FDA approval supported by positive results from
the pivotal Phase 3 SONICS and LOGICS studies demonstrating
Recorlev to be a safe and effective therapeutic option in the
treatment of Cushing's syndrome
FDA decision follows successful completion of
acquisition of Strongbridge Biopharma on October 5, 2021
Post-acquisition, the Company is
well-positioned to address the needs of Cushing’s syndrome patients
in the U.S. who are treated with prescription therapy
Commercial launch of Recorlev is planned for Q1
2022
Xeris Biopharma Holdings, Inc. (Nasdaq: XERS), a
biopharmaceutical company developing and commercializing unique
therapies for patient populations in endocrinology, neurology, and
gastroenterology, today announced the U.S. Food and Drug
Administration (FDA) approval of Recorlev® (levoketoconazole) 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
“We are thrilled with the FDA's approval of Recorlev as a safe
and effective treatment option for patients with endogenous
Cushing's syndrome. With this approval, Xeris’ experienced
endocrinology-focused commercial organization can begin rapidly
working to help address the needs of Cushing’s syndrome patients in
the U.S. who are treated with prescription therapy,” said Paul R.
Edick, Chairman and CEO of Xeris Biopharma. “Today’s announcement
also reinforces the value that we saw in acquiring Strongbridge
Biopharma’s attractive rare disease portfolio, which we believe
will deliver compelling long-term value to our shareholders. We
look forward to making Recorlev commercially available in the first
quarter.”
The approval of Recorlev was based upon safety and efficacy data
from two positive Phase 3 studies that evaluated a combined study
population of 166 patients, which was representative of the adult
drug-treated U.S. population with Cushing’s syndrome.1 The SONICS
study met its primary and key secondary endpoints, significantly
reducing and normalizing mean urinary free cortisol concentrations
without a dose increase (detailed results here).1,2 LOGICS,
a double-blind, placebo-controlled randomized-withdrawal study that
met its primary and key secondary endpoints, confirmed the efficacy
and safety of Recorlev in normalizing and maintaining therapeutic
response compared with placebo (detailed results here).1
“Levoketoconazole (Recorlev) is an important and welcome new
therapeutic option for clinicians to help manage patients with
endogenous Cushing's syndrome, a severe, potentially
life-threatening rare disease, if not appropriately treated, with
multisystem signs and symptoms,” said Maria Fleseriu, M.D., FACE,
professor of Medicine and Neurological Surgery and director of the
Pituitary Center at Oregon Health Sciences University. “In
prospective clinical studies, treatment with levoketoconazole was
shown to be effective for reducing and normalizing cortisol.”
“Cushing’s syndrome is a rare disease that can be physically and
emotionally devastating to the patient. Most patients endure years
of symptoms prior to obtaining a diagnosis and are then faced with
limited effective treatment options," said Leslie Edwin, president
of the Cushing’s Support & Research Foundation. “Today we are
excited to see that the long and complicated path of rare drug
development has reached FDA approval on a new therapeutic option
for our underserved Cushing's community. We are grateful that the
researchers worked so diligently for so long to establish the
safety and efficacy of this drug. Rare disease patients know the
importance of sharing their complicated experiences as ‘expert
witnesses’, and we thank Xeris for being an early adherent to this
concept. We especially want to thank the clinical trial patients
who made this progress possible.”
Xeris is committed to ensuring everyone who needs access to
their therapies will receive it. Xeris has created Xeris
CareConnection™ to provide a comprehensive program for patients and
their caregivers throughout the treatment journey, including
financial assistance, one-on-one support, and educational
resources. Xeris CareConnection also supports healthcare
professionals and their teams through education on access and
reimbursement. To get started with Recorlev, reach out to Xeris
CareConnection (available Monday–Friday from 8 a.m–7 p.m ET) at
1-844-444-RCLV (7258).
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 arrythmias, 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,
bradyarrythmias, 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 Biopharma
Xeris (Nasdaq: XERS) is a biopharmaceutical company developing
and commercializing unique therapies for patient populations in
endocrinology, neurology, and gastroenterology. Xeris has two
commercially available products; Gvoke®, a ready-to-use liquid
glucagon for the treatment of severe hypoglycemia, and Keveyis®,
the first and only FDA-approved therapy for primary periodic
paralysis. In addition to 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 timing
of the commercial launch of Recorlev, estimates and projections
about the potential benefits of the Strongbridge Biopharma
acquisition, the future performance of the combined company and
estimated synergies, the timing or likelihood of expansion into
additional markets 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/20211230005308/en/
Investor Contact Allison Wey Senior Vice President,
Investor Relations and Corporate Communications
awey@xerispharma.com (312) 736-1237
Media Contact Lindsay Rocco Elixir Health PR
lrocco@elixirhealthpr.com (862) 596-1304
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