- Late-breaking knowledge from the double-blind portion of the noninvasive Section 3 MAESTRO NAFLD-1 research present resmetirom to be protected and well-tolerated and to scale back liver fats, fibrosis measures on FibroScan and MRE, and liver enzymes, in addition to a number of atherogenic lipids
- In NASH sufferers with well-compensated cirrhosis, resmetirom:
- was protected and nicely tolerated
- lowered liver fats, LDL-C, and different atherogenic lipids
- lowered noninvasive measures of liver fibrosis and liver enzymes
- lowered liver quantity by a median of ~20{aaa84efcd05d20dc7d0e48929bb8fd8c8895020217096fb46d833d790411cbb9} and in addition lowered spleen quantity
- Firm to host an investor occasion and webcast to evaluation the brand new resmetirom knowledge at 8:00 PM BST / 3:00 PM ET
CONSHOHOCKEN, Pa., June 25, 2022 (GLOBE NEWSWIRE) — Madrigal Prescription drugs, Inc. (NASDAQ:MDGL), a clinical-stage biopharmaceutical firm pursuing novel therapeutics for nonalcoholic steatohepatitis (NASH), as we speak introduced knowledge from a number of resmetirom abstracts offered on the European Affiliation for the Examine of the Liver’s Worldwide Liver Congress (EASL 2022), together with a late-breaking presentation of knowledge from the Section 3 MAESTRO-NAFLD-1 research and three further oral displays from the resmetirom medical improvement program.
Paul Friedman, M.D., Chief Govt Officer of Madrigal, said, “As we speak’s late-breaking presentation at EASL is our first alternative to share the double-blind outcomes from the MAESTRO-NAFLD-1 security research in a serious scientific assembly. The information from this research will play an necessary position within the deliberate new drug utility submission for resmetirom and assist form the noninvasive testing methods that information affected person care in ‘actual world’ medical apply.”
Becky Taub, M.D., Chief Medical Officer and President of Analysis & Growth of Madrigal, added, “Along with the late-breaker, we’re sharing new security and efficacy knowledge from sufferers with compensated NASH cirrhosis who participated in an open-label portion of MAESTRO NAFLD-1; these knowledge knowledgeable our choice to provoke a brand new Section 3 outcomes research on this extra superior NASH affected person inhabitants.”
Stephen Harrison, M.D., Medical Director for Pinnacle Medical Analysis, San Antonio, Texas, Visiting Professor of Hepatology, Oxford College, and Principal Investigator of the MAESTRO research, commented, “The MAESTRO-NAFLD-1 knowledge we’re presenting at EASL proceed to strengthen confidence within the favorable security profile of resmetirom and supply a deeper view of efficacy in sufferers with each early-to-moderate fibrosis and compensated NASH cirrhosis. The marked reductions in noninvasive measures of fibrosis, liver fats, and liver quantity noticed at 52 weeks within the open-label cirrhosis portion of the trial are notably encouraging; it is a difficult-to-treat inhabitants at elevated danger of progressing to damaging outcomes.”
Late-Breaking Oral Presentation: “Major knowledge analyses of MAESTRO-NAFLD-1, a 52 week double-blind placebo-controlled part 3 medical trial of resmetirom in sufferers with NAFLD” (LB005)
Major and key secondary endpoints from the double-blind, placebo-controlled, 969-patient MAESTRO-NAFLD-1 security research have been achieved; resmetirom was protected and nicely tolerated and offered vital reductions in liver fats (measured utilizing magnetic resonance imaging proton density fraction (MRI-PDFF) and FibroScan managed attenuation parameter (CAP)), LDL-C, and different atherogenic lipids vs placebo.
Sufferers handled with resmetirom additionally achieved vital reductions relative to placebo in ALT, AST, and GGT.
For these sufferers with adequate baseline liver stiffness, as measured by FibroScan vibration-controlled transient elastography (VCTE) or magnetic resonance elastography (MRE), responder analyses confirmed statistically vital VCTE and MRE responses within the resmetirom teams in comparison with placebo.
Opposed event-related withdrawals have been unusual within the MAESTRO-NAFLD-1 research. The most typical opposed occasion reported with larger frequency within the resmetirom teams vs placebo was typically gentle diarrhea or elevated stool frequency originally of remedy.
