Athira had clung to the hope that its experimental drug fosgonimeton could overcome a phase 2 failure in Alzheimer’s to demonstrate success in Parkinson’s and dementia. Unfortunately, a mid-stage trial in those indications has been no kinder.
The SHAPE trial had originally been designed to enroll 75 participants with Parkinson's disease dementia or dementia with Lewy bodies. However, Athira ended up cutting off enrolment at 28 subjects back in October 2022, citing “subsequently identified study design limitations” and the prioritization of resources toward its Alzheimer’s program.
The shrunken pool of participants was randomized to receive either a daily injection of 40 mg or 70 mg of fosgonimeton—a modulator of the hepatocyte growth factor (HGF) system—or placebo over 26 weeks. The primary endpoint was a combined score of cognitive assessment and working memory, for which fosgonimeton failed to beat placebo.
To try and find a positive, Athira had to shrink its scope to just five patients in the modified intent to treat (mITT) population who had received the 40 mg fosgonimeton dose, which it said had seen a “statistically significant” improvement in their cognitive score compared with seven patients who received placebo.
“Results for patients in the 70 mg treatment group were inconsistent, potentially due, in part, to a higher dropout rate (50%) from baseline enrollment than both the 40 mg (22%) and placebo (22%) groups,” the company said.
CEO Mark Litton, Ph.D., also tried to put a brave face on the results, which he branded “encouraging” as they “further bolster our confidence in the ongoing phase 2/3 LIFT-AD trial of fosgonimeton as a potential treatment for Alzheimer’s disease.”
Today’s findings support the company’s move in May to remove the 70 mg dose from that ongoing Alzheimer’s study and focus on 40 mg injections, Litton argued. The company is on track to complete enrollment in the LIFT-AD trial in early 2024 with a topline readout due in the second half of next year.
“More broadly, we are encouraged by the clinical and preclinical evidence that support the potential therapeutic effects of HGF system positive modulation across a wide range of neurodegenerative diseases,” the CEO added.
Even Athira’s Alzheimer’s ambitions are built on shaky ground, with fosgonimeton having failed a phase 2 trial in the neurodegenerative disease back in June 2022. Not to be deterred, Athira zeroed in on the 40% of participants who received fosgonimeton as a single agent, who it claimed experienced a “potentially beneficial” cognitive improvement and powered on into phase 3.
Investors didn’t seem overly concerned by today’s results. The biotech’s stock was trading down around 6% at $1.93 in premarket trading from a Monday closing price of $2.05.
Controversy has swirled around Athira in recent years, with the company’s work being overshadowed by an investigation into whether its then-CEO altered images, which led to her ousting in late 2021. It was followed by a push by an activist investor to shake up the biotech’s C-suite and board of directors.