CAHmelia-203 Study of Tildacerfont in Adult
Classic Congenital Adrenal Hyperplasia (CAH) with Severe
Hyperandrogenemia Did Not Meet Primary Efficacy Endpoint
Positive Data from CAHptain-205 Study of
Tildacerfont in Pediatric Classic CAH Supports Further Dose-Ranging
Across Additional Dosing Cohorts
Topline Results from CAHmelia-204 Study of
Tildacerfont in Adult Classic CAH Evaluating Glucocorticoid (GC)
Reduction Anticipated in Third Quarter of 2024
Resource Prioritization and Cost Reductions
Extend Cash Runway Through End of 2025
Conference Call Today at 4:30 p.m. ET
Spruce Biosciences, Inc. (Nasdaq: SPRB), a late-stage
biopharmaceutical company focused on developing and commercializing
novel therapies for rare endocrine disorders with significant unmet
medical need, today announced topline results from its CAHmelia-203
study of tildacerfont in adult classic congenital adrenal
hyperplasia (CAH) and its CAHptain-205 study of tildacerfont in
pediatric classic CAH.
Spruce is investigating tildacerfont, a second generation,
once-daily oral antagonist of the CRF1 receptor, for the treatment
of classic CAH. The global CAHmelia program in adult classic CAH is
comprised of two Phase 2b studies designed to address the unmet
medical needs of two distinct populations of adult CAH patients.
CAHmelia-203 assesses androstenedione (A4) reduction in adult CAH
patients with severe hyperandrogenemia, while CAHmelia-204 assesses
glucocorticoid (GC) reduction, a potentially registrational
endpoint, in adult CAH patients on supraphysiologic GC doses with
normal or near normal levels of A4.
The Phase 2 CAHptain-205 study is focused on addressing the
unmet medical need in pediatric CAH patients, which represents
approximately 25% of the total patient population. The CAHmelia and
CAHptain programs seek to address the unmet medical need across the
entire spectrum of the CAH patient community, which has not seen a
new standard of care since GCs were introduced in the 1950s.
CAHmelia-203 Study of Tildacerfont in Adult Classic
CAH
CAHmelia-203 enrolled 96 subjects with a mean baseline A4 level
of 1,151 ng/dL, which is more than five times above the upper limit
of normal (ULN).
Data Highlights
- The clinical trial did not achieve the primary efficacy
endpoint of the assessment of dose response for the change in A4
from baseline to week 12.
- 200mg QD of tildacerfont demonstrated a placebo-adjusted
reduction from baseline in A4 of -2.6% at week 12 with a
non-significant p-value.
- Compliance with study medication and GC was low with
approximately 50% of patients reporting 80% or greater compliance,
resulting in lower-than-expected tildacerfont exposure.
- Tildacerfont was generally safe and well tolerated at all doses
with no treatment-related serious adverse events (SAEs). Most
adverse events were reported as mild to moderate.
“We are grateful to all the patients, families, study team and
investigators who supported the CAHmelia-203 clinical trial,” said
Javier Szwarcberg, M.D., M.P.H., Chief Executive Officer, Spruce
Biosciences. “CAHmelia-203 is the first study of its kind to
address a difficult-to-treat CAH patient population with severe and
more refractory hyperandrogenemia, which is often attributed to
challenging real-life compliance with daily GCs. We garnered
important data from this study which will inform ongoing
development of tildacerfont in adult classic CAH.”
Dr. Szwarcberg added, “Looking ahead to the third quarter of
2024, we are eager to report topline results from CAHmelia-204,
which is focused on assessing GC reduction, a potentially
registrational endpoint, in a different population of adult CAH
patients with relatively controlled A4 levels and historically
better adherence to GC therapy. Assuming positive results from
CAHmelia-204 and CAHptain-205, we plan to meet with the U.S. Food
and Drug Administration (FDA) and comparable foreign regulatory
authorities to outline the design of a registrational clinical
program in adult and pediatric classic CAH.”
CAHmelia-203 and 204 Baseline Characteristics Highlight Two
Distinct Patient Populations in Adult CAH with Differing Disease
Status and Treatment Goals
Patients in CAHmelia-203 enrolled with severe hyperandrogenemia,
as indicated with mean baseline A4 levels more than five times
above the ULN. By contrast, patients in CAHmelia-204 enrolled with
a mean baseline A4 value of 224 ng/dL, which is approximately the
ULN, with 66% of patients enrolled with androgenic control, which
is defined as having A4 values below the ULN at baseline.