Oral Presentation: “Biomarkers, imaging and security in a well-compensated NASH cirrhotic cohort handled with resmetirom, a thyroid hormone receptor beta agonist, for 52 weeks” (OS121)
105 sufferers with well-compensated NASH cirrhosis have been enrolled within the open-label arm of the MAESTRO-NAFLD-1 research. Baseline FibroScan VCTE (kPa 24.6) and MRE (5.7) scores have been according to F4 fibrosis. Sufferers with decrease MRI-PDFF (≤5{aaa84efcd05d20dc7d0e48929bb8fd8c8895020217096fb46d833d790411cbb9}) at baseline had extra progressed cirrhosis and larger spleen volumes. Much like sufferers with non-cirrhotic NASH, liver quantity was significantly elevated in comparison with regular at baseline.
Resmetirom lowered MRI-PDFF and LDL-C and different atherogenic lipids in sufferers with NASH cirrhosis and lowered FibroScan managed attenuation parameter (CAP), VCTE, and MRE in a big fraction of sufferers. The biggest discount in FibroScan VCTE (imply discount of 9 kPa) occurred within the extra superior group (baseline PDFF ≤5{aaa84efcd05d20dc7d0e48929bb8fd8c8895020217096fb46d833d790411cbb9}). Comparable enhancements have been noticed in MRE.
73{aaa84efcd05d20dc7d0e48929bb8fd8c8895020217096fb46d833d790411cbb9} of sufferers, unbiased of baseline cirrhosis severity, had not less than 15{aaa84efcd05d20dc7d0e48929bb8fd8c8895020217096fb46d833d790411cbb9} discount in liver quantity at Week 52. Spleen quantity was additionally lowered and was strongly correlated with liver quantity change and publicity to resmetirom.
Reductions in liver enzymes and atherogenic lipids have been related throughout affected person subgroups.
Resmetirom was protected and nicely tolerated. As noticed in sufferers with noncirrhotic NASH, gentle GI opposed occasions have been seen originally of remedy. No variations in security parameters between sufferers with cirrhosis in comparison with noncirrhotic NASH sufferers have been famous. No thyroid axis adjustments or hyper- or hypothyroid signs have been noticed.
Further Oral Displays and Posters on the Worldwide Liver Congress
Abstracts from the resmetirom improvement program present new insights to tell noninvasive testing methods, enhance synthetic intelligence-based analysis of therapy response, and higher characterize the fee burden of NASH.
- Oral presentation: “Utility of FIB-4 thresholds to establish sufferers with at-risk F2-F3 NASH based mostly on screening knowledge from a 2,000 affected person biopsy confirmed cohort of resmetirom Section 3 medical trial, MAESTRO-NASH” (OS101)
- Oral presentation: “Affect of resmetirom-mediated reductions in liver quantity and steatosis in contrast with placebo on the quantification of fibrosis utilizing second harmonic technology in a serial liver biopsy research” (OS030)
- Poster: “Retrospective AI-based measurement of NASH histology (AIM-NASH) evaluation of biopsies from Section 2 research of Resmetirom confirms vital treatment-induced adjustments in histologic options of nonalcoholic steatohepatitis” (SAT094)
- Poster: “The next FIB-4 rating is related to increased healthcare prices and hospitalizations in sufferers with nonalcoholic steatohepatitis” (THU094)
Investor Occasion and Webcast
Madrigal will host an investor occasion in London with webcast on Saturday, June 25 at 8:00 PM BST / 3:00 PM ET. Traders and analysts can click on right here to register for the reside occasion in London. To entry the webcast of the decision with slides please go to the Traders part of Madrigal’s web site or click on right here. An archived webcast shall be accessible on the Madrigal web site after the occasion.
In regards to the Resmetirom Section 3 Registration Program for the Therapy of NASH
Madrigal is at the moment conducting two Section 3 medical trials, MAESTRO-NASH and MAESTRO-NAFLD-1, to reveal the protection and efficacy of resmetirom for the therapy of NASH.
MAESTRO-NASH is a multicenter, randomized, double-blind, placebo-controlled Section 3 research of resmetirom in sufferers with liver biopsy-confirmed NASH and was initiated in March 2019. The research focused enrollment of 900 sufferers with biopsy-proven NASH (fibrosis stage 2 or 3, not less than 450 fibrosis stage 3), randomized 1:1:1 to obtain once-daily resmetirom 80 mg, resmetirom 100 mg, or placebo. After 52 weeks of therapy, a second biopsy is carried out. The twin main surrogate endpoints on biopsy are NASH decision with ≥2-point discount in NAS (NAFLD Exercise Rating), and with no worsening of fibrosis OR a 1-point lower in fibrosis with no worsening of NASH. Both main endpoint will be achieved for a profitable trial end result. A key secondary endpoint is reducing of LDL-C. The deliberate goal enrollment was introduced as accomplished on June 30, 2021.
