Full Press Release Details
Edgewise Therapeutics Reports First Quarter
2024 Financial Results and Recent Business Highlights
- Announced positive two-year topline
results of sevasemten ARCH open label trial and
advanced GRAND CANYON pivotal cohort in Becker -
-Positive interim topline data
for DUNE trial of sevasemten in Becker -
Expanded Phase 2 LYNX trial of sevasemten in Duchenne -
- Anticipated to overenroll
Phase 2 FOX trial in Duchenne boys previously treated with gene therapy -
- Initiated Phase 2 CIRRUS-HCM
trial of EDG-7500 in patients with obstructive HCM -
(May 9, 2024) - Edgewise Therapeutics, Inc., (Nasdaq: EWTX), a leading muscle disease biopharmaceutical
company, today reported financial results for the first quarter of 2024 and recent business highlights.
to a great start with tremendous progress on our skeletal and cardiac muscle programs," said Kevin Koch, Ph.D., President
and Chief Executive Officer of Edgewise. "Most recently, we initiated our Phase 2 CIRRUS-HCM trial of EDG-7500 and announced positive
2-year topline data from our ARCH open label trial in Becker. We expect significant catalysts on our programs throughout this year including
data from the CANYON and CIRRUS studies."
Musculoskeletal Program / Sevasemten
Becker Muscular Dystrophy (Becker)
an orally administered small molecule designed to prevent contraction-induced muscle damage in dystrophinopathies including Becker and
Duchenne muscular dystrophy. There are currently no approved therapies for individuals with Becker, a serious genetic, progressive neuromuscular
disorder with significant unmet need.
ARCH open-label trial in Becker: The
Company announced positive two-year topline results from the ARCH trial, an open label, single-center trial assessing safety,
tolerability, impact on muscle damage biomarkers, pharmacokinetics (PK) and functional measures with sevasemten in adults with
Becker. The ARCH trial evaluated sevasemten administered daily over two years in adults with Becker. Sevasemten was
well-tolerated in all 12 participants with no discontinuations or dose reductions due to adverse events. During two years
of sevasemten treatment, participants' North Star Ambulatory Assessment (NSAA) scores
stabilized and continued to diverge relative to declines reported across multiple Becker natural history studies.1, 2,3
In addition, significant decreases in key biomarkers of muscle damage including creatine kinase (CK) and fast skeletal muscle
troponin I (TNNI2) were observed in participants treated with sevasemten, which are consistent with prior observations. The
positive results from the two-year ARCH trial further support the hypothesis that a reduction in contraction-induced muscle damage
has the potential to preserve and improve muscle function and disease progression in Becker.
CANYON Phase 2 placebo-controlled trial in
adults with Becker: CANYON, the largest interventional Becker trial to date, includes 40 adults and 29 adolescents with a sevasemten
treatment period of 12 months. The primary endpoint of CANYON is change in CK over the treatment period with additional measures collected,
including NSAA, 100-meter timed test, biomarkers of muscle damage and MRI. The Company expects to report CANYON data in the fourth quarter
a global pivotal cohort in Becker: GRAND CANYON, an expansion of the CANYON placebo-controlled trial, is a multicenter, randomized,
double-blind, placebo-controlled study to evaluate the safety and efficacy of sevasemten in adults with Becker. The primary endpoint
of GRAND CANYON is change in NSAA. In addition, other functional assessments, biomarkers of muscle damage and safety will be assessed.
GRAND CANYON is an 18-month cohort anticipated to recruit approximately 120 individuals with Becker, aged between 18 and 50 years old
and a NSAA score between 5 and 32, at up to 50 sites in 10 countries. Data from GRAND CANYON, if positive, could support a marketing
application. To learn more, go to clinicaltrials.gov (NCT05291091) or the GRAND CANYON microsite: https://www.beckergcstudy.com.
Phase 2 Exercise Challenge trial in adults with Becker, LGMD2I or McArdle disease:
The Company continues to advance the DUNE Phase 2 Exercise Challenge study. This 16-week randomized, double-blind, placebo-controlled
study with an open label extension to 78 weeks, assesses safety, PK, and biomarker response to exercise in adults with Becker, limb-girdle
muscular dystrophy type 2I (LGMD2I) or McArdle disease. Unlike Becker, LGMD2I is a muscular dystrophy
caused by a dysfunctional dystroglycan complex while McArdle is caused by deficiencies in glycogen mobilization leading to metabolic crisis
and injury of skeletal muscle.