Study Characteristics
CAHmelia-203
(N = 96)
CAHmelia-204
(N = 100)
Male/Female
(Proportion of Total Subjects)
47% Male
53% Female
47% Male
53% Female
Average Age
Age Ranges
32 Years Old
(18 – 65 Years Old)
33 Years Old
(18 – 64 Years Old)
Average Baseline Glucocorticoid (GC)
Dose1
27 mg/day
(14 mg/m2/day)
37 mg/day
(20 mg/m2/day)
Average Baseline Androstenedione (A4)
Level2
1,151 ng/dL
(>5x ULN)
224 ng/dL
(~ULN)
Average Baseline 17-Hydroxyprogesterone
(17-OHP) Level2
16,653 ng/dL
(>80x ULN)
5,675 ng/dL
(>28x ULN)
Average Baseline Adrenocorticotropic
(ACTH) Level2
435 pg/dL
(>6x ULN)
168 pg/dL
(>2x ULN)
Body Mass Index (BMI)
50% Obese
(BMI ≥ 30 kg/m2)
53% Obese
(BMI ≥ 30 kg/m2)
1 In hydrocortisone equivalents (HCe)
2 Pre-GC dose.
“The CAHmelia-203 results underscore the complexities inherent
in managing a patient group with challenges related to androgenic
control and GC compliance,” said Irina Bancos, M.D., Principal
Investigator and Associate Professor of Medicine and
Endocrinologist at the Mayo Clinic. “Based on my clinical
experience, patients within this group may face difficulties
adhering to any therapeutic interventions, potentially impacting
treatment outcomes.”
Dr. Bancos continued, “Patients with higher glucocorticoid doses
and normal or near normal androgen levels, such as those enrolled
in CAHmelia-204, are generally more consistent with GC therapy and
easier to manage due to lower ACTH overdrive of the adrenal gland
but carry higher risk of glucocorticoid-associated comorbidities. I
look forward to reviewing results from CAHmelia-204, which will
provide a more complete picture into the therapeutic potential of
tildacerfont.”
CAHptain-205 Study of Tildacerfont in Pediatric Classic
CAH
CAHptain-205 enrolled 30 children between two and 17 years of
age with a mean baseline GC dose of 14 mg/m2/day and mean baseline
A4 level of 372 ng/dL. The study characterized the safety and
pharmacokinetic profiles of tildacerfont, as well as changes in
androgen levels over 12 weeks of treatment, and the ability to
reduce daily GC dose upon A4 normalization.
Data Highlights
- Tildacerfont was generally safe and well tolerated at all dose
ranges with no treatment-related SAEs reported.
- Preliminary pharmacokinetic analysis suggests that tildacerfont
is cleared more rapidly in children than in adult CAH
patients.
- 73% of all patients (22 of 30 patients) met the efficacy
endpoint of A4 or GC reduction from baseline at 12 weeks of
treatment with tildacerfont.
- 70% of patients with elevated baseline A4 values (16 of 23
patients) demonstrated an A4 reduction at week 4.
“As a pediatric endocrinologist, I’ve witnessed first-hand the
significant unmet medical need and lack of treatment options for
children and adolescents living with CAH,” said Will Charlton,
M.D., M.A.S., Chief Medical Officer, Spruce Biosciences. “The
CAHptain-205 study results demonstrate safety and tolerability in
pediatric CAH patients with weight-adjusted tildacerfont doses up
to 200mg daily. While we are encouraged by the therapeutic activity
of doses investigated in the study, we plan to continue
dose-ranging across additional cohorts to evaluate dose selection
to inform our registrational program. We anticipate topline results
in the fourth quarter of 2024.”
“I’m encouraged by the initial results from the CAHptain-205
study and the potential of tildacerfont to shift the treatment
paradigm for pediatric classic CAH to a more balanced approach
between androgens and GCs,” said Paul Thornton, M.B.B.S., Principal
Investigator and Medical Director of the Endocrine and Diabetes
Program at a CAH Center of Excellence. “These data suggest that
tildacerfont may enable clinically meaningful reduction of A4 and
GC levels in children and adolescents. This may improve long-term
clinical outcomes, such as short stature and obesity, which are
related to both androgen excess and exposure to chronic
supraphysiologic GC doses.”
Business and Financial Update
The company intends to implement cost savings initiatives,
including termination of the CAHmelia-203 study and a workforce
reduction of approximately 21%. The company currently has over $81
million in cash and cash equivalents, which is anticipated to fund
its current operating plan through the end of 2025, including
through the CAHmelia-204 topline results and CAHptain-205 topline
results from additional dosing cohorts.
