Corbus Pharmaceuticals Holdings, Inc. (NASDAQ: CRBP) (“Corbus” or
the “Company”), an immunology company developing innovative
medicines that target inflammation,
fibrosis, metabolism and immuno-oncology, today
announced topline results from the Phase 3
DETER
MINE study of lenabasum in
adults with the rare, heterogeneous, autoimmune disease
dermatomyositis.
Primary endpoint:
The study did not meet its primary endpoint of
Total Improvement Score (TIS) at Week 28. Higher TIS values
indicate greater overall improvement. At Week 28, the lenabasum 20
mg twice daily group achieved a mean TIS of 28.3 versus the control
group mean TIS of 26.7, p = 0.1965. All subjects, including the
control group, received standard background treatments, with 89% of
dosed subjects receiving ≥ 1 immunosuppressive or immunomodulating
therapy. Additional pre-specified analyses of the overall effect on
TIS of lenabasum 20 mg twice daily versus control group through
Week 52 showed a trend of beneficial effect of lenabasum, nominal p
= 0.0795.
Additional findings:
Dermatomyositis patients have characteristic
muscle weakness and inflammatory skin involvement. This study
enrolled subjects with the two major types of dermatomyositis:
classic dermatomyositis with both muscle weakness and skin
involvement and dermatomyositis with no significant muscle weakness
but with skin involvement. Improvement in muscle weakness is
heavily weighted in the TIS score. In the overall study, higher TIS
scores were seen in those subjects who had muscle weakness (Manual
Muscle Test-8 muscle group score < 142) and were treated with
lenabasum 20 mg twice daily versus the control group, nominal p =
0.0302. Conversely, the Cutaneous Dermatomyositis Activity and
Severity Index (CDASI) activity score, a secondary endpoint in this
study, is a validated outcome that was designed to assess
inflammatory skin involvement in dermatomyositis. In the overall
study, greater improvement (reduction) in CDASI activity scores was
seen in subjects with skin involvement but no muscle weakness who
were treated lenabasum 20 mg twice daily versus the control group,
nominal p = 0.0166. This is a similar patient population and the
same endpoint as was tested in Corbus’ previously completed Phase 2
study (ClinicalTrials.gov Identifier: NCT02466243).
Effect of lenabasum on lung function was a
secondary endpoint in this study, and no statistically significant
difference was seen at Week 28 in the lenabasum 20 mg twice daily
group versus control group. In the overall study, other
pre-specified analyses showed that subjects on stable
immunosuppressive therapies (> 1 year treatment duration) had an
improvement in forced vital capacity compared to the control group,
nominal p = 0.0591.
Efficacy results for the lenabasum 5 mg twice
daily group were generally similar to those for the control
group.
Safety:
Safety data showed 86.5% of lenabasum-treated
subjects and 85.9% of control subjects had treatment-emergent
adverse events (AEs), 11.5% of lenabasum-treated subjects and 5.6%
of control subjects had serious AEs, and no lenabasum-treated
subject and 1 control subject discontinued study drug because of an
AE related to study drug. Adverse events that occurred in ≥ 10%
lenabasum-treated subjects and also in ≥ 5% more lenabasum-treated
subjects than control subjects were diarrhea (12.5% versus 7.0%),
dizziness (10.6% versus 4.2%), and nausea (10.6% versus 4.2%).
There were fewer AEs of dermatomyositis worsening in the lenabasum
20 mg twice daily group than the control group (27 versus 44).
Data from this study will be presented at an
upcoming medical conference.
“We are disappointed that the trial did not meet
the primary endpoint of TIS at Week 28,” said Barbara White, M.D.,
Chief Medical Officer and Head of Research at Corbus. “Nonetheless,
we are encouraged by the results when the outcome is matched to the
subtype of dermatomyositis in the study. We believe we see clinical
activity of lenabasum 20 mg administered twice daily compared to
the control group just receiving standard background treatments,
with higher TIS scores in classic dermatomyositis subjects with
muscle weakness and skin involvement and greater reduction in CDASI
activity score in subjects with active skin disease but normal
muscle strength. We thank the participants, investigators and
clinical site study staff, and the patient advocacy community for
their support of this study.”
