Full Press Release Details
Madrigal Pharmaceuticals Provides Corporate Updates and Reports Second Quarter 2023 Financial Results
PA, August 8, 2023 Madrigal Pharmaceuticals, Inc. (NASDAQ:MDGL), a clinical-stage biopharmaceutical company pursuing novel therapeutics for nonalcoholic steatohepatitis (NASH), today provides a summary of recent corporate
accomplishments and reports second quarter 2023 financial results.
Paul Friedman, M.D., Chief Executive Officer of Madrigal, stated, The recent
submission of the resmetirom NDA represents an important milestone for Madrigal and the NASH community. Based on the depth and breadth of efficacy and safety data we have generated through the MAESTRO program, I believe we are well-positioned to
support the FDA s review of resmetirom. In parallel with our regulatory activities, our Commercial and Medical Affairs teams are intently focused on preparing for a potential
first-to-market launch in the U.S.
Becky Taub, M.D., Chief Medical
Officer and President of Research & Development of Madrigal, stated, In addition to the positive biopsy results supporting our regulatory filings in the U.S. and Europe, the MAESTRO program has generated extensive biomarker and
imaging data to help advance noninvasive strategies that may be used in real-world clinical practice to identify appropriate patients for resmetirom and monitor treatment response. The MAESTRO-NASH results were featured in the opening session of the
EASL Congress earlier this summer, and we look forward to presenting additional noninvasive data from the study at future scientific congresses.
Remy Sukhija, Chief Commercial Officer of Madrigal, added, As a once-daily, oral medication that is intended to treat the underlying causes of NASH in
the liver, resmetirom has a unique opportunity to become the foundational therapy for patients with NASH with liver fibrosis. Our conviction in resmetirom s potential is grounded in extensive market research with hepatologists and
gastroenterologists. Based on the efficacy and safety data observed in the MAESTRO-NASH trial, these liver specialist physicians report strong intent-to-prescribe
resmetirom for appropriate patients, if approved.
Mr. Sukhija continued, NASH care pathways are evolving rapidly in anticipation of an
approved treatment, and the new recommendation from the American Diabetes Association to screen for NASH in patients with type 2 diabetes, alongside similar existing recommendations from hepatology and gastroenterology medical societies, should
expand the population of identified patients in need of treatment. Additionally, Madrigal s efforts to improve disease education including the NASH Explored campaign and the new Taking on Fatty Liver and NASH
campaign are gaining momentum and driving engagement with healthcare providers, patients and payers.
Recent Corporate Highlights
Financial Results for the Six Months Ended June 30, 2023
As of June 30, 2023, Madrigal had cash, cash equivalents and marketable securities of $298.4 million, compared to $358.8 million at
December 31, 2022. The decrease in cash and marketable securities resulted primarily from cash used in operations of $159.4 million, partially offset by the capital raised under the Loan Facility ( Loan Facility ) with Hercules
Capital, Inc. ( Hercules ) and our at-the-market sales agreement.
Operating expenses were $86.5 million and $164.8 million for the three month and six month periods ended June 30, 2023, compared to
$70.3 million and $127.9 million in the comparable prior year periods.
Research and development expenses for the three and six month periods
ended June 30, 2023 were $68.6 million and $130.8 million, compared to $58.5 million and $106.4 million in the comparable prior year periods. The increase is attributable primarily to additional activities related to the
Phase 3 clinical trials, and an increase in head count.
General and administrative expenses for the three and six month periods ended June 30, 2023 were
$17.8 million and $34.0 million, compared to $11.8 million and $21.4 million in the comparable prior year periods. The increase is due primarily to increases in commercial preparation activities, including an increase in
headcount and an increase in non-cash stock compensation.
Interest income for the three and six month periods
ended June 30, 2023 was $3.6 million and $7.3 million, compared to $0.3 million and $0.4 million in the comparable prior year periods. The increase in interest income was due primarily to a higher average interest rate in
Interest expense for the three and six month periods ended June 30, 2023 was $2.9 million and $5.2 million, compared to
$0.8 million and $0.8 million in the comparable prior year periods. The increase in interest expense was as a result of the Loan Facility we entered with Hercules.
