Xeris Biopharma Holdings, Inc. (Nasdaq: XERS), a
biopharmaceutical company developing and commercializing unique
therapies for patient populations in endocrinology, neurology, and
gastroenterology, today announced it is presenting new data on the
burden of illness in Cushing’s syndrome (CS) and the double-blind,
placebo-controlled LOGICS study of Recorlev® (levoketoconazole) in
CS during the Pituitary Disorders/Neuroendocrinology ePoster
sessions at the American Association of Clinical Endocrinology
(AACE) Annual Meeting, May 12-14, 2022.
Levoketoconazole in the Treatment of Endogenous Cushing’s
Syndrome: A Double-Blind, Placebo-Controlled, Randomized Withdrawal
Study (abstract link here)
LOGICS, a phase 3 double-blind, placebo-controlled
randomized-withdrawal (RW) study evaluated the drug-specificity of
cortisol normalization in adults with CS by comparing the effect of
withdrawing levoketoconazole to placebo versus continuing
levoketoconazole treatment. The study, which included
titration-maintenance, randomized withdrawal and restoration
phases, met its previously reported primary endpoint of
significantly more patients on placebo having loss of mean
urinary-free cortisol (mUFC) response than those who continued on
levoketoconazole at end of RW phase. Restoration of
levoketoconazole therapy reversed loss of cortisol control in most
patients who had received placebo; of 20 placebo group patients
with mUFC >ULN at restoration phase baseline, 12 (60%) were
normalized at the end of the restoration phase. In the RW phase,
mean total and LDL cholesterol levels were significantly increased
with placebo versus levoketoconazole; these increases were reversed
during the restoration phase. Throughout the study, no new safety
signals of levoketoconazole treatment were identified, and known
risks were manageable with appropriate monitoring.
The full data will be shared during a poster presentation
scheduled for May 12, 1:00–1:15 PM (PST).
Patient-Reported Burden of Illness in Endogenous Cushing’s
Syndrome (abstract link here)
The burden of illness (BOI) study captured the burden and
health-related quality of life (HRQoL) associated with CS using
validated patient reported outcome (PRO) measures of CushingQoL,
Pain Visual Analog Scale (VAS), Brief Fatigue Inventory (BFI),
PROMIS Sleep Disturbance (T-score) and PROMIS Anxiety SF 8a
(T-score). Results showed that patients with CS experience a
substantial and multi-faceted HRQoL burden. On the CushingQoL
measure, respondents experienced moderate HRQoL impairment due to
CS. The mean VAS score was 3.6 out of 10, indicating relatively low
levels of pain; however, 89% of all respondents reported taking
over-the-counter analgesics to manage their symptoms. Patients
reported moderate/severe fatigue (BFI), and moderate sleep and
anxiety burden (PROMIS). Patients experienced symptoms of CS on
approximately half the days in a typical month, and those who were
employed missed 2 workdays every month, amounting to approximately
25 days per year due to CS.
The full data will be shared during a poster presentation
scheduled for May 12, 4:10–4:25 PM (PST).
