Madrigal Pharmaceuticals, Inc. (NASDAQ:MDGL), a clinical-stage
biopharmaceutical company pursuing novel therapeutics for
nonalcoholic steatohepatitis (NASH), today announced that
resmetirom has received Breakthrough Therapy designation from the
U.S. Food and Drug Administration (FDA) for the treatment of
patients with NASH with liver fibrosis. The Company also announced
that the outcomes portion of the Phase 3 MAESTRO-NASH biopsy trial
has completed enrollment.
Paul Friedman, M.D., Chief Executive Officer of Madrigal,
stated, “The Breakthrough Therapy designation for resmetirom
reflects the FDA’s recognition of resmetirom's potential in the
treatment of NASH as a serious, life-threatening condition and an
important area of investigational drug development. It also
reinforces our confidence in our regulatory strategy as we approach
the new drug application (NDA) filing for resmetirom, which remains
on track for Q2 2023. The filing is supported by the positive
outcomes on reduction of liver fibrosis and resolution of NASH from
the 52-week serial liver biopsy portion of MAESTRO-NASH.”
Becky Taub, M.D., Chief Medical Officer and President of
Research & Development of Madrigal, stated, "We are also
pleased to announce that the MAESTRO-NASH trial in noncirrhotic
NASH is now fully enrolled. Enrollment of the MAESTRO-NASH study
was closed at approximately 1,750 patients based on the enrollment
target of the 54-month long-term clinical outcome portion of the
study. Patient recruitment remains focused on
MAESTRO-NASH-OUTCOMES, a Phase 3 clinical outcome trial evaluating
resmetirom in patients with well-compensated NASH cirrhosis that
provides a second and potentially earlier opportunity to support
full approval for both noncirrhotic and cirrhotic NASH. Madrigal’s
two Phase 3 outcomes studies are central to our regulatory strategy
and underscore our commitment to verifying clinical benefit of
resmetirom. On behalf of the Madrigal team, I’d like to thank all
the patients, investigators and study sites that are participating
in our ongoing trials.”
Breakthrough Therapy designation is a process intended to
expedite the development and review of drugs for serious or
life-threatening conditions. The criteria for breakthrough therapy
designation require preliminary clinical evidence that demonstrates
the drug may have substantial improvement on at least one
clinically significant endpoint over available therapy, or over
placebo if there is no available therapy. A drug that receives
Breakthrough Therapy designation is eligible for more intensive
guidance on an efficient drug development program and
organizational commitment involving senior managers from FDA.
About the Resmetirom Phase 3 Registration Program for
the Treatment of NASH
Madrigal is currently conducting four Phase 3 clinical trials to
demonstrate the safety and efficacy of resmetirom for the treatment
of NASH: MAESTRO-NASH, MAESTRO-NAFLD-1, MAESTRO-NAFLD-OLE, and
MAESTRO-NASH-OUTCOMES.
MAESTRO-NASH is a multicenter, randomized, double-blind,
placebo-controlled Phase 3 study of resmetirom in patients with
liver biopsy-confirmed NASH and was initiated in March 2019. The
subpart H portion of the study enrolled more than 1,000 patients
with biopsy-proven NASH (at least half with F3 (advanced) fibrosis,
the remainder F2 or F1B (moderate fibrosis) with a few earlier F1
patients, randomized 1:1:1 to receive once-daily resmetirom 80 mg,
resmetirom 100 mg, or placebo. After 52 weeks of treatment, a
second liver biopsy is performed. The dual primary surrogate
endpoints on biopsy were NASH resolution with ≥2-point reduction in
NAS (NAFLD Activity Score), and with no worsening of fibrosis OR a
1-point decrease in fibrosis with no worsening of NAS. Achievement
of either primary endpoint was considered a successful trial
outcome. A key secondary endpoint was lowering of LDL-C.
Patients enrolled in the MAESTRO-NASH study (approximately
1,750) continue on therapy after the initial 52-week treatment
period for up to 54 months to accrue and measure hepatic clinical
outcome events including progression to cirrhosis on biopsy (52
weeks and 54 months) and hepatic decompensation events, as well as
all-cause mortality.
