MASH (metabolic dysfunction-associated steatohepatitis) is an inflammatory form of fatty liver disease, strongly linked to obesity, diabetes, and metabolic syndrome. The most critical stage is F4 MASH, or cirrhosis — the end stage of liver fibrosis. For these patients there are currently no approved drugs, only lifestyle interventions, management of complications, and, in severe cases, liver transplantation.
This is where biotech companies see massive opportunity: any therapy that slows or reverses disease progression could be worth billions.
Roche Buys 89bio
In September 2025, Roche announced its acquisition of 89bio:
- Price: $14.50 per share in cash
- Plus: up to $6 in Contingent Value Rights (CVRs), linked to three ambitious milestones
- Pipeline: Pegozafermin, an FGF21 analogue currently in Phase 3 for MASH (F2–F4) and severe hypertriglyceridemia (SHTG).
The Three CVR Milestones
- First commercial sale of Pegozafermin in F4 MASH by March 31, 2030
- Annual global sales ≥ $3.0B in a single year by December 31, 2033
- Annual global sales ≥ $4.0B in a single year by December 31, 2035
Regulatory Challenge: Histological Surrogates
For F2–F3, FDA accepts surrogates such as:
- ≥1-stage fibrosis improvement without worsening MASH
- or NASH resolution without worsening fibrosis
This was the basis for the Accelerated Approval of Resmetirom (Rezdiffra™, Madrigal) in 2024.
But for F4, the situation is different:
- The liver is already heavily scarred; histological “improvement” is harder to prove.
- FDA guidance emphasizes clinical outcomes (decompensation, transplant, survival).
- Histological surrogates are not validated in cirrhosis.
In short: accelerated approval in F4 is possible but highly uncertain.
Madrigal as the Market Leader
Madrigal Pharmaceuticals is currently the frontrunner:
- Resmetirom was FDA-approved in 2024 for F2–F3 MASH.
- For F4, the MAESTRO-NASH OUTCOMES trial (~700 patients) is underway, measuring hard clinical endpoints.
- This gives Madrigal a stronger regulatory footing, even if timelines are longer.
By contrast, Roche/89bio are aiming to leverage histological surrogates for F4 accelerated approval. FDA/EMA have signaled “alignment,” but that is not a guarantee.
Why Roche’s Milestones Look Unrealistic
-
F4 launch by 2030:
- Topline data only expected in 2028 → very tight.
- Accelerated approval in F4 on histology alone is highly uncertain.
-
≥ $3B sales by 2033:
- Analyst peak sales forecasts for Pegozafermin are closer to ~$2B.
- Intense competition from Madrigal, Akero, Novo Nordisk, GLP-1 combos.
-
≥ $4B sales by 2035:
- Would require best-in-class status and dominant share.
- Given competition and regulatory risk, this looks extremely unlikely.
Conclusion
Roche’s acquisition of 89bio adds a promising FGF21 candidate to its metabolic pipeline. Pegozafermin has strong Phase 2 data and is progressing in Phase 3.
But the CVR milestones are extraordinarily ambitious:
- Near-term: Launch in F2–F3 or SHTG is realistic.
- F4 & multi-billion sales: Regulatory hurdles, timelines, and competition make these goals far less likely.
The CVRs read more like an optimistic “best case” lottery ticket than a realistic forecast.
Although the merger is expected to close in Q4 2025, I will listen closely to the November 6, 2025 earnings call of 89bio (ETNB). If they confirm the deal is imminent and the stock still trades below $15, buying some shares could be a short-term lottery ticket trade: limited downside, but up to $6 upside if the CVR ever pays out.