XeriSol™ formulation enabled predictable
bioavailability and sustained levels of levothyroxine in a
once-weekly subcutaneous presentation
Once-weekly SC levothyroxine (XP-8121)
participants normalized TSH/T4 levels using 45% less drug than
would be needed for their daily oral dose on a weekly basis
Data established an average once-weekly SC dose
of XP-8121 and confirmed previous Phase 1 study of a 4X target dose
conversion factor when switching from once-daily oral
administration of levothyroxine
Participants who completed the study rated
higher treatment satisfaction with XP-8121 compared to oral and a
majority (72%) indicated a strong preference for the SC route of
administration
Study exposed the challenges of achieving and
maintaining normal TSH with daily oral levothyroxine therapy
FDA End-of-Phase 2 interaction to facilitate a
Phase 3 pivotal study program is expected by year-end
Xeris Biopharma Holdings, Inc. (Nasdaq: XERS), a growth-oriented
biopharmaceutical company committed to improving patients’ lives by
developing and commercializing innovative products across a range
of therapies, today announced topline results from its recently
completed Phase 2 multi-center, open label, study of XP-8121 for
the treatment of adults with hypothyroidism. XP-8121 employs the
Company’s XeriSol™ formulation technology to enable a novel
once-weekly SC injection of levothyroxine. This novel formulation
significantly increases the bioavailability of levothyroxine
reducing overall drug exposure and enabling a dosing regimen with
the potential to mitigate the many challenges associated with
achieving and maintaining a normal level of thyroid stimulating
hormone (TSH) with daily oral formulations of levothyroxine.
The Phase 2 study (NCT05823012) was a non-randomized,
open-label, single arm, self-controlled study of XP-8121
(levothyroxine sodium) to determine a target dose conversion factor
from stably dosed oral levothyroxine to XP-8121 (levothyroxine
sodium) in 46 patients with hypothyroidism and to assess the safety
and tolerability of XP-8121 (levothyroxine sodium) after
once-weekly SC injections. The Phase 2 study leveraged the
bioavailability observations of a previous Phase 1 study in which
PK analysis showed that participants could achieve comparable
systemic exposure with XP-8121 at only 57% of a weekly oral dose.
The Phase 2 study included the following periods: Screening,
Titration Period (2 to 8 weeks), and Maintenance Period (4 weeks).
Participants entered the study on a stable oral dose (≥ 3 months)
with normal TSH and free T4 laboratory values.
Participants were receiving a daily oral levothyroxine dose of
83.7 ± 31.14 mcg (mean ± SD) at study entry. To ensure the safety
of study participants, once-weekly SC injection of XP-8121 was
initiated at 2X their daily dose and titrated every 2 weeks to a
target of 4X their daily dose. Participants completing the
Maintenance Period were receiving a weekly XP-8121 dose of 324.4 ±
125.59 mcg. The geometric mean ratio of the once-weekly dose of
XP-8121 to the daily dose levothyroxine (aka dose conversion
factor) was 4.02 [90% CI 3.79, 4.27]. A total of 30 participants
(65.2%) experienced at least 1 TEAE (Treatment Emergent Adverse
Event) with most rated mild (87%) and moderate (13%) in severity.
The most frequent (> 2 participants) TEAE included fatigue
(21.7%), injection site pain (10.9%), headache (8.7%) and urinary
tract infection (6.5%). No deaths or other serious adverse events
(SAEs) were reported. Injection site tolerability was assessed with
every SC administration of XP-8121 (> 450 injections). There
were very few reports of discomfort (18%; mostly mild intensity),
erythema (7%; Draize scale) or edema (1%; Draize scale). No
participant discontinued from the study due to an injection site
reaction. The Treatment Satisfaction Questionnaire for Medication
(TSQM-9) was administered to assess patient satisfaction. XP-8121
scored consistently higher in all three domains (effectiveness,
convenience, and global satisfaction) compared to oral
levothyroxine. At the conclusion of the study, participants were
asked to rate preference for once-weekly XP-8121. A majority (72%)
indicated a strong preference for the SC route of administration
based on categorical attributes of convenience (60.6%), ease of
administration (45.5%), frequency of administration (54.5%), level
of compliance (27.3%) and confidence in therapy (36.4%).
“A 2022 study published in the Journal of the Endocrine Society
estimated the prevalence of hypothyroidism in the U.S. grew to
11.7% or approximately 30 million adults in 2019*. Innumerable
reports have been published documenting the various compliance and
absorption challenges that can interfere with the bioavailability
of oral levothyroxine. Interestingly, in our own Phase 2 study, 40%
of patients considered stable at the time of screening were found
to have their TSH or T4 outside of normal range. We believe our
once-weekly SC injection can enable control in patients who
struggle with oral preparations for a variety of reasons,” said
Paul R. Edick, Xeris’ Chairman and CEO.
