TLDR
- Petrelintide achieved 10.7% weight reduction at 42 weeks in Zealand Pharma’s Phase 2 study — falling short of the 12–15% analyst forecast
- Wall Street analysts from JPMorgan, Jefferies, UBS, and Barclays expressed disappointment with the readout
- Cantor Fitzgerald slashed its rating to Neutral from Overweight citing limited competitive advantages
- Competing therapies from Eli Lilly (eloralintide) and Novo Nordisk (cagrilintide) appear more promising
- Absence of clear dose-response relationship between highest dose cohorts raises doubts about Phase 3 improvement potential
Shares of Zealand Pharma (ZEAL) plummeted over 32% on Friday following the release of Phase 2 clinical data for petrelintide, its experimental obesity treatment, which underperformed Wall Street’s benchmarks.
The ZUPREME-1 study, conducted in collaboration with Roche, evaluated petrelintide in overweight and obese participants who did not have type 2 diabetes. The top dose cohort achieved an average weight reduction of 10.7% at the 42-week mark using an efficacy estimand analysis.
While the study successfully achieved its primary efficacy measure — demonstrating statistically significant weight reductions at 28 weeks across all treatment arms compared to placebo — the topline figure disappointed the investment community.
Street consensus had positioned competitive viability around the 12% to 15% weight loss range. The 10.7% outcome fell meaningfully below that threshold.
JPMorgan analyst Sophia Graeff Buhl Nielsen characterized the outcome as “falls slightly short of expectations,” though she noted the data “leaves scope for an attractive mid-teens weight loss profile to be achieved in Phase 3,” particularly if enrollment skews toward female participants who demonstrated more robust responses.
Jefferies identified the result as likely to trigger negative sentiment, coming in below both its internal projection of 13% to 15% and buy-side expectations exceeding 15%. Analyst Lucy Codrington described petrelintide as having “Wegovy-like efficacy, but with placebo-like tolerability,” calling it “viable” though probably “2nd-best to LLY’s elora for now.”
On the safety front, the drug showed promise. The highest-dose cohort reported zero vomiting events and minimal gastrointestinal adverse effects — a tolerability profile Codrington described as “placebo-like.” While this represents a clear advantage, it wasn’t sufficient to offset efficacy concerns.
Cantor Fitzgerald Downgrades to Neutral
Cantor Fitzgerald downgraded Zealand Pharma from Overweight to Neutral, citing insufficient differentiation versus competitors. The firm noted petrelintide’s placebo-adjusted weight reduction of approximately 9% at 42 weeks matches Novo Nordisk’s cagrilintide — and trails significantly behind Eli Lilly’s eloralintide.
Cantor highlighted the absence of dose-response separation as problematic, suggesting limited evidence that weight loss outcomes will meaningfully improve in pivotal trials. The firm now projects petrelintide will deliver weight loss in the low-teen percentage range, comparable to cagrilintide.
Given that Eli Lilly has already advanced eloralintide into Phase 3 and Novo Nordisk has similarly progressed cagrilintide monotherapy, Cantor believes petrelintide risks becoming a third-to-market entrant with minimal differentiation. That presents significant commercial headwinds.
What’s Left to Watch
UBS observed the trial results landed “clearly at the lower end of expectations” and questioned petrelintide’s viability as a standalone treatment. Nevertheless, the bank identified a combination strategy — pairing petrelintide with low-dose CT-388 from Roche — as a “still viable option,” leveraging the compound’s favorable tolerability characteristics.
The study also revealed minimal separation between top dose groups, with weight loss spanning 10.2% to 10.7%. JPMorgan suggested this pattern may indicate limited incremental benefit from dose escalation.
Comprehensive trial findings are scheduled for presentation at a scientific conference in 2026.
Shares were trading at $38.22 at last check, representing a roughly 51% decline from the 52-week high of $112.63.
