In order to copeHuntingtonchronic diseases,RocheAs early as 2017, a patent licensing agreement was signed with Ionis for a novel antonym therapy for proteins related to Huntington's disease. Now, after experiencing early safety warnings, Roche announced the cessation of a phase III clinical study under the order of the Data Commission.
Roche said the company had stopped administering tominersen's phase III clinical study of the antonym drug huntington protein and mutants after the independent data committee “made recommendations on the potential benefits and risk profile of study participants based on survey therapies.”
Roche obtained permission from Tominersen (formerly Ionis-HTTRX) in 2017 and paid Ionis Pharmaceuticals a license fee of 45 million US dollars. Before discontinuing administration, Roche had recruited 791 patients in 18 countries to participate in the Phase III clinical study of GENERATION HD1. This double-blind, placebo-controlled study performed tominersen tests on patients with Huntington's disease for 25 months and randomly divided into taking 120 mg of medication every 2 months and taking 120 mg of medication or placebo every 4 months.
Roche also stopped an open label extension study called GEN-EXTEND, which used the same high-dose and low-dose regimens. The company said it will further update the drug's plans after further evaluation of the data and plans to continue monitoring patients' safety signals through the study's trial window.
Roche pointed out that the committee's decision did not involve new security risks. This will dispel some of the concerns and allow it to continue into later stages of testing in another phase I clinical study. In March of last year, Roche suspended the study, called GEN-PEAK, because researchers discovered two cases of intrathecal catheter-related infections unrelated to the drug. The study has since continued, and Roche said there are currently no plans to stop it.
Tominersen is an anti-translational nucleic acid drug. When combined with Huntington's mRNA, it degrades this mRNA through an RNA degradation system, thereby reducing the expression of toxic proteins, which may alter the course of the disease. In a phase I/II clinical trial, this drug significantly reduced the level of mutated Huntington protein in spinal fluid, but today's trial showed that this change did not translate into curative effect. Since there don't appear to be any emerging safety issues, the flaw is probably that the efficacy is not obvious. Similar to Spinraza, another major ASO and SMA drug discovered by Ionis, Tominersen also requires spinal administration.
