The first company to bring a treatment for metabolic dysfunction-associated steatohepatitis (MASH) to market, Madrigal Pharmaceuticals is redefining how the world tackles fatty liver disease. From its new European base in Zug, the firm is building an entirely new therapeutic category while spearheading one of the most ambitious global launches in recent memory.
Diabetes and obesity rates are skyrocketing, and people are living longer than ever with these conditions. This has knock-on effects on a whole host of bodily functions, not least the liver – the organ which filters toxins, processes nutrients, regulates energy, and produces essential substances that keep the body functioning and healthy.
Incidence of MASH – a serious and widespread form of fatty liver disease – is soaring in tandem with the diabetes and obesity epidemic. Around five to seven percent of adults – or between 400 and 500 million people worldwide – are thought to have MASH and an estimated 15 to 20 million in major markets like the US, Europe, Japan, and China have advanced fibrosis and are therefore eligible for drug therapy.
However, until 2024, there were no dedicated therapeutic options for MASH patients. A notoriously tricky target, MASH saw more than 20 companies fail Phase 3 trials between 2015 and 2022 thanks to the disease’s complex biology (MASH is a mix of fat metabolism, inflammation and tissue scarring rather than a single factor); diagnosis challenges (making clinical trial recruitment a challenge); and regulatory uncertainty (until recently, regulators had no agreed surrogate endpoints for approval, meaning that companies were not able to show success without long, expensive outcome studies).
A breakthrough finally came last year when the US FDA approved a new compound for MASH from Madrigal Pharmaceuticals. A single asset player that was able to pour all its resources into MASH while its competitors fell by the wayside, Madrigal worked with the FDA to create new accelerated approval endpoints for the entire field. Its drug treats the underlying cause of MASH – excess fat and poor metabolism in the liver – in high-risk late-stage patients rather than just the damage it causes. Earlier this year, the drug also received conditional approval from the European Medicines Agency.
This means that Madrigal’s team – including its EVP for international markets and first full-time employee outside of the US Neil Archer – is faced with the daunting challenge of bringing a product to a market that did not previously exist. “We are not merely launching a new medicine but creating an entire disease category, encompassing public awareness, diagnostic pathways, and treatment protocols,” explains Archer.
Based out of Zug, Archer and his team have set about the head-spinning task of international product launches methodically. Going country by country across Europe – where Archer estimates more than 350,000 patients may be eligible – he emphasises collaboration with four key stakeholder groups: patient organisations, the clinical community, payers, and government.
“The stakeholder response has been remarkably positive and unanimous,” exclaims Archer. “Every stakeholder group demonstrates strong support for Madrigal’s mission. This partly reflects recognition of our tenacity and persistence in a therapeutic area where significantly larger, better-resourced organisations had previously failed.”
Madrigal plans to launch first in Germany, typically Europe’s fastest launch market, where commercialisation is allowed prior to (rather than after) the conclusion of pricing and reimbursement negotiations. Archer has also established small leadership teams ahead of launches in the UK, France, Italy and Spain, while considering distribution partnerships in smaller markets like Central and Eastern Europe, Israel, and the Middle East.
All this necessitates a team able to hit the ground running, a key factor in the decision to base international operations out of Switzerland. “We require experienced professionals capable of immediate impact,” asserts Archer. “Traditional European launch preparation typically begins 24 months before approval; we had nine months, realistically six, requiring individuals who could execute immediately without extensive onboarding.”
Madrigal seems eager to embrace the responsibility of being a first mover, with Archer unperturbed by the prospect of new market entrants in the MASH space. “By 2028, we will have established definitive leadership in the treatment of MASH,” he proclaims. “I hope we will no longer be alone in this therapeutic space, with our success enabling other treatment options to reach the market, ultimately benefiting patients with this condition. However, our asset and Madrigal should be recognised as the foundational platform upon which all subsequent MASH therapeutic developments have been built.”
“This represents arguably the most exciting opportunity currently available in our industry, a truly unique prospect with substantial future potential,” concludes Archer. “The MASH therapeutic category is just beginning its development, and there is much more innovation to come.”
