- Roche has stopped dosing in a Phase 3 trial of Ionis Pharmaceutical's Huntington's disease drug tominersen, stating Monday that a data monitoring committee recommended the suspension "based on the investigational therapy’s potential benefit/risk profile." The panel did not see any new or emerging safety signals, Roche said.
- In a call with Wall Street analysts, Ionis executives said they hadn't seen the data that was reviewed by the committee. However, they added that the decision wasn't based on a "futility" analysis, which is used to judge whether an experimental drug helps study participants.
- Ionis executives said they don't believe the setback is an indication that the company's other nervous system-targeting drugs would also struggle in clinical trials. Still, shares in the company tumbled 19% Tuesday morning. The update also reverberated through three other companies working in Huntington's — Wave Life Sciences, UniQure and PTC Therapeutics — which each saw their shares drop as well.
Huntington's disease, a progressive neurodegenerative disorder, is caused by a dysfunctional form of a protein called huntingtin that is stimulated by mutated DNA. Ionis and Roche are trying to fight the disease by blocking that section of DNA with a piece of genetic material that effectively stops the production of both mutated and normal huntingtin.
This technology has been successfully used in Ionis-discovered drugs like Spinraza, a spinal muscular atrophy treatment marketed by Biogen, as well as Waylivra and Tegsedi, which both target rare, inherited conditions.
Without data, neither Roche nor Ionis could comment on the specific reasons the data monitoring committee recommended the suspension. The decision affects a late-stage, placebo-controlled study that enrolled over 900 patients and aimed to test whether tominersen slowed disease progression. It also affects an open-label extension study that enrolled patients from all trials of the drug.
A Phase 1 dosing trial will continue, the companies said.
Ionis executives said the decision was disappointing. But until the data has been fully analyzed by Roche, the suspension "does not mean the program has died," according to CEO Brett Monia.
Among the factors that researchers may want to review is whether blocking normal huntingtin protein affects patients, and whether tominersen's administration method — via an injection in the spinal column — fails to deliver enough drug into brain tissue where Huntington's disease is most damaging. Spinraza, the Ionis drug marketed by Biogen, also uses a spinal injection, but the disease it treats, spinal muscular atrophy, affects tissue more immediate to the spine.
While Ionis is optimistic, some Wall Street analysts believe Monday's update signals an eventual discontinuation of tominersen research. "We think this is likely the end of the road for tominersen," RBC Capital Markets analyst Luca Issi wrote in a March 22 note to clients.
Ionis' remaining nervous system drugs, such as the Biogen-partnered ALS drug tofersen, might perform better. Stifel analyst Paul Matteis described ALS as a disease more like SMA in its ability to be altered by a drug injected into the spine, for example.
At the same time, other companies working in Huntington's disease may not run into the same problems as Ionis and Roche. Mizuho analyst Salim Syed noted, for example, how Wave's drug, which uses a similar technology to Ionis, targets more of the mutant huntingtin.
UniQure, meanwhile, uses a gene therapy designed to silence mutant huntingtin that is delivered via catheter into the affected brain tissues, Matteis wrote.