Conference Call Details
Spruce’s management team and key study investigators will host a
conference call today at 4:30 p.m. ET to discuss the topline
results of the CAHmelia-203 and CAHptain-205 clinical studies.
Analysts and investors can participate in the conference call by
registering here or dialing (866) 777-2509.
An archived copy of the call will be available on the events
section of the company’s investor relations website for
approximately 90 days.
About CAHmelia-203
CAHmelia-203 is a randomized, double-blind, placebo-controlled,
dose-ranging Phase 2b clinical trial evaluating the safety and
efficacy of tildacerfont in 96 adults with classic CAH and highly
elevated levels of A4 at baseline while on stable glucocorticoid
dosing. For the first six weeks, patients received blinded placebo
to assess their adherence to their existing glucocorticoid therapy.
Patients who continued to meet all eligibility criteria at the end
of this period and where compliant with therapy entered a
three-part treatment period. During the placebo-controlled
treatment period, patients randomized in a blinded manner to
receive placebo, 50mg, 100mg, or 200mg tildacerfont once daily.
Dosing in the placebo-controlled treatment period continued for 12
weeks. The primary endpoint of the clinical trial was the
assessment of dose response for the change in A4 from baseline to
week 12. Following the placebo-controlled treatment period, all
patients received tildacerfont following a dose-escalation protocol
that allowed dose increase to 200mg once daily over 12 weeks.
Following the 12-week dose-escalation period, all patients
continued receiving tildacerfont at 200mg once daily for an
additional 46 weeks. Patients who achieved control of A4 while on
supraphysiologic glucocorticoid treatment had the opportunity to
reduce their glucocorticoid dosing in the open-label period
according to a pre-specified algorithm in the protocol. For more
information about the CAHmelia program, please visit
https://www.sprucebio.com/cahmelia.
About CAHmelia-204
CAHmelia-204 is a randomized, double-blind, placebo-controlled
Phase 2b clinical trial to evaluate the safety and efficacy of
tildacerfont in reducing glucocorticoid usage in 100 adults with
classic CAH on supraphysiologic doses of glucocorticoids with
normal or near normal levels of A4 at baseline. This clinical trial
is designed in two parts. In the first part of the clinical trial,
patients will be randomized to receive 200mg tildacerfont once
daily or placebo for 24 weeks. During the second part of the
clinical trial, all patients will receive open-label 200mg
tildacerfont once daily for 52 weeks. Throughout the trial,
tapering of glucocorticoids will be guided according to a
pre-specified algorithm and continue to the lowest level possible
(physiologic replacement levels), as long as patients remain well
controlled based on standard biomarkers and clinical assessments.
The primary endpoint of this clinical trial is the absolute change
in daily glucocorticoid dose from baseline at week 24. For more
information about the CAHmelia program, please visit
https://www.sprucebio.com/cahmelia.
About CAHptain-205
CAHptain-205 is a Phase 2 open-label clinical trial, which
utilized a sequential three cohort design, to evaluate the safety,
efficacy, and pharmacokinetics of tildacerfont in children two to
17 years of age. The study will also characterize changes in
androgen levels over 12 weeks of treatment, and the ability to
reduce daily glucocorticoid dose based on A4 normalization. An
optional open-label extension period will provide additional
open-label treatment with tildacerfont to provide long-term safety
data for up to two years. Cohort 1 enrolled five participants
between the ages of 11 and 17 years of age, who received a
weight-adjusted, adult dose equivalent of 50mg QD of tildacerfont.
Cohort 2 enrolled seven participants between the ages of 11 and 17
years of age, who received a weight-adjusted, adult dose equivalent
of 200mg QD of tildacerfont. Cohort 3 enrolled 18 participants
between the ages of two and 10 years of age, who received a
weight-adjusted, adult dose equivalent of 200mg QD of tildacerfont.
The primary endpoint of this clinical trial is safety. Additional
secondary endpoints include the proportion of subjects who achieve
reduction in A4 or daily glucocorticoid dosing at week 12 and the
proportion of subjects with elevated A4 at baseline who achieve a
reduction in A4 at week 4. For more information about the CAHptain
program, please visit https://www.sprucebio.com/cahptain.
