Athira Pharma, Inc. (NASDAQ: ATHA), a late
clinical-stage biopharmaceutical company focused on developing
small molecules to restore neuronal health and slow
neurodegeneration, today announced topline results from its Phase
2/3 LIFT-AD clinical trial of fosgonimeton, a hepatocyte growth
factor (HGF) positive modulator, in patients with mild-to-moderate
Alzheimer’s disease (AD).
The topline results showed that neither the trial's primary
endpoint (the Global Statistical Test (GST), a combination of
results from measures of cognition (ADAS-Cog11) and function
(ADCS-ADL23)) nor its key secondary endpoints of ADAS-Cog11 and
ADCS-ADL23 reached statistical significance compared with placebo
at 26 weeks. However, both components of GST, cognition
(ADAS-Cog11) and function (ADCS-ADL23), directionally favored
fosgonimeton treatment, and in pre-specified subgroups
characterized by more rapid disease progression (moderate AD and
APOE4 carriers), cognition and function improved or stabilized in
the fosgonimeton treated group. In addition, data across biomarkers
of protein pathology (Aβ42/40, p-Tau181, and p-Tau217),
inflammation (GFAP) and neurodegeneration (NfL) showed directional
improvements with fosgonimeton treatment that are consistent with
the broad neuroprotective mechanism of HGF modulation.
“These are not the results we hoped for, as the lack of clinical
decline in the placebo group, combined with the short duration of
the study, may have impacted the trial’s ability to translate the
effect of fosgonimeton treatment into meaningful clinical
benefit,” said Javier San Martin, M.D., Chief Medical Officer of
Athira. “However, we believe the totality of the data
continues to suggest that positive modulation of the HGF pathway
has the potential to translate into improvement in parameters of
neuronal health and may mitigate disease progression.”
“While the trial did not meet its primary endpoint, the
biomarker and subgroup data are intriguing and remarkably
consistent not only across endpoints but also with our
understanding of fosgonimeton’s neuroprotective mechanism of
action,” added Anton P. Porsteinsson, M.D., Director of the
University of Rochester Alzheimer’s Disease Care, Research, and
Education Program (AD-CARE) and a LIFT-AD investigator.
Phase 2/3 LIFT-AD Clinical Trial Design and Topline
Results
LIFT-AD (NCT04488419) was a randomized, placebo-controlled,
double-blind study that evaluated the efficacy and safety of
once-daily subcutaneous injections of fosgonimeton (40 mg) in 312
mild-to-moderate AD patients not on acetylcholinesterase inhibitors
(AChEIs) compared to placebo over a 26-week treatment period. The
primary endpoint of LIFT-AD was the change from baseline after 26
weeks of treatment using the Global Statistical Test (GST), a
combination of results from measures of cognition (ADAS-Cog11)
and function (ADCS-ADL23). Secondary endpoints included cognition
(ADAS-Cog11), function (ADCS-ADL23), and a plasma biomarker of
neurodegeneration, neurofilament light chain (NfL). The trial
explored additional plasma biomarkers including glial fibrillary
acidic protein (GFAP), a marker of neuroinflammation, and both
amyloid beta and phosphorylated tau (pTau), hallmark measures of AD
pathology.
Primary Analysis PopulationTopline results from the LIFT-AD
study of fosgonimeton in mild-to-moderate AD patients after 26
weeks showed:
- A -0.08 change in GST favoring fosgonimeton that did not reach
statistical significance (p=0.70)
- The change in cognition from baseline as assessed by
ADAS-Cog11, for which a decrease from baseline represents
improvement, was -0.39 for the placebo group and -1.09 for the
fosgonimeton treated group, a difference of -0.70 (p=0.35) favoring
fosgonimeton
- In the fosgonimeton treated group, there was an increase
(improvement) of 0.65 in function as measured by ADCS-ADL23 versus
a decline of -0.02 in placebo, although this difference did not
meet statistical significance (p=0.61)
Prespecified Biomarker Analyses Data from the plasma biomarkers
of neurodegeneration (NfL), inflammation (GFAP), and protein
pathology (p-Tau181, p-Tau217, and amyloid beta 42/40 ratio) showed
consistent directional improvements favoring fosgonimeton versus
placebo after 26 weeks. Notably, fosgonimeton treatment reduced
plasma levels of pTau217, a hallmark of AD, by -0.12 pg/mL compared
to placebo (p<0.01).
Prespecified Subgroup Analyses In a prespecified subgroup
analyses of more advanced AD patients, a greater numerical
treatment effect in clinical outcomes was observed in the
fosgonimeton treatment group compared to placebo after 26
weeks:
- The change in cognition from baseline as assessed by ADAS-Cog11
in moderate AD patients, for which a decrease from baseline
represents improvement, showed the fosgonimeton treatment group
(n=61) improved compared to placebo (n=70), with a delta of -1.16
(p=0.39)
- For AD patients who are carriers of the APOE4 gene, the placebo
group (n=74) declined in cognition as assessed by ADAS-Cog11 over
the 26-week period as expected, whereas the fosgonimeton treatment
group (n=74) remained stable, with a delta of -1.07 (p=0.33)
Post Hoc Subgroup Analyses In a post hoc analyses by disease
severity as defined by baseline ADAS-Cog11 (>30) and Clinical
Dementia Rating (CDR) 2, fosgonimeton showed a larger effect size
mainly driven by an improvement in cognition at week 26.
