Tominersen for Huntington’s disease
Fact-checked by Joana Carvalho, PhDWhat is tominersen for Huntington’s disease?
Tominersen, previously known as IONIS-HTTRx and RG6042, was an experimental therapy designed to slow or prevent the progression of Huntington’s disease. It was originally developed by Ionis Pharmaceuticals and later developed in collaboration with Roche, which then acquired worldwide development and commercialization rights to the injection therapy. Development was discontinued in July 2026, however, due to a lack of effectiveness in clinical testing.
A rare genetic disease, Huntington’s is caused by a mutation in the HTT gene that leads to the production of an abnormal form of the huntingtin protein, which is key to the long-term survival of nerve cells in the brain. The abnormal protein tends to form toxic clumps inside nerve cells, which is believed to drive neurodegeneration in people with Huntington’s. That ultimately leads to a wide range of disease symptoms, including motor problems, cognitive impairment, and behavioral changes.
Tominersen was designed to bind to the HTT gene’s messenger RNA (mRNA), an intermediary molecule derived from DNA that contains instructions for cells to produce the huntingtin protein, and mark it for destruction. By doing so, tominersen was expected to reduce the production of both normal and abnormal huntingtin protein.
The therapy was administered by an injection directly into the spinal canal, known as an intrathecal injection, being delivered to the fluid surrounding the brain and spinal cord.
Data from a Phase 2 clinical trial showed that tominersen reduced levels of mutant huntingtin protein. However, the therapy failed to have any meaningful impact in terms of clinical effectiveness when compared with a placebo. Those findings led Roche to discontinue development of the treatment.
Therapy snapshot
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| Treatment name | Tominersen |
| Administration | Intrathecal injection |
| Clinical testing | Reached Phase 3 testing, but was discontinued in 2026 after failing to show clinical benefit in a Phase 2 trial |
Tominersen in Huntington’s clinical trials
Tominersen was tested in a series of clinical trials involving people with Huntington’s:
- An initial Phase 1/2a trial (NCT02519036), launched in 2015, enrolled 46 adults with early Huntington’s. Those results showed tominersen reduced mutant huntingtin levels and was tolerated well by participants.
- A following Phase 3 clinical trial, called GENERATION HD1 (NCT03761849), involved about 800 adults with Huntington’s who were randomly assigned to receive tominersen either once every two months or once every four months, or a placebo. Tominersen dosing was stopped in the study after an independent review determined that the therapy’s benefits did not outweigh its risks. The results indicated no clinical benefit of tominersen when administered every four months relative to a placebo. More frequent dosing was associated with worse clinical outcomes and side effects.
- A Phase 2 clinical trial called GENERATION HD2 (NCT05686551) was carried out to test lower and less frequent doses of tominersen in 301 people with early Huntington’s disease. The results, announced in July 2026, showed that while tominersen lowered the levels of mutant huntingtin protein and those of a marker of nerve cell damage, it did not have any meaningful impact in terms of clinical efficacy when compared with a placebo.
Following the results of the GENERATION HD2 study, Roche discontinued the therapy’s development.
Tominersen was found to be generally safe and well tolerated across studies. Commonly reported side effects were falls, headache, dizziness, common cold symptoms, and complications related to injections.
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