The study was designed with a
3-week screening period, which included a controlled exercise challenge and subsequent biomarker analysis, principally CK and TNNI2, followed
by a 16-week double-blind period in which participants were randomized 2:1 to receive once-daily treatment with sevasemten (15 mg) or
matching placebo. At week 12, participants underwent a second controlled exercise challenge to determine whether treatment with sevasemten
conferred protection against exercise induced muscle damage.
interim results showed that sevasemten was well tolerated across all 21 participants (Becker (n=9), LGMD2I (n=9) and McArdle (n=3)). Biomarker
reductions in the Becker cohort were consistent with results observed in the ARCH trial, including statistically significant decreases
in TNNI2 and CK versus patients on placebo; sevasemten treatment significantly reduced mean CK by 45% (p<0.05 vs placebo) and TNNI2
by 89% (p<0.05 vs placebo). Over the 24 hours post-exercise, sevasemten treatment also significantly reduced biomarkers of muscle damage
associated with exercise with a mean post-exercise reduction of CK of 49% (p<0.001 vs placebo) and TNNI2 of 75% (p=0.07 vs placebo).
Biomarker data from the LGMD2I and McArdle cohorts
are currently inconclusive and would likely require additional participants to interpret any response. The Company, in partnership with
Dr. John Vissing, the lead investigator for DUNE, are continuing to compile and analyze the data which will be presented in full at a
future medical meeting.
DUNE represents the first placebo-controlled trial
with sevasemten in individuals with Becker. The preliminary data from DUNE, combined with the 2-year observations from ARCH, continue
to support the hypothesis that protecting fast muscle fibers with sevasemten limits contraction-induced muscle damage and offers the potential
to halt disease progression in individuals with Becker.
Duchenne Muscular Dystrophy
trial in boys with Duchenne: LYNX is a 2-part multi-center, dose-finding Phase 2 trial to evaluate the effect of sevasemten
on safety, PK, and biomarkers of muscle damage in over 60 children aged 4 to 9 years with Duchenne treated with oral, once-daily sevasemten.
The trial will also explore changes in functional measures such as NSAA, stride velocity 95th centile (SV95%) and self-reported/caregiver-reported
outcomes. Part A of the trial will include a 12-week, randomized, double-blind, placebo-controlled dose ranging study period, followed
by Part B, a 92-week open-label extension. Dosing in Part B was adjusted to a previously studied dose, based on the interim analysis of
the higher dose for safety as well as assessment of biomarkers of muscle damage in that cohort.
LYNX was designed to identify a Phase 3 dose of
sevasemten that will reduce biomarkers of muscle damage and has the potential to provide functional benefit to individuals with Duchenne.
To date, across five cohorts, sevasemten achieved exposures predicted to provide benefit based on preclinical models and was observed
to be safe and well tolerated. Moreover, decreases in biomarkers of muscle damage with sevasemten treatment were observed. This observation
provides confidence that exposures are achieving target levels and the Company is initiating a 6th cohort to validate observations thus
to report LYNX data, including safety, PK, changes in biomarkers of muscle damage and functional changes in NSAA and SV95 in the fourth
quarter of 2024. The Company will rely on LYNX data, along with data from the FOX trial of Duchenne boys previously
treated with gene therapy, to guide the design and powering of a Phase 3 trial in Duchenne, planned to be initiated in the first
half of 2025. For more information on LYNX go to clinicaltrials.gov to learn more about this trial (NCT05540860).
trial in boys with Duchenne (previously treated with gene therapy): The Company is advancing FOX, a Phase 2 placebo-controlled
trial to assess the effect of sevasemten over 12 weeks on safety, PK and biomarkers of muscle damage in children and adolescents aged
6 to 14 years with Duchenne who have been previously treated with gene therapy. The trial will also explore changes in functional measures
such as NSAA, SV95% and self-reported/caregiver-reported outcomes. The Company expects to substantially overenroll the trial from the
original plan of 24 participants. There has been exceptional enthusiasm from the Duchenne community for this trial, evident in the Company's
ability to complete the trial's enrollment within two months. Go to clinicaltrials.gov to learn more about this trial (NCT06100887).
Drug from the European Medicines Agency (EMA) and Fast Track from the U.S. Food & Drug Administration (FDA): The EMA granted
Orphan Drug Designation (ODD) for sevasemten for the treatment of Becker and for the treatment of Duchenne in April 2024. The FDA granted
sevasemten Fast Track designation for the treatment of Duchenne in February 2024. The FDA previously granted ODD for the treatment of
Duchenne and Becker, Rare Pediatric Disease Designation for the treatment of Duchenne and Fast Track designation for sevasemten for the
treatment of Becker.
Cardiovascular Program / EDG-7500
EDG-7500 is a novel oral, selective, cardiac
sarcomere modulator, specifically designed to slow early contraction velocity and address impaired cardiac relaxation associated
with hypertrophic cardiomyopathy (HCM) and other diseases of diastolic dysfunction. Preclinical data in models of both obstructive
and non-obstructive HCM suggest the ability to drive a broadly effective clinical response at a low risk of decreasing left