MAESTRO-NAFLD-1 was initiated in December 2019 and the 52-week
multicenter, randomized, placebo-controlled Phase 3 study of
resmetirom in over 1,200 patients with NAFLD, presumed NASH, has
completed the double-blind arms and an open-label 100 mg arm. An
additional open-label active treatment arm in patients with early
(well-compensated) NASH cirrhosis is ongoing. The primary endpoint
was to evaluate the safety and tolerability of resmetirom. A
separate 52 week Phase 3 clinical trial, an open-label extension
study of MAESTRO-NAFLD-1 (MAESTRO-NAFLD-OLE), is ongoing.
Patients in the 52-week Phase 3 MAESTRO-NAFLD-1 study were
randomized 1:1:1:1 to receive once-daily resmetirom 80 mg,
resmetirom 100 mg, placebo in double-blind arms or resmetirom 100
mg in an open-label arm. MAESTRO-NAFLD-1 (unlike MAESTRO-NASH), did
not include a liver biopsy and represents a “real-life” NASH study.
Patients with 3 metabolic risk factors were documented with NASH or
NAFLD by historical liver biopsy or noninvasive techniques. Using
noninvasive measures, MAESTRO-NAFLD-1 was designed to provide
incremental safety information to support the NASH indication as
well as provide additional data regarding clinically relevant key
secondary efficacy endpoints to better characterize the potential
clinical benefits of resmetirom on cardiovascular- and
liver-related endpoints. The primary safety endpoint and several
key secondary endpoints were met, including LDL-C, apolipoprotein
B, and triglyceride lowering and reduction of liver fat as
determined by MRI-PDFF. Additional secondary and exploratory
endpoints were assessed including reduction in liver enzymes,
FibroScan, and MRE scores, and other NASH biomarkers.
Data from the 52-week first 1,000 patient portion of
MAESTRO-NASH, together with data from MAESTRO-NAFLD-1,
MAESTRO-NAFLD-OLE, Phase 2 and Phase 1 data, including safety
parameters, will form the basis for a planned subpart H submission
to FDA for accelerated approval of resmetirom for treatment of
NASH.
In August 2022, Madrigal initiated MAESTRO-NASH-OUTCOMES, a
randomized double-blind placebo-controlled study in approximately
700 patients with early NASH cirrhosis to allow for noninvasive
monitoring of progression to liver decompensation events. A
positive outcome is expected to support the full approval of
resmetirom for noncirrhotic NASH, potentially accelerating the
timeline to full approval. In addition, this study has the
potential to support an additional indication for resmetirom in
patients with well-compensated NASH cirrhosis.
About NASH
Nonalcoholic steatohepatitis (NASH) is a more advanced form of
nonalcoholic fatty liver disease (NAFLD). NAFLD is estimated to
afflict more than 20% of adults globally, about 30% in the United
States. Of that population, 20% may have NASH.
NASH is a leading cause of liver related mortality and an
increasing burden on healthcare systems globally. Additionally,
patients with NASH, especially those with more advanced metabolic
risk factors (hypertension, concomitant type 2 diabetes), are at
increased risk for adverse cardiovascular events and increased
morbidity and mortality.
Once NASH progresses to significant liver fibrosis (stages F2
and F3) the risk of adverse liver outcomes increases dramatically.
NASH is rapidly becoming the leading cause of liver transplantation
in the U.S. There are currently no FDA-approved therapies available
for the treatment of NASH.
About Madrigal Pharmaceuticals
Madrigal Pharmaceuticals, Inc. (Nasdaq: MDGL) is a
clinical-stage biopharmaceutical company pursuing novel
therapeutics for nonalcoholic steatohepatitis (NASH), a liver
disease with high unmet medical need. Madrigal’s lead candidate,
resmetirom, is a once daily, oral, thyroid hormone receptor (THR)-β
selective agonist designed to target key underlying causes of NASH
in the liver. For more information, visit
www.madrigalpharma.com.
Forward Looking Statements
This communication includes “forward-looking statements” made
pursuant to the safe harbor provisions of the Private Securities
Litigation Reform Act of 1995, that are based on Madrigal’s beliefs
and assumptions and on information currently available to it, but
are subject to factors beyond its control. Forward-looking
statements reflect management’s current knowledge, assumptions,
judgment and expectations regarding future performance or events.
Forward-looking statements include: all statements that are not
historical facts; statements referenced by forward-looking
statement identifiers, including the examples in the paragraph
below; resmetirom’s potential to be a cost-effective specialty
therapy for NASH patients with significant liver fibrosis; and
statements or references concerning - the potential efficacy and
safety of resmetirom for noncirrhotic NASH patients and cirrhotic
NASH patients, possible or assumed future results of operations and
expenses, business strategies and plans (including ex-US.
