Madrigal Pharmaceuticals Stock

Madrigal Pharmaceuticals, Inc. (Madrigal), a clinical-stage biopharmaceutical company, engages in pursuing novel therapeutics for nonalcoholic steatohepatitis, or NASH.

The company’s lead candidate, resmetirom, is a once-daily, oral, liver-directed thyroid hormone receptor-ß (THR-ß) agonist designed to target key underlying causes of NASH. Madrigal is conducting multiple Phase 3 clinical trials to evaluate the safety and efficacy of resmetirom for the treatment of NASH, including the pivotal MAESTRO-NASH biopsy study in patients with significant fibrosis, the MAESTRO-NASH Outcomes study in patients with NASH with compensated cirrhosis and the MAESTRO-NAFLD-1 safety study. Positive results from the pivotal MAESTRO-NASH biopsy study were published in the New England Journal of Medicine in February 2024.

In September 2023, the U.S. Food and Drug Administration (the FDA) informed Madrigal that it accepted for review its New Drug Application (NDA) for resmetirom for the treatment of adult patients with NASH with liver fibrosis and granted a Priority Review designation. The FDA assigned a Prescription Drug User Fee Act (PDUFA) date of March 14, 2024, the target date by which the FDA intends to complete its review and take action on the NDA.

In April 2023, Madrigal announced that resmetirom received Breakthrough Therapy designation from the FDA for the treatment of patients with NASH with liver fibrosis. Also in April 2023, Madrigal announced that the outcomes portion of the Phase 3 MAESTRO-NASH biopsy trial completed enrollment.

In December 2022, Madrigal announced topline results from the pivotal Phase 3 MAESTRO-NASH biopsy study of resmetirom and the primary results were published in the New England Journal of Medicine in February 2024. Resmetirom achieved both primary endpoints with both daily oral doses, 80 mg and 100 mg, relative to placebo. In January 2022, Madrigal announced topline results from the Phase 3 MAESTRO-NAFLD-1 safety study of resmetirom. In August 2022, the company announced initiation of MAESTRO-NASH OUTCOMES, a Phase 3, double-blind, randomized, placebo-controlled study that will noninvasively measure progression to liver decompensation events in approximately 700 patients with compensated NASH cirrhosis. Resmetirom is a once-daily, oral, liver-directed THR-ß agonist designed to target key underlying causes of NASH. Resmetirom was discovered at Hoffmann-La Roche, or Roche, in Nutley, New Jersey, by utilizing a novel functional assay that, unlike a simple receptor binding assay, assessed the functional activity of compounds which interacted with thyroid hormone receptors.

Strategy

The key elements of the company’s strategy are to obtain regulatory approval of resmetirom in NASH; deliver on the U.S. launch of the first-to-market medicine for NASH; and expand its commitment to NASH.

The company intends to launch resmetirom as a specialty medication for patients with NASH with significant fibrosis (consistent with fibrosis stages 2 and 3) treated by liver specialist physicians. The company’s commercial strategy in the U.S. includes a focus on access to therapy. We will distribute resmetirom through a specialty pharmacy network and, to support patient access and affordability, it will provide patient support services including reimbursement programs and educational support to help appropriate patients initiate and remain adherent to resmetirom therapy.

Collaborations

VIA Pharmaceuticals, Inc., or VIA, entered into a research, development and commercialization agreement, or the Roche Agreement, with Roche, on December 18, 2008. The company subsequently assumed all of VIA’s rights in, to and under, and all of VIA’s obligations under, the Roche Agreement pursuant to an asset purchase agreement, dated September 14, 2011. Pursuant to the terms of the Roche Agreement, the company, as successor-in-interest to VIA, assumed control of all development and commercialization of resmetirom and will hold exclusive worldwide rights for all potential indications.

Commercial Organization

The company has established a commercial leadership team with expertise in launching pharmaceutical products. As of December 31, 2023, Madrigal had built out a field sales team and product launch capabilities in anticipation of potential accelerated approval in the U.S. for resmetirom.

Research and Development

The company’s research and development expenses were $272.4 million for the year ended December 31, 2023.

Intellectual Property

As of December 31, 2023, the company owned or co-owned seven United States and 44 foreign issued patents; nine United States and 70 foreign pending patent applications; and two international patent applications filed under the Patent Cooperation Treaty. Each of these patents and applications relates to resmetirom, including composition-of-matter, certain polymorph forms, methods of making resmetirom, its use in the treatment of key disease indications, or other THR beta analogs and uses thereof. The company’s patent portfolio covers the United States and certain other jurisdictions worldwide. The two international patent applications can be used as the basis for multiple additional patent applications worldwide. In addition, pursuant to the Roche Agreement, Roche granted the company an exclusive license to certain United States and foreign patents and patent applications owned by Roche and Roche know-how relating to resmetirom. The Roche Agreement imposes various diligence, milestone payment, royalty payment, insurance, indemnification, and other obligations on the company.

Issued patents directed to resmetirom have statutory expiration dates between 2026 and 2037, excluding any patent term extensions or equivalents thereof that might be available following the grant of marketing authorizations. The company has pending patent applications for resmetirom that if issued, would be expected to expire in the United States and in countries outside of the United States between 2033 and 2044, excluding any patent term adjustment that might be available following the grant of the patent. The company has a pending patent application for other THR beta analogs that, if issued, would be expected to expire in the United States and in countries outside of the United States in 2043, excluding any patent term adjustment that might be available following the grant of the patent.

Government Regulation

Any drug products manufactured or distributed by the company pursuant to FDA approvals are subject to continuing regulation by the FDA, including, among other things, record-keeping requirements, reporting of adverse experiences with the drug, providing the FDA with updated safety and efficacy information, drug sampling and distribution requirements, complying with certain electronic records and signature requirements, and complying with FDA promotion and advertising requirements.

When conducting clinical trials in the EU, the company must adhere to the provisions of the EU Clinical Trials Directive and the laws and regulations of the EU Member States implementing them.