Semaglutide’s MASH Approval: A New Era for GLP-1 Therapies in Liver Disease

The biotech sector is abuzz with news that Health Canada has accepted a supplemental new drug submission (sNDS) for semaglutide 2.4 mg, a once-weekly GLP-1 receptor agonist (GLP-1 RA), for the treatment of metabolic dysfunction-associated steatohepatitis (MASH). This marks a critical step toward addressing a condition with no approved therapies in Canada and a rapidly growing global patient population. If approved, semaglutide could carve out a new market segment for Novo Nordisk (NVO), building on its existing dominance in obesity and diabetes treatments.

The Science Behind Semaglutide’s MASH Potential

MASH, a progressive liver disease linked to obesity and insulin resistance, affects approximately 5.2% of Canadian adults—a number projected to rise to 6.5% by 2030. Untreated, it can progress to cirrhosis, liver cancer, or the need for transplantation. Semaglutide’s mechanism as a GLP-1 RA offers a dual advantage: it promotes weight loss and improves metabolic health, both of which are critical in managing MASH.

The Phase 3 ESSENCE trial, pivotal for this submission, demonstrated statistically significant improvements in key histological outcomes. At 72 weeks, 62.9% of semaglutide-treated patients achieved resolution of steatohepatitis (liver inflammation) without worsening fibrosis, compared to 34.3% on placebo (p < 0.001). Fibrosis improvement occurred in 36.8% of treated patients versus 22.4% on placebo. These results, alongside supportive data from non-invasive liver tests, position semaglutide as a first-in-class therapy for MASH.

Regulatory Momentum and Market Opportunity

Health Canada’s Priority Review designation, which fast-tracks assessment timelines, underscores the urgency of addressing this unmet medical need. The U.S. FDA also granted Priority Review for semaglutide’s MASH indication in April 2025, with a decision expected by late 2025. If approved in both markets, semaglutide could become the first therapy for MASH in Canada and the second in the U.S. (after resmetirom).

Novo Nordisk’s stock has risen steadily over the past two years, reflecting investor confidence in its GLP-1 pipeline. However, the MASH indication could provide a significant tailwind. The global MASH drug market is projected to exceed $5 billion by 2030, driven by rising obesity rates and aging populations. With semaglutide’s proven efficacy in histological improvements and its established safety profile in obesity trials, it is well-positioned to capture a substantial share of this market.

Risks and Challenges

While the data is compelling, several risks remain. First, pricing negotiations in Canada’s single-payer system could limit reimbursement rates. Second, competition from emerging therapies like resmetirom (already approved in the U.S.) may pressure market share. Third, long-term outcomes from the ESSENCE trial’s Part 2—which evaluates liver-related clinical events over 240 weeks—are pending, and any adverse findings could temper enthusiasm.

Additionally, semaglutide’s boxed warning for thyroid C-cell tumors (a risk shared with all GLP-1 RAs) may deter some prescribers, though this risk is considered rare.

Conclusion: A Transformative Moment for Liver Disease Treatment

Semaglutide’s MASH approval could redefine treatment paradigms for a disease that affects millions but has been historically overlooked. With a 62.9% histological improvement rate versus placebo, it offers a tangible solution to a condition that currently has no approved therapies in Canada.

The numbers are clear:
- 1 in 20 Canadian adults live with MASH, a number expected to grow.
- 32.7% of patients achieved dual improvements in steatohepatitis and fibrosis with semaglutide—nearly double the placebo rate.
- The $5 billion MASH market offers a compelling growth avenue for Novo Nordisk, which already commands over 80% of the global GLP-1 RA market.

While regulatory and commercial hurdles remain, the ESSENCE trial’s robust data and the priority reviews in both Canada and the U.S. suggest a high likelihood of approval. For investors, this represents a rare opportunity to capitalize on a novel indication for an established drug, with the potential to unlock significant value in a critically underserved therapeutic area.

In a world where obesity-related comorbidities are increasingly prevalent, semaglutide’s MASH approval could mark the dawn of a new era in liver disease management—and a profitable one for Novo Nordisk.