About Cushing’s Syndrome
Endogenous Cushing’s syndrome is a rare, serious, and
potentially fatal endocrine disease caused by chronic elevated
cortisol exposure–often the result of a benign tumor of the
pituitary gland. This benign tumor tells the body to overproduce
high levels of cortisol for a sustained period of time, which often
results in characteristic physical signs and symptoms that are
distressing to patients. The disease is most common among adults
between the ages of 30–50, and it affects women three times more
often than men. Women with Cushing's syndrome may experience a
variety of health issues including menstrual problems, difficulty
becoming pregnant, excess male hormones (androgens), primarily
testosterone, which can cause hirsutism (growth of coarse body hair
in a male pattern), oily skin, and acne.3
Additionally, the multisystem complications of the disease are
potentially life threatening. These include metabolic changes such
as high blood sugar or diabetes, high blood pressure, high
cholesterol, fragility of various tissues including blood vessels,
skin, muscle, and bone, and psychological disturbances such as
depression, anxiety, and insomnia.3 Untreated, the five-year
survival rate is only approximately 50%.4
About Recorlev
Recorlev® (levoketoconazole) is a cortisol synthesis inhibitor
for the treatment of endogenous hypercortisolemia in adult patients
with Cushing’s syndrome for whom surgery is not an option or has
not been curative.1 Endogenous Cushing’s syndrome is a rare but
serious and potentially lethal endocrine disease caused by chronic
elevated cortisol exposure.2 Recorlev is the pure 2S,4R enantiomer
of ketoconazole, a steroidogenesis inhibitor.1 Recorlev has
demonstrated in two successful Phase 3 studies to significantly
reduce mean urine free cortisol.1
The Phase 3 program for Recorlev included SONICS and LOGICS, two
multinational studies designed to evaluate the safety and efficacy
of Recorlev when used to treat endogenous Cushing’s syndrome. The
SONICS study met its primary and secondary endpoints, significantly
reducing and normalizing mean urinary free cortisol concentrations
without a dose increase.1,2 The LOGICS study, which met its primary
endpoint and key secondary endpoint, was a double-blind,
placebo-controlled randomized-withdrawal study of Recorlev that was
designed to supplement the efficacy and safety information provided
by SONICS.1 The ongoing open-label OPTICS study will gather further
useful information related to the long- term use of Recorlev.
Recorlev received orphan drug designation from the FDA and the
European Medicines Agency for the treatment of endogenous Cushing's
syndrome.
Indication & Important Safety Information for
Recorlev®
BOXED WARNING: HEPATOTOXICITY AND QT PROLONGATION
HEPATOTOXICITY
Cases of hepatotoxicity with fatal outcome or requiring liver
transplantation have been reported with oral ketoconazole. Some
patients had no obvious risk factors for liver disease. Recorlev is
associated with serious hepatotoxicity. Evaluate liver enzymes
prior to and during treatment.
QT PROLONGATION
Recorlev is associated with dose-related QT interval
prolongation. QT interval prolongation may result in
life-threatening ventricular dysrhythmias such as torsades de
pointes. Perform ECG and correct hypokalemia and hypomagnesemia
prior to and during treatment.
INDICATION
Recorlev is a cortisol synthesis inhibitor indicated for the
treatment of endogenous hypercortisolemia in adult patients with
Cushing’s syndrome for whom surgery is not an option or has not
been curative.
Limitations of Use
Recorlev is not approved for the treatment of fungal
infections.
CONTRAINDICATIONS
- Cirrhosis, acute liver disease or poorly controlled chronic
liver disease, baseline AST or ALT > 3 times the upper limit of
normal, recurrent symptomatic cholelithiasis, a prior history of
drug induced liver injury due to ketoconazole or any azole
antifungal therapy that required discontinuation of treatment, or
extensive metastatic liver disease.
- Taking drugs that cause QT prolongation associated with
ventricular arrhythmias, including torsades de pointes.
- Prolonged QTcF interval > 470 msec at baseline, history of
torsades de pointes, ventricular tachycardia, ventricular
fibrillation, or prolonged QT syndrome.
- Known hypersensitivity to levoketoconazole, ketoconazole or any
excipient in Recorlev.
- Taking certain drugs that are sensitive substrates of CYP3A4 or
CYP3A4 and P-gp.
WARNINGS AND PRECAUTIONS
Hepatotoxicity
Serious hepatotoxicity has been reported in patients receiving
Recorlev, irrespective of the dosages used or the treatment
duration. Drug-induced liver injury (peak ALT or AST greater than 3
times upper limit of normal) occurred in patients using Recorlev.
Avoid concomitant use of Recorlev with hepatotoxic drugs. Advise
patient to avoid excessive alcohol consumption while on treatment
with Recorlev. Routinely monitor liver enzymes and bilirubin during
treatment.
QT Prolongation
Use Recorlev with caution in patients with other risk factors
for QT prolongation, such as congestive heart failure,
bradyarrhythmias, and uncorrected electrolyte abnormalities, with
more frequent ECG monitoring considered. Routinely monitor ECG and
blood potassium and magnesium levels during treatment.
