Creating a Market from Scratch

The regulatory approval of Rezdiffra (resmetirom) for the treatment of noncirrhotic metabolic dysfunction-associated steatohepatitis (MASH) with moderate to advanced liver fibrosis (stages F2–F3) is a historic milestone for speciality pharma. As the first-ever approved therapy for MASH (formerly NASH), Rezdiffra's launch by Madrigal Pharmaceuticals has transitioned the disease from a space defined by lifestyle advice into a massive, multi-billion-dollar therapeutic market.

However, launching a first-in-class drug in a newly defined therapeutic area introduces unique commercial challenges. Without established clinical guidelines, standardized referral pathways, or dedicated reimbursement models, commercial success depends on a company’s ability to build a market from scratch. The blockbuster trajectory of Rezdiffra in 2025 and 2026 serves as a case study in how to navigate diagnostic bottlenecks and secure payer coverage in a new disease category.

Overcoming the Diagnostic Bottleneck with Non-Invasive Tests

Historically, confirming a diagnosis of MASH and staging liver fibrosis required a liver biopsy—an invasive, painful, and expensive surgical procedure that carries inherent patient risks. For a mass-market metabolic disease like MASH, relying on biopsies is a commercial impossibility.

To scale the adoption of Rezdiffra, commercial leadership had to pivot the diagnostic landscape toward Non-Invasive Tests (NITs):

• Standardising Screening Protocols: Commercial teams have collaborated with professional medical societies to integrate simple, blood-based screening tools—such as the FIB-4 index—directly into primary care workflows to identify at-risk patients early.

• Specialist Staging: To stage moderate-to-advanced fibrosis (F2–F3) without a biopsy, companies have driven the adoption of advanced NITs, including FibroScan (VCTE), Magnetic Resonance Elastography (MRE), and the Enhanced Liver Fibrosis (ELF) score.

• Monitoring Treatment Response: NITs are increasingly utilized as longitudinal monitoring tools, tracking liver stiffness and enzyme reductions at 3, 6, and 12-month intervals to justify ongoing therapy.

Navigating Payer Prior-Authorisation Cadences

As a high-value specialty medication, Rezdiffra is subject to rigorous prior-authorisation (PA) processes by health insurers and public payers. Initially, payers sought to restrict access by demanding biopsy confirmation of fibrosis.

Commercial market access teams resolved this bottleneck by:

• Securing NIT-Based Prior Authorisation: Negotiating agreements with major insurance providers to accept FibroScan or MRE data as sufficient evidence of F2–F3 fibrosis, bypassing biopsy requirements.

• Establishing Referral Gateways: Building digital tools to assist primary care physicians and endocrinologists (who manage the diabetic and metabolic patient populations most at risk for MASH) in screening and referring patients seamlessly to hepatologists and gastroenterologists.

• Demonstrating Long-Term Economic Value: Compiling health outcomes data showing that early intervention with Rezdiffra halts progression to cirrhosis, liver failure, and transplantation, offering payers significant long-term cost savings.

Sourcing Leaders for Market-Creation Launches

Succeeding in a new disease category requires a Chief Commercial Officer (CCO) or VP of Marketing with specific experience in market-creation launches. Executives accustomed to competing for market share in crowded, established indications often struggle with the educational and infrastructure-building requirements of a first-in-class launch.

RSA prioritises several core competencies when sourcing commercial leadership for newly approved therapeutic categories:

• First-in-Class Launch Track Record: A proven history of launching therapies in previously untreated or poorly defined disease areas, demonstrating the ability to build market awareness and shape clinical guidelines.

• Diagnostic Integration Strategy: Experience partnering with medical device and diagnostic companies to standardise testing protocols and secure reimbursement for companion screening tools.

• Payer Partnership and PA Navigation: The ability to negotiate complex prior-authorisation criteria with major health insurers, using real-world evidence to defend pricing and expand coverage.

By securing commercial leaders who can combine physician education, non-invasive diagnostic integration, and payer negotiation, speciality pharma companies can transform scientific breakthroughs into blockbuster commercial successes, establishing new standards of care for patients worldwide.