Victoria Werth, M.D., Professor of Dermatology
and Medicine, University of Pennsylvania Perelman School of
Medicine and Chief of Dermatology, Corporal Michael J. Crescenz
VAMC, said, “I’m pleased by the improvement in CDASI activity
scores seen in dermatomyositis patients with minimal active muscle
disease in this study. It is difficult to conduct a large
stand-alone study in just this small subtype of patients. In such a
complex disease, seeing this subtype with refractory skin disease
respond so well in this and the Phase 2 study is promising. These
patients frequently have widespread disfiguring, symptomatic and
refractory skin manifestations, and there is a need for new
treatments, especially those that are not immunosuppressive. Our
skin biomarker data from Phase 2 show reductions in inflammatory
cytokines and T cells with lenabasum treatment compared to placebo,
supporting improvement in skin disease in these patients. The
improvement in TIS in subjects with muscle weakness is also
interesting. It is clear to me that we have to look at the organs
that are involved and use outcomes that correspond to those organs
to detect change in dermatomyositis.”
Yuval Cohen, Ph.D., Chief Executive Officer,
commented, “We look forward to discussing the data from the Phase 2
and Phase 3 dermatomyositis studies with regulatory authorities and
seeking their input on next steps. With our strong cash position,
we have the resources to both advance our now diversified pipeline
while also planning next steps for lenabasum.”
DETERMINE
Phase 3 Study Design
The Phase 3 trial evaluated the safety and
efficacy of lenabasum in adults with active classic or amyopathic
dermatomyositis who were receiving standard treatments. This
international study dosed 175 subjects who were randomized 2:1:2 to
receive lenabasum 20 mg twice per day (n = 69), lenabasum 5 mg
twice per day (n = 35), or placebo twice per day (n = 71), all
added to background treatments. The primary efficacy endpoint was
the composite American College of Rheumatology/European League
Against Rheumatism 2016 Total Improvement Score at Week 28,
comparing lenabasum 20 mg twice daily versus placebo. Change in
CDASI activity score and forced vital capacity were among secondary
efficacy endpoints. As previously disclosed, in this study of up to
one year duration, the timing of the primary efficacy endpoint was
changed from Week 52 to Week 28.
About Lenabasum
Lenabasum is a novel, oral, small molecule
designed to provide an alternative to immunosuppressive treatments
for inflammatory or fibrotic diseases. Lenabasum binds to and
activates the cannabinoid receptor type 2 (CB2), which is
preferentially expressed on activated immune cells, to resolve
inflammation and limit fibrosis. Data from animal models and human
clinical studies suggest that lenabasum can reduce expression of
genes and proteins involved in inflammation and fibrosis. In
clinical testing to date, lenabasum has acceptable safety and
tolerability profiles.
About Dermatomyositis
Dermatomyositis, a form of idiopathic
inflammatory myositis, is a chronic, rare, inflammatory, clinically
heterogenous, and sometimes life-threatening autoimmune disease
affecting approximately 80,000 people in North America, EU and
Japan.1 The signs and symptoms of dermatomyositis reflect
multi-organ involvement, which includes distinctive skin rashes
usually accompanied by proximal muscle weakness, and can also
include pulmonary, cardiac, gastrointestinal, and joint
involvement.2 Patients with dermatomyositis can have recurrent
disease flares or chronic progressive disease activity, with
increased mortality.3,4 The current mainstay of treatments include
FDA-approved systemic glucocorticoids and off-label use of
glucocorticoid-sparing immunosuppressive or immunomodulating
agents.5,6 There is significant unmet need for new treatments to
achieve disease control in dermatomyositis because of limited
efficacy or toxicity of immunosuppressive agents or refractory
disease.7,8
About Corbus
Corbus is committed to connecting innovation to
our purpose of improving lives by developing new medicines that
target inflammation, fibrosis, metabolism and immuno-oncology, by
building upon our underlying expertise in immunology. Corbus’
current pipeline includes small molecules that activate or inhibit
the endocannabinoid system and anti-integrin monoclonal antibodies
that block activation of TGFβ. Corbus is headquartered in Norwood,
Massachusetts. For more information on Corbus, visit
corbuspharma.com. Connect with us on Twitter, LinkedIn
and Facebook.