The primary 900 sufferers within the MAESTRO-NASH research will proceed on remedy after the preliminary 52-week therapy interval; as much as one other 1,100 sufferers are to be added utilizing the identical randomization plan. The research is predicted to proceed for as much as 54 months to accrue and measure hepatic medical end result occasions together with development to cirrhosis on biopsy (52 weeks and 54 months) and hepatic decompensation occasions.
MAESTRO-NAFLD-1 was initiated in December 2019 and the 52-week multicenter, randomized, double-blind, placebo-controlled Section 3 research of resmetirom in over 1,200 sufferers with NAFLD, presumed NASH, has accomplished the double-blind arms and an open-label 100 mg arm. An extra open-label energetic therapy arm in sufferers with early (well-compensated) NASH cirrhosis is ongoing. The first endpoint is to guage the protection and tolerability of resmetirom. An open-label extension research (MAESTRO-NAFLD-OLE) is ongoing.
Sufferers within the 52-week blinded part of MAESTRO-NAFLD-1 have been randomized 1:1:1:1 to obtain once-daily resmetirom 80 mg, resmetirom 100 mg, placebo or a resmetirom 100 mg in an open-label arm. MAESTRO-NAFLD-1 (not like MAESTRO-NASH), didn’t embrace a liver biopsy and represents a “real-life” NASH research. Sufferers with 3 metabolic danger components have been documented with NASH or NAFLD by historic liver biopsy or noninvasive methods. Utilizing noninvasive measures, MAESTRO-NAFLD-1 was designed to supply incremental security info to assist the NASH indication in addition to present further knowledge relating to clinically related key secondary efficacy endpoints to higher characterize the potential medical advantages of resmetirom on cardiovascular- and liver-related endpoints. These key secondary endpoints included LDL-C, apolipoprotein B, and triglyceride reducing; and discount of liver fats as decided by MRI-PDFF. Further secondary and exploratory endpoints have been assessed together with discount in liver enzymes, FibroScan, and MRE scores and different NASH biomarkers.
Information from the 52-week portion of MAESTRO-NASH, along with knowledge from MAESTRO-NAFLD-1 and different knowledge, together with security parameters, will type the premise for a possible subpart H submission to FDA for accelerated approval of resmetirom for therapy of NASH.
In Might 2022, Madrigal introduced plans to develop the resmetirom improvement program by initiating MAESTRO-NASH Outcomes, a randomized double-blind placebo-controlled research in roughly 700 sufferers with early NASH cirrhosis to permit for non-invasive monitoring of development to liver decompensation occasions. A constructive end result is predicted to assist the total approval of resmetirom for noncirrhotic NASH, probably accelerating the timeline to full approval. As well as, this research has the potential to broaden the label for resmetirom to incorporate NASH sufferers with compensated cirrhosis.
About Madrigal Prescription drugs
Madrigal Prescription drugs, Inc. (Nasdaq: MDGL) is a clinical-stage biopharmaceutical firm pursuing novel therapeutics for nonalcoholic steatohepatitis (NASH), a liver illness with excessive unmet medical want. Madrigal’s lead candidate, resmetirom, is a as soon as each day, oral, thyroid hormone receptor (THR)-β selective agonist designed to focus on key underlying causes of NASH within the liver. Resmetirom is at the moment being evaluated in two Section 3 medical research (MAESTRO-NASH and MAESTRO-NAFLD-1) designed to reveal a number of advantages in sufferers with NASH. For extra info, go to www.madrigalpharma.com.