About Congenital Adrenal Hyperplasia (CAH)
CAH is an autosomal recessive disease, driven by a mutation in
the gene that encodes an enzyme necessary for the synthesis of key
adrenal hormones. In CAH patients, the body is not able to produce
cortisol, leading to serious health consequences. The absence of
cortisol alters the normal feedback cycle of the
hypothalamic-pituitary-adrenal (HPA) axis and leads to excess
secretion of adrenocorticotropic hormone (ACTH), hyperplasia of the
adrenal gland, and consequently high levels of adrenal androgen
production. As a result, CAH patients may suffer from premature
puberty, impaired fertility, hirsutism, acne, the development of
adrenal rest tumors, and an impaired quality of life, and
additionally for females, virilized genitalia and menstrual
irregularities. Currently, the only way to downregulate the
production of excess androgens in CAH patients is to administer
supraphysiologic doses of glucocorticoids, which present specific
side effects, including increased risks of developing diabetes,
cardiovascular disease, stunted growth, osteoporosis, thin skin,
gastrointestinal disorders, and decreased lifespan.
About Tildacerfont
Tildacerfont is a potent and highly selective, non-steroidal,
once-daily oral antagonist of the CRF1 receptor, which is the
receptor for corticotropin-releasing factor (CRF), a hormone that
is secreted by the hypothalamus. The CRF1 receptor is abundantly
expressed in the pituitary gland where it is the primary regulator
of the HPA axis. By blocking the CRF1 receptor, tildacerfont has
the potential to address the uncontrolled cortisol feedback
regulatory pathway in CAH, and in turn reduce the production of
ACTH in the pituitary, limiting the amount of androgen produced
downstream from the adrenal gland. By controlling excess adrenal
androgens through an independent mechanism, tildacerfont has the
potential to reduce the unwanted clinical symptoms associated with
high androgen exposure and could also enable treating physicians to
lower the supraphysiologic glucocorticoid doses given to CAH
patients to near physiologic levels. No drug-related serious
adverse events have been reported related to tildacerfont treatment
in completed studies.
About Spruce Biosciences
Spruce Biosciences is a late-stage biopharmaceutical company
focused on developing and commercializing novel therapies for rare
endocrine disorders with significant unmet medical need. Spruce is
initially developing its wholly-owned product candidate,
tildacerfont, as the potential first non-steroidal, once-daily
therapy for patients suffering from classic congenital adrenal
hyperplasia (CAH) and other endocrine disorders. To learn more,
visit www.sprucebio.com and follow us on X, LinkedIn, Facebook, and
YouTube.
Forward-Looking Statements
Statements contained in this press release regarding matters
that are not historical facts are “forward-looking statements”
within the meaning of the Private Securities Litigation Reform Act
of 1995. Such forward-looking statements include statements
regarding, among other things, the design, results, conduct,
progress and timing of Spruce’s clinical trials; tildacerfont’s
potential to be a novel treatment option that improves long-term
health outcomes for patients with CAH; the implications of the
different patient population in CAHmelia-204 compared with
CAHmelia-203; Spruce’s expectations regarding reporting results of
its clinical trials in 2024; Spruce’s plans to meet with the FDA
and comparable foreign regulatory authorities to discuss the
potential registrational path forward of tildacerfont for adult and
pediatric classic CAH; the impact of cost savings initiatives and
the length of Spruce’s anticipated cash runway; and Spruce’s
product candidate, strategy and regulatory matters. Because such
statements are subject to risks and uncertainties, actual results
may differ materially from those expressed or implied by such
forward-looking statements. Words such as “anticipate”, “will”,
“potential”, “plan” and similar expressions are intended to
identify forward-looking statements. These forward-looking
statements are based upon Spruce’s current expectations and involve
assumptions that may never materialize or may prove to be
incorrect. Actual results could differ materially from those
anticipated in such forward-looking statements as a result of
various risks and uncertainties, which include, without limitation,
risks and uncertainties associated with Spruce’s business in
general, the impact of geopolitical and macroeconomic events, and
the other risks described in Spruce’s filings with the U.S.
Securities and Exchange Commission. All forward-looking statements
contained in this press release speak only as of the date on which
they were made and are based on management’s assumptions and
estimates as of such date. Spruce undertakes no obligation to
update such statements to reflect events that occur or
circumstances that exist after the date on which they were made,
except as required by law.
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version on businesswire.com: https://www.businesswire.com/news/home/20240313147623/en/
Media Will Zasadny Inizio Evoke Comms (619) 961-8848
will.zasadny@inizioevoke.com media@sprucebio.com Investors
Samir Gharib President and CFO Spruce Biosciences, Inc.
investors@sprucebio.com
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