“We are excited by the initial top line results of our Phase 2
dose-finding study of XP-8121. These results are further evidence
of our target dose conversion and consistent with the estimates
generated from the prior Phase 1 study in healthy volunteers,” said
Kenneth E. Johnson, PharmD, Xeris’ Senior Vice President, Global
Development and Medical Affairs. “Given the known challenges of
oral bioavailability of levothyroxine and further by the high rate
of screen failures observed in our phase 2 study, we believe that
XP-8121 could fill a substantial unmet medical need. We look
forward to meeting with the FDA later this year and expect to
present complete study results at upcoming medical meetings as well
as submission to peer-reviewed medical journals.”
About Hypothyroidism
Hypothyroidism, or underactive thyroid, happens when your
thyroid gland doesn't make enough thyroid hormones to meet your
body's needs. Your thyroid is a small, butterfly-shaped gland in
the front of your neck. It makes hormones that control the way the
body uses energy. These hormones affect nearly every organ in your
body and control many of your body's most important functions. For
example, they affect your breathing, heart rate, weight, digestion,
and moods. Without enough thyroid hormones, many of your body's
functions slow down.
About Levothyroxine
Therapeutically, levothyroxine is administered when the body is
deficient in the endogenous hormone. Administration of
levothyroxine is thus indicated for acquired thyroid disease
(primary hypothyroidism), in cases of decreased secretion of TSH
from the anterior pituitary gland (secondary hypothyroidism), and
in cases of decreased secretion of TRH from the hypothalamus
(tertiary hypothyroidism) and for congenital hypothyroidism. In
most patients, hypothyroidism is a permanent condition requiring
lifelong treatment. The goal of therapy is restoration of the
euthyroid state, which can reverse the clinical manifestations of
hypothyroidism and significantly improve quality of life.
About XeriSol™
The proprietary XeriSol™ non-aqueous formulation technology
platform is designed to address the limitations of aqueous
formulations for peptide and small molecule drugs. The solutions
are formulated using biocompatible, non-aqueous solutions that
impart high stability and solubility to drugs allowing for
development of room temperature stable, ready-to-use formulations.
XeriSol™ formulations have been used extensively in global
commercial products (Gvoke®/Ogluo®) and clinical trials. The
technology is protected by an extensive patent estate, trade
secrets and know-how, and it is available for licensing.
About Xeris
Xeris (Nasdaq: XERS) is a growth-oriented biopharmaceutical
company committed to improving patient lives by developing and
commercializing innovative products across a range of therapies.
Xeris has three commercially available products; Gvoke®, a
ready-to-use liquid glucagon for the treatment of severe
hypoglycemia, Keveyis®, a proven 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 X,
LinkedIn, or Instagram.
Forward-looking Statement
Any statements in this press release other than statements of
historical fact are forward-looking statements. Forward-looking
statements include, but are not limited to, statements about future
expectations, plans and prospects for Xeris Biopharma Holdings,
Inc. including statements regarding expectations for the release of
clinical data or results from clinical trials, the timing of
meetings with regulatory authorities, the market and therapeutic
potential of its products and product candidates, including the
therapeutic potential of XP-8121, the potential utility of its
formulation platforms, including XeriSol™-formulated subcutaneous
levothyroxine’s potential benefits compared to daily oral
formulations, the intellectual property rights associated with
XeriSol™ and its availability for licensing and other statements
containing the words “will,” “would,” “continue,” “expect,”
“should,” “anticipate” and similar expressions, constitute
forward-looking statements within the meaning of The Private
Securities Litigation Reform Act of 1995. 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, geopolitical factors 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 various factors that could cause Xeris’ actual results,
performance or achievements, industry results and developments to
differ materially from those expressed in or implied by such
forward-looking statements, include, but are not limited to, its
financial position and need for financing, including to fund its
product development programs or commercialization efforts, whether
its products will achieve and maintain market acceptance in a
competitive business environment, its reliance on third-party
suppliers, including single-source suppliers, its reliance on third
parties to conduct clinical trials, the ability of its product
candidates to compete successfully with existing and new drugs, and
its and collaborators’ ability to protect its intellectual property
and proprietary technology. No assurance can be given that such
expectations will be realized and persons reading this
communication are, therefore, cautioned not to place undue reliance
on these forward-looking statements. Additional risks and
information about potential impacts of financial, operational,
economic, competitive, regulatory, governmental, technological, and
other factors that may affect Xeris can be found in Xeris’ filings,
including its most recently filed Annual Report on Form 10-K filed
with the Securities and Exchange Commission, the contents of which
are not incorporated by reference into, nor do they form part of,
this communication. Forward-looking statements in this
communication are based on information available to us, as of the
date of this communication and, while we believe our assumptions
are reasonable, actual results may differ materially. Subject to
any obligations under applicable law, we do 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.
- Wyne, Kathleen L., et al. “Hypothyroidism Prevalence in the
United States: A Retrospective Study Combining National Health and
Nutrition Examination Survey and Claims Data, 2009–2019.” Journal
of the Endocrine Society, vol. 7, no. 1, 2023, pp. bvac172–bvac172,
https://doi.org/10.1210/jendso/bvac172
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version on businesswire.com: https://www.businesswire.com/news/home/20240530612890/en/
Investor Contact Allison Wey Senior Vice President,
Investor Relations and Corporate Communications
awey@xerispharma.com
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