Roche calls it quits on Phase III study of Huntington's disease drug tominersen

Roche on Monday said it has stopped dosing patients in the Phase III GENERATION HD1 trial testing the antisense oligonucleotide tominersen as a potential treatment for manifest Huntington's disease. The decision follows a pre-planned review from the study's independent data monitoring committee, which based its recommendation on the investigational drug's potential benefit/risk profile, although Roche pointed out that "no new or emerging safety signals" were identified in the review.

"This is very unfortunate news to deliver on the tominersen Phase III study," remarked Levi Garraway, head of global product development at Roche. "GENERATION HD1 is the largest clinical trial in Huntington's disease to date and we do know that the data generated will significantly advance our understanding of huntingtin (HTT)-lowering as a potential treatment approach," he added.

Tominersen was previously granted orphan drug and PRIME designations by the FDA and European Medicines Agency, respectively. Roche licensed the drug, also known as RG6042 or IONIS-HTTRx, from Ionis Pharmaceuticals for $45 million in 2017. The antisense therapy is designed to reduce the production of all forms of HTT, including its mutated variant mHTT. Roche launched the GENERATION HD1 trial in 2018 after positive data from a Phase I/II study had demonstrated correlations between reductions in mHTT and improvements in clinical measures of Huntington's disease.

Phase III readout was expected in 2022

Roche did not specify what precisely led it to abandon GENERATION HD1, although drug division head Bill Anderson hinted this past February that the company was expecting the trial to run a little longer, saying there would be no "game-changing data" for tominersen until 2022. Aside from dropping the Phase III trial, Roche stated Monday that dosing has also been "paused" in the GEN-EXTEND open-label extension as the company works out next steps. The Phase I GEN-PEAK study of tominersen and the observational Roche HD Natural History Study will continue.

Roche is also pursuing a potential treatment in Huntington's disease via its Spark Therapeutics gene therapy unit that it acquired in 2019. Meanwhile, Novartis has said it also plans to test its drug branaplam as a potential treatment for Huntington's disease. The oral RNA splicing modulator, also known as LMI070, is currently under investigation for spinal muscular atrophy (SMA) and has shown the ability to reduce huntingtin mRNA in SMA patients, according to the company. The FDA recently designated branaplam an orphan drug, with Novartis saying it planned to start a Phase IIb trial in Huntington's disease patients this year.

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