Full Press Release Details
Edgewise Therapeutics Announces Positive Topline
Results from the CANYON Phase 2 Trial of Sevasemten in Individuals with Becker Muscular Dystrophy (Becker)
- Trial met primary endpoint of reduction
in circulating levels of creatine kinase (CK), a biomarker associated with skeletal muscle damage, in the largest Becker interventional
- On the key secondary endpoint, sevasemten-treated
patients showed stabilization of North Star Ambulatory Assessment (NSAA) with a trend towards improvement at 12 months compared to placebo
- Sevasemten was well-tolerated and
no new safety concerns were observed -
- Edgewise leadership to discuss CANYON
findings on Monday, December 16 at 8:30 a.m. Eastern Time at a virtual investor event -
Boulder, Colo., (December 16, 2024) - Edgewise
Therapeutics, Inc., (Nasdaq: EWTX), a leading muscle disease biopharmaceutical company, today announced positive topline results
from the Phase 2 CANYON trial of sevasemten in individuals with Becker muscular dystrophy. Sevasemten is an orally administered first-in-class
fast skeletal myosin inhibitor designed to protect muscle against contraction-induced damage in muscular dystrophies. The trial met its
primary endpoint of change from baseline in CK. CANYON is the largest interventional trial to date in Becker and the first to achieve
its primary endpoint.
NSAA, the key secondary endpoint of function, showed a trend towards
improvement over time in the sevasemten-treated group. Plasma fast skeletal muscle troponin I (TNNI2), a target-specific biomarker of
fast skeletal muscle damage, showed a significant reduction, compared to placebo. Additional functional measures, including the 10-meter
walk/run, 4-stair climb and 100-meter timed test, showed trends towards improvement compared to placebo. Notably, the treatment population
had more advanced disease than placebo.
Sevasemten was well-tolerated, and no new safety concerns were observed
in either the adult or adolescent patient populations. Ninety-nine percent of eligible participants from CANYON and other sevasemten trials
in Becker have enrolled in MESA, the ongoing open label extension trial.
"Becker muscular dystrophy is a devastating neuromuscular disease
characterized by rapid progression once functional decline begins. This landmark study presents compelling biomarker data and promising
signals that suggest the potential for functional stabilization with administration of sevasemten," said Craig M. McDonald, M.D.,
Distinguished Professor and Chair at the UC Davis Health Department of Physical Medicine and Rehabilitation, and a Principal Investigator
in CANYON and GRAND CANYON. "Becker has no approved therapies. I look forward to the results of the GRAND CANYON pivotal cohort
with the hope of bringing the first treatment option to this patient population."
"We are very encouraged by the CANYON results
in Becker and the potential of this novel muscle-targeted therapeutic," said Joanne Donovan, Ph.D., M.D., Chief Medical Officer,
Edgewise. "This confirmed our previous observations in the ARCH study of significant decreases in biomarkers of muscle damage and
similarly we are seeing evidence of preservation of function in Becker patients."
The Company is on track to complete recruitment
in the GRAND CANYON cohort by the first quarter of 2025. Based on these positive Phase 2 results, the Company plans to engage the U.S.
Food and Drug Administration (FDA) and European Medicines Agency about marketing authorization filing strategies for sevasemten in Becker.
The Company intends to submit the complete results of the CANYON study
for publication at a future medical congress.
Overview of CANYON and Clinical Results
CANYON, the largest interventional Becker trial, is a Phase
2, double-blind, randomized, placebo-controlled study to investigate the effect of sevasemten on the safety, pharmacokinetics, biomarkers,
and functional measures of participants (NCT05291091). The trial was not powered for the functional endpoints. Forty adults and
29 adolescents with Becker muscular dystrophy were enrolled. This study had a 4-week screening period, a 12-month treatment period, followed
by a 4-week follow-up period. The adult participants were randomized to sevasemten or placebo in a 3:1 ratio. The adolescent participants
were randomized in a 2:1 ratio to sevasemten or placebo and were assessed for safety and tolerability. The data analysis included the
complete adult safety population of 40 individuals. There was a notable imbalance between adult participants in the sevasemten and placebo
groups with the sevasemten group having more advanced disease at baseline based on all functional measures and MRI.