- Patients with the highest baseline ADAS-Cog11 (>30) who were
treated with fosgonimeton (n=42) compared to placebo (n=52) showed
a -2.51 improvement in cognition as assessed by ADAS-Cog11
(p=0.16), for which a lower number represents improvement
- A small subset of patients with a CDR 2 (moderate dementia) who
were treated with fosgonimeton (n=20) compared to placebo (n=19)
showed a -3.74 improvement in cognition as assessed by ADAS-Cog11
(p=0.21)
Safety and TolerabilityFosgonimeton was generally well
tolerated, with a favorable safety profile. Participants treated
with fosgonimeton (40 mg) for 26 weeks showed a higher incidence of
treatment emergent adverse events compared to placebo, mainly
driven by injection site reactions. The incidence of serious
adverse events (SAEs) was similar between treatment groups, with
few treatment-related SAEs and no deaths observed in the study. The
study had a 22 percent early termination rate.
“In addition to fosgonimeton, we have a pipeline of
next-generation, orally delivered HGF modulators, with improved
pharmacological properties, that we are
currently evaluating in neurodegenerative diseases,”
stated Mark Litton, Ph.D., President and Chief Executive Officer of
Athira. “We want to express our sincere appreciation for the
patients, caregivers, their families, and healthcare professionals
who participated in the LIFT-AD trial. I also want to thank all
Athira employees for their dedication and tireless contributions to
advancing the science to benefit patients battling
neurodegenerative diseases.”
Full analysis of these results is scheduled to be reviewed at
the 17th Annual Clinical Trials on Alzheimer’s Disease (CTAD)
taking place October 29 - November 1, 2024, in Madrid,
Spain.
Athira continues to evaluate ATH-1105, a next-generation, orally
administered, small molecule drug candidate in development for the
potential treatment of amyotrophic lateral sclerosis (ALS), AD, and
other neurodegenerative diseases. Athira is currently
conducting a first-in-human, dose escalation Phase 1 clinical trial
evaluating safety, tolerability and pharmacokinetics of ATH-1105 in
up to 80 healthy volunteers. Athira completed the first
cohort of healthy volunteers in June 2024 and expects trial
completion by year-end 2024, with a goal to be in ALS patients in
2025. ATH-1105’s potential is supported by a growing body of
preclinical evidence demonstrating improvements in nerve and motor
function, biomarkers of inflammation and neurodegeneration, and
survival in various models of ALS.
Live WebcastAthira management will host a live
webcast to discuss the LIFT-AD topline results at 4:30 PM Eastern
time today, Tuesday, September 3, 2024. The live webcast can be
accessed at Events and Presentations | Athira Pharma. The call can
also be accessed by phone at 800-715-9871, conference ID: 4911242.
A replay of the webcast will be available two hours after the call
and will be archived on the Events for approximately 90 days.
About Athira Pharma, Inc.Athira Pharma, Inc.,
headquartered in the Seattle, Washington area, is a late
clinical-stage biopharmaceutical company focused on developing
small molecules to restore neuronal health and slow
neurodegeneration. Athira aims to alter the course of neurological
diseases by advancing its pipeline of drug candidates that modulate
the neurotrophic HGF system. For more information,
visit www.athira.com. You can also follow Athira
on Facebook, LinkedIn, X (formerly known as
Twitter) and Instagram.
Forward-Looking StatementsThis communication
contains “forward-looking statements” within the meaning of Section
27A of the Securities Act of 1933, Section 21E of the Securities
Exchange Act of 1934 and the Private Securities Litigation Reform
Act of 1995. These forward-looking statements are not based on
historical fact and include statements regarding: Athira’s drug
candidates as potential treatments for Alzheimer’s disease,
amyotrophic lateral sclerosis, and other neurodegenerative
diseases; future development plans; the anticipated reporting of
data; the potential learnings from preclinical studies and other
nonclinical data, the LIFT-AD trial and the ongoing Phase 1 trial
of ATH-1105 and their ability to inform and improve future clinical
development plans; expectations regarding the potential efficacy
and commercial potential of Athira’s drug candidates; and Athira’s
ability to advance its drug candidates into later stages of
development. Forward-looking statements generally include
statements that are predictive in nature and depend upon or refer
to future events or conditions, and include words such as “may,”
“will,” “should,” “on track,” “would,” “expect,” “plan,” “believe,”
“intend,” “pursue,” “continue,” “suggest,” “potential, target” and
similar expressions. Any forward-looking statements are based on
management’s current expectations of future events and are subject
to a number of risks and uncertainties that could cause actual
results to differ materially and adversely from those set forth in
or implied by such forward-looking statements. These risks and
uncertainties include, but are not limited to, the data from
preclinical and clinical trials may not support the safety,
efficacy and tolerability of Athira’s drug candidates; development
of drug candidates may cease or be delayed; regulatory authorities
could object to protocols, amendments and other submissions; future
potential regulatory milestones for drug candidates, including
those related to current and planned clinical studies, may be
insufficient to support regulatory submissions or approval; Athira
may not be able to recruit sufficient patients for its clinical
trials; the outcome of legal proceedings that have been or may in
the future be instituted against Athira, its directors and
officers; possible negative interactions of Athira's drug
candidates with other treatments; Athira’s assumptions regarding
its financial condition and the sufficiency of its cash, cash
equivalents and investments to fund its planned operations may be
incorrect; adverse conditions in the general domestic and global
economic markets; the impact of competition; the impact of expanded
drug candidate development and clinical activities on operating
expenses; the impact of new or changing laws and regulations; as
well as the other risks detailed in Athira’s filings with the
Securities and Exchange Commission from time to time. These
forward-looking statements speak only as of the date hereof and
Athira undertakes no obligation to update forward-looking
statements. Athira may not actually achieve the plans, intentions,
or expectations disclosed in its forward-looking statements, and
you should not place undue reliance on the forward-looking
statements.
Investor & Media Contact:
Julie RathbunAthira
PharmaJulie.rathbun@athira.com206-769-9219
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