Roche has halted development on two of its Huntington’s disease prospects, delivering another blow to a patient community that has long awaited new medicines.
The Swiss drugmaker explained its reasoning in a July 9 letter to the patient community.
The canceled studies are the phase 2 trial of Ionis-partnered tominersen and the phase 1 trial of RG6496.
“We have made the difficult decision to discontinue both clinical development programmes,” Mai-Lise Nguyen, patient partnership leader at Roche, wrote in the letter. The tominersen trial did not meet its efficacy objective, while RG6496’s study was stopped based on results from a separate animal study.
“These are independent, data-driven events, which have coincided by chance,” Nguyen wrote. “While this news is deeply disappointing, promptly communicating about the findings is the most responsible way for us to honor the contribution of study participants and allow the HD community to focus efforts on other avenues of research.”
Both drug candidates are antisense oligonucleotides targeting the huntingtin gene, which causes Huntington’s disease when a mutation leads to its steady expansion over time.
The tominersen trial met its safety and biomarker endpoints, according to the letter, but the reduction in mutant protein observed in patients on the drug didn’t come with a concurrent improvement in disease severity at the end of the 16-month treatment period. RG6496’s trial, meanwhile, had enrolled three patients when an animal study revealed that the drug “cannot be given chronically with repeated doses,” prompting Roche to end the first-in-human test.
Regarding next steps, Roche told the Huntington's community that it will focus on supporting trial participants and helping ease their transition, with the company pledging to present the data in the future after continued analysis.
The company clarified that its phase 1/2 trial of its Huntington's disease gene therapy candidate RG6662 remains "ongoing as planned."
Tominersen has a long and rocky history. Roche exercised an option to license the molecule from Ionis back in 2017, but the candidate since flopped in a phase 3 trial, prompting a rollback to earlier development stages and denting the drug’s blockbuster expectations.
The phase 2 trial that Roche built from the phase 3 wreckage, known as GENERATION HD2, has now become the latest failure for the once-promising tominersen.
Ionis shares “Roche’s deep disappointment in today’s announcement regarding the discontinuation of the Phase 2 GENERATION HD2 study of tominersen,” a spokesperson told Fierce.
“Ionis remains focused on advancing our neurology pipeline and bringing new medicines to people living with serious conditions,” the spokesperson continued. “This includes zilganersen, which is under FDA review as the potential first and only treatment for Alexander disease.”
Huntington’s disease has long vexed biotech, with no medicines currently approved that target its underlying biology.
A gene therapy from Dutch biotech uniQure could become the first approved disease-modifying Huntington’s treatment. The company plans to file the therapy, AMT-130, in the third quarter of this year, following a shocking reversal from the FDA.