Another of Ionis Pharmaceuticals’ key midphase readouts has fallen short of expectations, prompting the biotech to stop studying the Roche-partnered candidate in an advanced form of age-related macular degeneration.
Roche exercised its option on the drug candidate, which is variously called IONIS-FB-LRx, RO7434656 and RG6299, in 2022. The Swiss drugmaker took responsibility for global development, with the exception of an open-label phase 2 IgA nephropathy (IgAN) trial and a phase 2 study in geographic atrophy (GA). In June, Ionis identified the GA readout as one of the key value-driving events planned for 2024.
The event failed to drive value. Rather, Ionis stopped development of the candidate in GA after seeing the results of the 332-patient phase 2 study that wrapped up in June. Ionis said it saw “favorable safety profiles and good target engagement, but insufficient efficacy to advance into phase 3 development.”
Roche is continuing to enroll patients in its phase 3 IgAN study, and data from the open-label trial in the chronic kidney disease remains on Ionis’ road map for the year. But Ionis no longer sees a future for the asset in GA.
Ionis’ interest in testing the drug in the eye disease reflected evidence that the alternative complement pathway is linked to GA. Overproduction of complementing factor B, an activating factor in the pathway, is associated with higher risk. Roche targeted similar biology with complement factor D-binding antibody fragment lampalizumab only to see the candidate fail a phase 3 clinical trial in GA in 2017.
Lampalizumab was administered into the eye. With most factor B produced in the liver, Ionis gave its GA drug candidate systemically to try to stop the accumulation of the complement factor and the resulting destruction of the macula. Ionis CEO Brett Monia, Ph.D., acknowledged that rationale may fail to translate into an effective drug at a TD Cowen investor event in June.
“It's a significantly risky program. But on the other hand, the upside is enormous, since this drug would not have to be intravitreally administered, it would be injected using a simple auto-injector once per month by the patient themselves,” Monia said. “It could be a real breakthrough, game changer for this indication, but it does not come without risk.”
Ionis disclosed the failure of IONIS-FB-LRx to live up to that billing alongside confirmation that ION541 is no longer part of its plans. The biotech and partner Biogen reported the termination of development of the amyotrophic lateral sclerosis candidate, which is also called BIIB105, in May after seeing phase 1/2 data.