Hypocortisolism
Recorlev lowers cortisol levels and may lead to hypocortisolism
with a potential for life-threatening adrenal insufficiency.
Lowering of cortisol levels can cause nausea, vomiting, fatigue,
abdominal pain, loss of appetite, and dizziness. Significant
lowering of serum cortisol levels may result in adrenal
insufficiency that can be manifested by hypotension, abnormal
electrolyte levels, and hypoglycemia. Routinely monitor 24-hour
urine free cortisol, morning serum or plasma cortisol, and
patient’s signs and symptoms for hypocortisolism during
treatment.
Hypersensitivity Reactions
Hypersensitivity to Recorlev has been reported. Anaphylaxis and
other hypersensitivity reactions including urticaria have been
reported with oral ketoconazole.
Risks Related to Decreased
Testosterone
Recorlev may lower serum testosterone in men and women.
Potential clinical manifestations of decreased testosterone
concentrations in men may include gynecomastia, impotence, and
oligospermia. Potential clinical manifestations of decreased
testosterone concentrations in women include decreased libido and
mood changes.
ADVERSE REACTIONS
Most common adverse reactions (incidence > 20%) are
nausea/vomiting, hypokalemia, hemorrhage/contusion, systemic
hypertension, headache, hepatic injury, abnormal uterine bleeding,
erythema, fatigue, abdominal pain/dyspepsia, arthritis, upper
respiratory infection, myalgia, arrhythmia, back pain,
insomnia/sleep disturbances, and peripheral edema.
DRUG INTERACTIONS
- Consult approved product labeling for drugs that are substrates
of CYP3A4, P-gp, OCT2, and MATE prior to initiating Recorlev.
- Sensitive CYP3A4 or CYP3A4 and P-gp
Substrates: Concomitant use of Recorlev with these
substrates is contraindicated or not recommended.
- Atorvastatin: Use lowest
atorvastatin dose possible and monitor for adverse reactions for
dosages exceeding 20 mg daily.
- Metformin: Monitor glycemia,
kidney function, and vitamin B12 and adjust metformin dosage as
needed.
- Strong CYP3A4 Inhibitors or
Inducers: Avoid use of these drugs 2 weeks before and during
Recorlev treatment.
- Gastric Acid Modulators: See Full
Prescribing Information for recommendations regarding concomitant
use with Recorlev.
USE IN SPECIFIC POPULATIONS
Lactation: Advise not to breastfeed
during treatment and for one day after final dose.
To report SUSPECTED ADVERSE REACTIONS, contact Xeris
Pharmaceuticals, Inc. at 1-877-937-4737 or FDA at 1-800-FDA-1088 or
www.fda.gov/medwatch.
Please see Full Prescribing
Information, including Boxed Warning.
About Xeris
Xeris (Nasdaq: XERS) is a biopharmaceutical company developing
and commercializing unique therapies for patient populations in
endocrinology, neurology, and gastroenterology. Xeris has three
commercially available products; Gvoke®, a ready-to-use liquid
glucagon for the treatment of severe hypoglycemia, Keveyis®, the
first and only FDA-approved therapy for primary periodic paralysis,
and Recorlev® for the treatment of endogenous Cushing’s syndrome.
Xeris also has a robust pipeline of development programs to extend
the current marketed products into important new indications and
uses and bring new products forward using its proprietary
formulation technology platforms, XeriSol™ and XeriJect™,
supporting long-term product development and commercial
success.
Xeris Biopharma Holdings is headquartered in Chicago, IL. For
more information, visit www.xerispharma.com, or follow us on
Twitter, LinkedIn, or Instagram.