Forward-Looking Statements
This press release contains certain
forward-looking statements within the meaning of Section 27A of the
Securities Act of 1933 and Section 21E of the Securities Exchange
Act of 1934 and Private Securities Litigation Reform Act, as
amended, including those relating to the Company's restructuring,
trial results, product development, clinical and regulatory
timelines, market opportunity, competitive position, possible or
assumed future results of operations, business strategies,
potential growth opportunities and other statement that are
predictive in nature. These forward-looking statements are based on
current expectations, estimates, forecasts and projections about
the industry and markets in which we operate and management's
current beliefs and assumptions.
These statements may be identified by the use of
forward-looking expressions, including, but not limited to,
"expect," "anticipate," "intend," "plan," "believe," "estimate,"
"potential,” "predict," "project," "should," "would" and similar
expressions and the negatives of those terms. These statements
relate to future events or our financial performance and involve
known and unknown risks, uncertainties, and other factors,
including the potential impact of the recent COVID-19 pandemic and
the potential impact of sustained social distancing efforts, on our
operations, clinical development plans and timelines, which may
cause actual results, performance or achievements to be materially
different from any future results, performance or achievements
expressed or implied by the forward-looking statements. Such
factors include those set forth in the Company's filings with the
Securities and Exchange Commission. Prospective investors are
cautioned not to place undue reliance on such forward-looking
statements, which speak only as of the date of this press release.
The Company undertakes no obligation to publicly update any
forward-looking statement, whether as a result of new information,
future events or otherwise.
Corbus Pharmaceuticals
Contacts:
Ted Jenkins, Senior Director, Investor Relations
and Corporate Communications Phone: +1 (617) 415-7745 Email:
ir@corbuspharma.com
Lindsey Smith, Director, Investor Relations and
Corporate Communications Phone: +1 (617) 415-7749 Email:
mediainfo@corbuspharma.com
- Health Advances, LLC Analysis
- “Dermatomyositis Information Page.”
National Institute of Neurological Disorders and Stroke, U.S.
Department of Health and Human Services, 23 June 2021,
www.ninds.nih.gov/Disorders/All-Disorders/Dermatomyositis-Information-Page
- Marie, Isabelle. “Morbidity and
Mortality in Adult Polymyositis and Dermatomyositis.” Current
Rheumatology Reports, vol. 14, no. 3, 2012, pp. 275–285.,
doi:10.1007/s11926-012-0249-3
- Schiopu, Elena, et al. “Predictors
of Survival in a Cohort of Patients with Polymyositis and
Dermatomyositis: Effect of Corticosteroids, Methotrexate and
Azathioprine.” Arthritis Research & Therapy, vol. 14, no. 1,
2012, doi:10.1186/ar3704
- FDA label Orapred ODT, available at
https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/021959s004lbl.pdf;
accessed 23 June 2021
- FDA label H.P. Acthar gel, available at
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/008372s057lbl.pdf;
accessed 23 June 2021
- Dalakas, Marinos C. “Immunotherapy
of Myositis: Issues, Concerns and Future Prospects.” Nature Reviews
Rheumatology, vol. 6, no. 3, Mar. 2010, pp. 129–137.,
doi:10.1038/nrrheum.2010.2
- DeWane ME, et al. Dermatomyositis:
Clinical features and pathogenesis. J Am Acad Dermatol.
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