Primary Endpoint: The primary endpoint to assess the efficacy
of sevasemten compared to placebo was change from baseline in CK over the treatment period for adults. The results demonstrated a significant
change from baseline in CK in the sevasemten-treated group (difference vs. placebo, 28% average decrease over months 6 through 12; p=0.02).
Key Secondary Endpoint: The key secondary endpoint was the change
from baseline in NSAA total score in adults at month 12. NSAA is a scale commonly used to rate motor function. The between-group difference
was 1.1 points, favoring sevasemten; p=0.16 across all adult participants. NSAA remained stable over time in the sevasemten treatment
group, similar to the observations in the ARCH study. Further, while the placebo group was small in number (n=12), NSAA declined similarly
to that observed in previous natural history studies.1,2,3
Other Secondary Endpoints: Plasma TNNI2 decreased 77% from baseline
in the sevasemten-treated group compared to placebo, averaged over months 6 through 12 in adults; p<0.001.
The 10-meter walk/run, 4-stair climb and 100-meter timed test showed
trends towards improvement, compared to placebo. The Company continues to evaluate additional secondary and exploratory endpoints.
Safety and Tolerability: Sevasemten was well-tolerated, and
no new safety concerns were identified.
CANYON Implications to GRAND CANYON: The functional observations
from the CANYON study support that the GRAND CANYON pivotal cohort's primary endpoint is powered at >95% to demonstrate a statistically
significant NSAA difference at 18 months.
MESA, open label extension trial in adults with Becker: The
Company is advancing MESA, an open-label extension trial to assess the long-term effect of sevasemten in individuals with Becker. MESA
provides continued access to sevasemten to participants who were previously enrolled in ARCH, or completed CANYON, GRAND CANYON, or DUNE.
To date, 99% of eligible participants completing these trials have enrolled in MESA.
GRAND CANYON, a global pivotal cohort in Becker: GRAND CANYON,
an expansion of the CANYON placebo-controlled trial, is a multi-center, randomized, double-blind, placebo-controlled cohort to evaluate
the safety and efficacy of sevasemten in adults with Becker. The primary endpoint of GRAND CANYON is change from baseline in NSAA at
18 months. In addition, other functional assessments, biomarkers of muscle damage, MRI, patient-reported outcomes and safety will be
assessed. GRAND CANYON is an 18-month cohort anticipated to recruit approximately 120 individuals with Becker. Data from GRAND CANYON,
if positive, could support a marketing application. To learn more, go to clinicaltrials.gov (NCT05291091).
Sevasemten has achieved notable regulatory milestones by securing FDA
Orphan Drug Designation for the treatment of Becker and Duchenne, Rare Pediatric Disease Designation (RPDD) for the treatment of Duchenne,
and Fast Track designations for the treatment of Becker and Duchenne. Further, sevasemten secured the EMA Orphan Drug Designations for
the treatment of Becker and Duchenne.
Upcoming CANYON Data Presentations:
Virtual Investor Event
Members of the Edgewise management team will
hold a live webcast on Monday, December 16, at 8:30 a.m. ET to discuss the CANYON data, and will be joined by Dr. McDonald,
who will share his perspective of sevasemten and Becker. An accompanying slide presentation will also be available. To register for the
live webcast and replay, please visit the Edgewise events page.
Patient Community Webinar
Members of Edgewise management will hold a community
webinar on Wednesday, December 18, 2024, at 1 p.m. ET to discuss these data and the GRAND CANYON pivotal study. To register
for the community webinar, please click here.
About Becker Muscular Dystrophy
Becker is a rare, genetic, life-shortening, debilitating
and degenerative neuromuscular disorder. The disease predominantly affects males and imposes significant physical, emotional, financial,
and social impacts on the individual and their caregivers. Individuals with Becker experience contraction-induced muscle damage, which
is the primary driver of muscle loss and impaired motor function in muscular dystrophies. Functional decline can begin at any age, and
once that muscle loss occurs, the decline in function is irreversible and continues throughout the individual's life. Some individuals
living with Becker experience heart failure from cardiomyopathy, which may result in heart transplantation or early death. Currently,
there is no cure for Becker; early and long-term multidisciplinary care is critical for optimized disease management. There is a great
need for more Becker-specific scientific research, clinical programs, and treatment guidelines to improve management of this disease.
To learn more about Becker, go to https://beckermusculardystrophy.com/
About Sevasemten (EDG-5506) for Becker and