Madrigal Pharmaceuticals Provides Corporate Updates and Reports First Quarter 2023 Financial Results
- Resmetirom new drug application (NDA) filing on track for Q2 2023
- Resmetirom has received Breakthrough Therapy designation from FDA
- Multiple resmetirom abstracts accepted for presentation at EASL, including primary results and additional data from the Phase 3 MAESTRO-NASH trial
Recent Corporate Highlights
- Madrigal announced that resmetirom has received Breakthrough Therapy designation from the FDA for the treatment of patients with NASH with liver fibrosis. 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.
- The MAESTRO-NASH registrational trial in noncirrhotic NASH has completed enrollment.
- Patient recruitment remains focused on MAESTRO-NASH-OUTCOMES, a noninvasive Phase 3 clinical outcome trial evaluating resmetirom in patients with well-compensated NASH cirrhosis with goals to support an additional indication in NASH cirrhosis and support long-term clinical benefit and full approval for noncirrhotic NASH.
Institute for Clinical and Economic Review(ICER) published an updated Evidence Report for its value assessment of resmetirom and obeticholic acid. The Evidence Report indicates that resmetirom has the potential to be a cost-effective treatment for patients with at-risk NASH.
Resmetirom Data Presentations at EASL
Multiple resmetirom abstracts have been accepted at EASL’s
- Oral presentation: “Primary results from MAESTRO-NASH a pivotal phase 3 52-week serial liver biopsy study in 966 patients with NASH and fibrosis” [
Thursday, June 22at 10:30 AM. Presenter: Stephen Harrison]
- Poster: “Characterizing the histologic implications of resmetirom-induced liver volume reduction using artificial intelligence-powered digital pathology” [Presenter:
- Poster: “Resmetirom helps regulate thyroid hormone levels within the liver in patients with nonalcoholic fatty liver disease” [Presenter:
- Poster: “Resmetirom improves the lipid/lipoprotein profile in patients with nonalcoholic fatty liver disease” [Presenter:
- Poster: “Imaging and biomarker thresholds to accurately diagnose NASH cirrhosis in a 180 patient biopsy confirmed cohort” [Presenter:
NASH Epidemiology and Health Economics Outcomes Research Presentations at ISPOR
Five Madrigal posters focused on NASH epidemiology and health economics outcomes research are being presented at the ISPOR 2023 meeting taking place this week (
- “NASH Progression Rates Based on Fibrosis and Inflammation (NAS): A Paired Biopsy Analysis from a Natural History Cohort in the US” [Presenter:
- “The Impact of Treatment-related Changes in Lipids on the Cost-effectiveness of Resmetirom and Obeticholic Acid for Treatment of Nonalcoholic Steatohepatitis” [Presenter:
- “Impact of Different Non-invasive Tests on Estimated Prevalence of Presumed Nonalcoholic Steatohepatitis Among US Adults, NHANES 2017-2020” [Presenter:
- “Systematic Literature Review, Network Meta-analysis, and Cost-effectiveness Analysis of Resmetirom for the Treatment of Nonalcoholic Steatohepatitis” [Presenter:
- “Primary Cardiovascular Event Risk Associated With Nonalcoholic Steatohepatitis Among US Adults, NHANES 2017-2020” [Presenter:
Financial Results for the Three Months Ended
Operating expenses were
Research and development expenses for the three month period ended
General and administrative expenses for the three month period ended
Interest income for the three month period ended
Interest expense for the three month period ended
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
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
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.
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
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
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,” “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 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
|Condensed Consolidated Statements of Operations|
|(in thousands, except share and per share amounts)|
|Three Months Ended|
|Research and development||62,154||47,929|
|General and administrative||16,182||9,658|
|Total operating expenses||78,336||57,587|
|Loss from operations||(78,336||)||(57,587||)|
|Interest income, net||3,776||69|
|Basic and diluted net loss per common share||$||(4.23||)||$||(3.36||)|
|Basic and diluted weighted average number of common shares outstanding||18,187,924||17,103,395|
|Condensed Consolidated Balance Sheets|
|Cash, cash equivalents and marketable securities||$||329,477||$||358,774|
|Other current assets||1,807||2,595|
|Other non-current assets||1,165||1,203|
|Liabilities and Equity|
|Total liabilities and stockholders’ equity||$||332,449||$||362,572|
Source: Madrigal Pharmaceuticals, Inc.