phase 1/2 trial or timing of the 2023 data readouts, saying the profile of the former remains strong.

The company's shares dropped 32.5% from $25.54 apiece to $17.25 as of Monday morning after the trial news and earnings report. 

AMT-130 is administered directly to the striatum region of the brain with three different infusions that ultimately spread to the rest of the brain, with the goal of lowering the production of the huntingtin protein. In addition to the safety data reported in June, the company found a 53.8% reduction in mutant huntingtin protein, a known biomarker for the disease.

AMT-130 is the second asset in the company’s pipeline behind the registrational-stage hemophilia B treatment AMT-061. The latter is currently under priority review at the FDA as was originally the case in Europe; however, uniQure also announced today that the review has switched to a standard procedure due to a “bandwidth issue” for regulators at the European Medicines Agency.