Launch/partnering plans), research and development activities, and
the timing and results associated with the future development of
resmetirom, the timing and completion of projected future clinical
milestone events, including enrollment, additional studies,
top-line data and open label projections, plans, objectives, timing
and support for making for making a Subpart H (Accelerated Approval
of New Drugs for Serious or Life-Threatening Illnesses) submission
to FDA, projections or objectives for obtaining accelerated or full
approval for resmetirom, Madrigal’s primary and key secondary study
endpoints for resmetirom and the potential for achieving such
endpoints and projections, the potential to support an additional
indication for resmetirom in patients with well-compensated NASH
cirrhosis, optimal dosing levels for resmetirom and projections
regarding potential NASH or NAFLD and potential patient benefits
with resmetirom, including future NASH resolution, safety, fibrosis
treatment, cardiovascular effects, lipid treatment, and/or
biomarker effects with resmetirom.
Forward-looking statements can be identified by terms such as
“accelerate,” “achieve,” “allow,” “anticipates,” “appear,” “be,”
“believes,” “can,” “continue,” “could,” “demonstrates,” ”design,”
“estimates,” “expectation,” “expects,” “forecasts,” “future,”
“goal,” “help,” “hopeful,” “inform,” “intended,” “intends,” “may,”
“might,” “on track,” “planned,” “planning,” “plans,” “positions,”
“potential,” “powers,” “predicts,” ”predictive,” “projects,”
“seeks,” “should,” “will,” “will achieve,” “will be,” “would” or
similar expressions and the negatives of those terms.
Forward-looking statements are subject to a number of risks and
uncertainties including, but not limited to: the assumptions
underlying the forward-looking statements; risks of obtaining and
maintaining regulatory approvals, including, but not limited to,
potential regulatory delays or rejections; risks associated with
meeting the objectives of Madrigal’s clinical studies, including,
but not limited to Madrigal’s ability to achieve enrollment
objectives concerning patient numbers (including an adequate safety
database), outcomes objectives and/or timing objectives for
Madrigal’s studies; any delays or failures in enrollment, and the
occurrence of adverse safety events; risks related to the effects
of resmetirom’s mechanism of action; the achievement of enrollment
objectives concerning patient number, safety database and/or timing
for Madrigal’s studies; enrollment and trial conclusion
uncertainties, generally and in relation to COVID-19 related
measures and individual precautionary measures that may be
implemented or continued for an uncertain period of time; market
demand for and acceptance of our products; the potential inability
to raise sufficient capital to fund ongoing operations as currently
planned or to obtain financings on terms similar to those arranged
in the past; the ability to service indebtedness and otherwise
comply with debt covenants; outcomes or trends from competitive
studies; future topline data timing or results; the risks of
achieving potential benefits in studies that includes substantially
more patients, and patients with different disease states, than
prior studies; the timing and outcomes of clinical studies of
resmetirom; and the uncertainties inherent in clinical testing.
Undue reliance should not be placed on forward-looking statements,
which speak only as of the date they are made. Madrigal undertakes
no obligation to update any forward-looking statements to reflect
new information, events or circumstances after the date they are
made, or to reflect the occurrence of unanticipated events. Please
refer to Madrigal’s submissions filed with the U.S. Securities and
Exchange Commission, or SEC, for more detailed information
regarding these risks and uncertainties and other factors that may
cause actual results to differ materially from those expressed or
implied. Madrigal specifically discusses these risks and
uncertainties in greater detail in the section appearing in Part I,
Item 1A of its Annual Report on Form 10-K for the year ended
December 31, 2022, filed with the SEC on February 23, 2023, as
updated, as well as other updates from time to time by Madrigal’s
other filings with the SEC.
Investor Contact Alex Howarth, Madrigal
Pharmaceuticals, Inc., IR@madrigalpharma.com
Media ContactChristopher Frates, Madrigal
Pharmaceuticals, Inc., media@madrigalpharma.com
Madrigal Pharmaceuticals (NASDAQ:MDGL)
Gráfico Histórico do Ativo
De Mar 2024 até Abr 2024
Madrigal Pharmaceuticals (NASDAQ:MDGL)
Gráfico Histórico do Ativo
De Abr 2023 até Abr 2024