Ahead Wanting Statements
This communication incorporates “forward-looking statements” made pursuant to the protected harbor provisions of the Personal Securities Litigation Reform Act of 1995, which might be based mostly on our beliefs and assumptions and on info at the moment accessible to us however are topic to components past our management. Ahead-looking statements embrace however should not restricted to statements or references regarding: our medical trials, together with the anticipated timing of disclosure, displays of knowledge from, or outcomes from our trials; analysis and improvement actions; market dimension and affected person therapy estimates for NASH and NAFLD sufferers; the timing and outcomes related to the longer term improvement of our lead product candidate, MGL-3196 (resmetirom); our main and secondary research endpoints for resmetirom and the potential for reaching such endpoints and projections; plans, goals and timing for making a Subpart H (Accelerated Approval of New Medication for Severe or Life-Threatening Sicknesses) submission to FDA; projections or goals for acquiring accelerated or full approval for resemtirom for non-cirrhotic NASH sufferers and NASH sufferers with compensated cirrhosis; optimum dosing ranges for resmetirom; projections relating to potential future NASH decision, security, fibrosis therapy, cardiovascular results, lipid therapy and/or biomarker results with resmetirom; the potential efficacy and security of resmetirom for non-cirrhotic NASH sufferers and cirrhotic NASH sufferers; ex-U.S. launch/partnering plans; the predictive energy of liver fats discount, as measured by non-invasive exams, on NASH decision with fibrosis discount or enchancment; the predictive energy of liver fats, liver quantity adjustments or MAST scores for NASH and/or NAFLD sufferers; the results of resmetirom’ s mechanism of motion; the achievement of enrollment goals regarding affected person quantity, security database and/or timing for our research; the predictive energy of NASH decision and/or liver fibrosis discount or enchancment with resmetirom utilizing non-invasive exams, together with the usage of ELF, FibroScan, MRE and/or MRI-PDFF; the power to develop medical proof demonstrating the utility of non-invasive instruments and methods to display screen and diagnose NASH and/or NAFLD sufferers; the predictive energy of non-invasive exams typically, together with for functions of diagnosing NASH, monitoring affected person response to resmetirom, or recruiting a NASH medical trial; potential NASH or NAFLD affected person danger profile advantages with resmetirom; the potential for resmetirom to turn into the best-in-class and/or first-to-market therapy possibility for sufferers with NASH and liver fibrosis; and our doable or assumed future outcomes of operations and bills, enterprise methods and plans, capital wants and financing plans, traits, market sizing, aggressive place, trade setting and potential development alternatives, amongst different issues. Ahead-looking statements: mirror administration’s present data, assumptions, judgment and expectations relating to future efficiency or occasions; embrace all statements that aren’t historic information; and will be recognized by phrases equivalent to “speed up,” “obtain,” “permit,” “anticipates,” “be,” “believes,” “can,” “proceed,” “might,” “reveal,” ”design,” “estimates,” “expectation,” “expects,” “forecasts,” “future,” “aim,” “hopeful,” ”inform,” “intends,” “might,” “would possibly,” “on monitor,” “deliberate”, “planning,” “plans,” “positions,” “potential,” “powers,” “predicts,” ”predictive,” “initiatives,” “seeks,” “ought to,” “will,” “will obtain,” “shall be,” “would” or related expressions and the negatives of these phrases. Though administration presently believes that the expectations mirrored in such forward-looking statements are affordable, it may give no assurance that such expectations will show to be appropriate and you need to be conscious that precise outcomes might differ materially from these contained within the forward- trying statements.
Ahead-looking statements are topic to numerous dangers and uncertainties together with, however not restricted to: our medical improvement of resmetirom; enrollment uncertainties, typically and in relation to COVID-19-related measures which may be continued for an unsure time frame or carried out; outcomes or traits from aggressive research; future topline knowledge timing or outcomes; the dangers of reaching potential advantages in research that embrace considerably extra sufferers, and sufferers with completely different illness states, than our prior research; limitations related to early stage or non-placebo managed research knowledge; the timing and outcomes of medical research of resmetirom; and the uncertainties inherent in medical testing. Undue reliance shouldn’t be positioned on forward- trying statements, which converse solely as of the date they’re made. Madrigal undertakes no obligation to replace any forward-looking statements to mirror new info, occasions or circumstances after the date they’re made, or to mirror the incidence of unanticipated occasions. Please consult with Madrigal’s submissions filed or furnished with the U.S. Securities and Alternate Fee for extra detailed info relating to these dangers and uncertainties and different components which will trigger precise outcomes to vary materially from these expressed or implied. We particularly talk about these dangers and uncertainties in larger element within the part entitled “Threat Elements” in our Annual Report on Type 10-Ok for the yr ended December 31, 2021, our Quarterly Report on type 10-Q for the Quarter ended March 31, 2022, and in our different filings with the SEC.
Investor Contact
Alex Howarth, Madrigal Prescription drugs, Inc., [email protected]
Media Contacts
Christopher Frates, Madrigal Prescription drugs, Inc., [email protected]
