Roche and Zealand Pharma’s co-developed amylin analogue, petrelintide, has met its primary endpoint in a Phase II trial, but the data has garnered mixed analyst reaction.
During the Phase II ZUPREME-1 trial (NCT06662539), patients who received a once-weekly, subcutaneous dose of pertrelintide achieved a mean weight loss of 10.7% from baseline at 42 weeks – meeting the trial’s primary endpoint. This compares with the 1.7% mean weight loss observed in the placebo group.
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In a research note, William Blair analyst Andy Hsieh noted that the magnitude of weight loss observed in the ZUPREME study will likely diminish the real-world use-case for petrelintide due to the “hypercompetitive nature” of the obesity market.
While some analysts fear that petrelintide’s weight loss efficacy may come as a blow to its future market potential, Roche noted that the drug demonstrated “placebo-like tolerability”, with 98% of trial participants receiving petrelintide reaching the maintenance dose. The proportion of participants who vomited post-treatment was also lower in the treatment arms than in the placebo arm, with no vomiting observed in the maximally effective treatment arm. Discontinuations due to treatment-emergent adverse events (TEAEs) were 4.8% and 4.9%, respectively, in the treatment and placebo arms.
According to GlobalData managing analyst, Sara Reci, the ZUPREME study results “credibly endorse a very well-tolerated amylin backbone that can underpin future combination regimens”, naming petrelintide-CT-338 as an example.
However, Reci caveats that petrelintide is unlikely to become a near-term monotherapy leader, and its success as part of a combination hinges on if the drug can “approach or exceed GLP-1/GIP class efficacy, while improving gastrointestinal tolerability and patient experience”.
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By GlobalDataIt appears that many investors cannot see past the efficacy data, however, as Zealand Pharma’s stock value tumbled more than 36.4% on the Copenhagen exchange, reaching a value of DKr 234.90 ($36.44) at market close on 6 March from the DKr 369.20 rate seen at close on 5 March. Roche’s stock also fell 2.9% on the Swiss market from SFr 351.50 ($451.49) to SFr 341.30 during the same timeframes.
Roche originally secured the co-development and commercialisation rights to petrelintide and GLP-1/GIP agonist, CT-388, through a $5.3bn deal forged in March 2025.
Obesity market remains highly competitive
Amid the rapid sales growth of both injectable and oral obesity medications, pharma companies are increasingly seeking a slice of this market, which GlobalData forecasts will reach a value of $173.5bn across the seven major markets (7MM: France, Germany, Italy, Japan, Spain, the UK and the US) in 2031.
This includes big pharma players like AstraZeneca, Roche and Pfizer, with each company striking a multi-billion dollar deal in the disease area during recent times.
To compete with dominant forces Novo and Lilly, companies are looking to differentiate their offerings by exploring monthly, quarterly and oral dosing options, as well as combinations and drugs with better tolerability profiles.
Novo and Lilly are also looking to affirm their dominance in this sector with their respective ranges of next-generation injectable candidates – including the former’s GLP-1RA-amylin analogue combination, CagriSema and the latter’s triple GLP-1/GIP/glucagon agonist, retatrutide.
According to Edit Kovalcsik, senior director of R&A at GlobalData, amylin analogues “may possibly have better muscle preserving properties versus GLP-1RAs”, which could potentially address concerns held by scientists on the latter drug class’s potential to reduce a patient’s skeletal muscle mass during treatment.