Forward-Looking Statements
Any statements in this press release about future expectations,
plans and prospects for Xeris Biopharma Holdings, Inc. including
statements regarding the market and therapeutic potential of its
products and product candidates, expectations regarding the
long-term use of Recorlev, and other statements containing the
words “will,” “would,” “continue,” and similar expressions,
constitute forward-looking statements within the meaning of The
Private Securities Litigation Reform Act of 1995. These
forward-looking statements are subject to risks and uncertainties
that may cause actual results to differ materially from those
indicated in the forward-looking statements. Such risks and
uncertainties include, but are not limited to, reliance on
third-party suppliers for Gvoke®, Ogluo®, Keveyis®, and Recorlev®
the regulatory approval of its product candidates, its ability to
market and sell its products, failure to realize the expected
benefits of the acquisition, failure to promptly and effectively
integrate Strongbridge’s businesses, general economic and business
conditions that affect the combined company following the
consummation of the acquisition, the impact of the COVID-19
pandemic on the combined company following the consummation of the
transaction, changes in global, political, economic, business,
competitive, market and regulatory forces, future exchange and
interest rates, changes in tax laws, regulations, rates and
policies, future business acquisitions or disposals and competitive
developments and the other risks described in our Quarterly Report
on Form 10-Q and other reports we file from time to time with the
SEC. These forward-looking statements are based on numerous
assumptions and assessments made in light of Xeris’ experience and
perception of historical trends, current conditions, business
strategies, operating environment, future developments, and other
factors it believes appropriate. By their nature, forward-looking
statements involve known and unknown risks and uncertainties
because they relate to events and depend on circumstances that will
occur in the future. The factors described in the context of such
forward-looking statements in this communication could cause Xeris’
plans with respect to Strongbridge, Xeris’ plans with respect to
its products and product candidates, Xeris’ actual results,
performance or achievements, industry results and developments to
differ materially from those expressed in or implied by such
forward-looking statements. Although it is believed that the
expectations reflected in such forward-looking statements are
reasonable, no assurance can be given that such expectations will
prove to have been correct and persons reading this communication
are therefore cautioned not to place undue reliance on these
forward-looking statements which speak only as at the date of this
communication. Additional information about economic, competitive,
governmental, technological, and other factors that may affect
Xeris is set forth in Item 1A, “Risk Factors,” in Xeris’ 2020
Annual Report on Form 10-K, which has been filed with the SEC and
other important factors in Xeris’ subsequent filings with the SEC,
the contents of which are not incorporated by reference into, nor
do they form part of, this communication. Additional information
about economic, competitive, governmental, technological, and other
factors that may affect Strongbridge is set forth in Item 1A, “Risk
Factors,” in Strongbridge’s 2020 Annual Report on Form 10-K, which
has been filed with the SEC, the contents of which are not
incorporated by reference into, nor do they form part of, this
communication. Any forward-looking statements in this communication
are based upon information available to Xeris, as of the date of
this communication and, while believed to be true when made, may
ultimately prove to be incorrect. Subject to any obligations under
applicable law, Xeris does not undertake any obligation to update
any forward- looking statement whether as a result of new
information, future developments or otherwise, or to conform any
forward-looking statement to actual results, future events, or to
changes in expectations. All subsequent written and oral
forward-looking statements attributable to Xeris or any person
acting on behalf of any of them are expressly qualified in their
entirety by this paragraph.
1. Recorlev [prescribing information]. Chicago, IL: Xeris
Pharmaceuticals, Inc.; 2021. 2. Fleseriu M, et al. Lancet Diabetes
Endocrinol. 2019;7(11):855-865. 3. Pivonello R et al. Lancet
Diabetes Endocrinol. 2016; 4: 611-29. 4. Plotz CM, et al. Am J Med.
1952 November;13(5):597-614.
Recorlev®, Xeris Pharmaceuticals®, Xeris CareConnectionTM,
Keveyis®, Gvoke®, and Ogluo® are trademarks owned by or licensed to
Xeris Pharmaceuticals, Inc. All other trademarks referenced herein
are the property of their respective owners. All rights
reserved.
Copyright © 2021. Xeris Pharmaceuticals, Inc. All rights
reserved. US-PR-21-00006 12/21
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version on businesswire.com: https://www.businesswire.com/news/home/20220512005288/en/
Allison Wey Senior Vice President, Investor Relations and
Corporate Communications awey@xerispharma.com (312) 736-1237
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