Dive Brief:
- Roche said Thursday it’s discontinuing two Ionis-partnered drugs for Huntington’s disease after clinical setbacks, with one missing its main trial goal and the other suspended because of a safety worry.
- A Phase 2 test of the antisense oligonucleotide tominersen “did not meet its efficacy objective” in spite of having a significant impact on biological disease signs, Roche said in a letter to patient groups. Meanwhile, enrollees in a Phase 1 trial of a drug codenamed RG6496 won’t receive a second dose because animal safety testing revealed that it “cannot be given chronically with repeated doses,” Roche said.
- The Swiss pharmaceutical giant had once before suspended a late-stage trial of tominersen because it didn’t appear to be helping patients. Roche forged ahead with a hypothesis that younger and less-advanced patients might benefit, but now that pathway has hit a dead end.
Dive Insight:
A genetic disorder, Huntington’s leads to the breakdown of nerves and a progressive inability to think, move and function. No treatment has so far been approved to slow the condition’s march, although some drugs can effectively control certain symptoms. UniQure has come the closest to gaining approval of a therapy that can change the trajectory of Huntington’s, although its progress has been slowed by an unusual controversy with the Food and Drug Administration.
Administered into the spinal fluid, tominersen suppresses production of a mutant form of the “huntingtin” protein that leads to Huntington’s. That biological action didn’t yield a benefit on disease progression, though, as the “Generation HD2” trial showed tominersen treatment didn’t produce a difference in enrollees’ scores on functional, cognitive or physical tests when compared to a placebo.
RG6496 was intended to be a more selective drug than tominersen that wouldn’t affect non-mutated huntingtin. But the Phase 1 “Point-HD” study had only given the drug to three patients before researchers detected a problem.
“While there is no safety concern for people to receive one dose, we have chosen to stop the Point-HD study early, because we can no longer offer participants the possibility of long-term treatment,” the letter stated.
Broadly, Roche said the two decisions were “independent, data-driven events, which have coincided by chance.”
“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,” the letter stated.
For Ionis, it’s a second significant blow in a day. The company and partner AstraZeneca also announced that a trial testing a drug called eplontersen against a rare cardiovascular condition had failed. Shares fell 24% on Thursday, to close at $64.27 apiece.