About the Resmetirom Phase 3 Registration Program for the Treatment of NASH
Resmetirom is a once daily, oral, thyroid hormone receptor (THR)- selective agonist designed to target key
underlying causes of NASH in the liver.
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. The
portion of the study designed to support a subpart H approval enrolled more than 1,000 patients with biopsy-proven NASH with fibrosis, randomized 1:1:1 to receive once-daily resmetirom 80 mg, resmetirom 100 mg, or placebo. 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 after 52 weeks of treatment. Achievement of either primary endpoint was considered a successful trial outcome.
Madrigal announced that both daily oral doses of resmetirom achieved both MAESTRO-NASH primary liver biopsy endpoints. Multiple secondary endpoints were also achieved, including statistically significant reductions by resmetirom as compared with
placebo in atherogenic lipids and lipoproteins, liver enzymes, fibrosis biomarkers, and imaging tests.
Resmetirom was generally safe and well-tolerated
at both the 80 mg and 100 mg doses. Consistent with previous Phase 2 and Phase 3 data, the most common adverse event reported with greater frequency in the resmetirom groups versus placebo was an excess of generally mild and transient diarrhea and
nausea at the beginning of therapy.
Patients enrolled in MAESTRO-NASH (approximately 1,750 total enrollment) 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. This portion of the study is designed to generate confirmatory data that, if positive, will help verify resmetirom s clinical benefit and support full approval.
MAESTRO-NAFLD-1 was a 52-week multicenter, randomized,
placebo-controlled, double-blind Phase 3 study of resmetirom in ~1,200 patients with NAFLD, presumed NASH. MAESTRO-NAFLD-1 might be considered a real-world NASH study in that diagnosis was based on
noninvasive measures rather than liver biopsy. The primary endpoint was to evaluate the safety and tolerability of resmetirom.
Patients in the MAESTRO-NAFLD-1 study were randomized 1:1:1:1 to receive once-daily resmetirom 80 mg, resmetirom 100 mg, or placebo in double-blind arms or resmetirom 100 mg in an open-label arm. 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 of MAESTRO-NAFLD-1 and key secondary endpoints were achieved: resmetirom was safe, well-tolerated and provided statistically significant improvements in LDL-C, apolipoprotein B,
triglycerides, and liver fat as measured by MRI-PDFF.
An additional open-label active treatment arm in 180
patients with early (well-compensated) NASH cirrhosis was conducted. Resmetirom was safe and well tolerated in the MAESTRO-NAFLD-1 open-label cohort of patients with well-compensated NASH cirrhosis. As
observed in patients with noncirrhotic NASH, mild GI adverse events were seen at the beginning of therapy. Resmetirom reduced LDL-C, other atherogenic lipids and lipoproteins, and MRI-PDFF in patients with NASH cirrhosis and also reduced liver and spleen volume.
A separate 52 week Phase 3 clinical
trial, an open-label active treatment extension study of MAESTRO-NAFLD-1 (MAESTRO-NAFLD-OLE), in about 700 patients is ongoing.
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, form the basis for Madrigal s subpart H submission to FDA for accelerated
approval of resmetirom for treatment of NASH with liver fibrosis.
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.
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.
In NASH, thyroid hormone beta activity in the liver is impaired, leading to a reduction in mitochondrial function and
beta-oxidation of fatty acids, which in turn drive inflammation and liver fibrosis.
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
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)- 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 the first specialty therapy for NASH patients with significant liver fibrosis; statements concerning potential accelerated approval; 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, demonstrating clinical benefit to support accelerated approval, 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
Forward-looking statements can be identified by terms such as accelerate, achieve, allow,
anticipates, appear, be, believes, can, confidence, continue, could, demonstrates, design, estimates,
expectation, expects, forecasts, future, goal, help, hopeful, inform, 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