Of all the R&D-stage pharmaceuticals in Evaluate Pharma’s database, Novo Nordisk’s cagrisema carries the highest forecast sales, with the sellside expecting 2030 revenues of a staggering $21bn in diabetes and obesity combined. The readout of its pivotal obesity trial is due this quarter, and anything short of a slam-dunk could hurt Novo badly.
Key Takeaways
- The Phase III obesity trial of Novo Nordisk’s cagrisema will read out by the end of the year, and anything less than 25% weight loss could cause a sharp fall in Novo’s share price.
- Phase II data on Amgen’s obesity asset MariTide will also come in the same time frame, and if this does not hit 20%-25% weight loss, the consequences could be even more dramatic.
Another clinical-stage product is also about to yield some obesity data. Forecasts for Amgen’s MariTide are not as high as those for cagrisema, reflecting its earlier status, but the Phase II trial’s outcome will also be crucial to its developer’s fortunes. Here, Scrip previews these readouts and what they might mean for Novo and Amgen.
Target of 25%
Cagrisema is a combination of cagrilintide, a dual amylin and calcitonin receptor agonist, and semaglutide, the GLP-1 agonist already marketed as Ozempic for diabetes and Wegovy for obesity. Cagrilintide is an analog of amylin, a peptide released alongside insulin from beta cells in the pancreas, which has broadly the same effects as GLP-1, both slowing gastric emptying and inducing satiety, though it does not directly cause insulin secretion.
The combo skipped Phase II in obesity, though both its components have separately been trialed in the disease. Instead Novo began the Phase III REDEFINE 1 study in 2022.
Novo is riding high on the blockbuster sales of its incretins, principally the various forms of semaglutide. While this is of course a good thing, it exposes the Danish group to risk in that it has further to go down than up. Berenberg analysts highlighted this in a note dated 25 September, writing that “disappointing cagrisema Phase III data are likely to result in a more significant share price reaction for Novo Nordisk than a positive readout.”
And the benchmark for what counts as “a positive readout” is very high indeed. Investors expect weight loss of 25% over the 68-week duration of the trial. At this same time point, Wegovy managed weight loss of 15% in its pivotal obesity trial, and Lilly’s Zepbound (tirzepatide), the second best-selling obesity product, achieved 23% at the later point of 72 weeks (around a year and five months).
If cagrisema does hit this 25% goal, Novo’s shares could pop by up to 10%, the analysts wrote, and Lilly’s could drop by up to 5%. But what if it falls short?
If cagrisema is no better than Wegovy, Novo’s stock could fall by 10%-20%, is the salutary conclusion. And if it comes in actually worse than Wegovy, Novo could shed 20% or even 30% of its market cap. If cagrisema is matches Zepbound, meanwhile, any share price shift for Novo is hard to call, though Lilly’s will likely climb slightly.
The other concern is safety. Bernstein analysts point out that in cagrisema’s Phase II trial in diabetes, the frequency of gastrointestinal adverse events was almost doubled with the combination compared with each component alone, at 58% with the combo versus 32% with semaglutide and 33% with cagrilintide.
Quarterly
While forecasts for MariTide, Amgen’s obesity play, are lower than cagrisema’s, they are still substantial at $4.2bn in 2030, according to Evaluate Pharma’s consensus. That is high enough to qualify it as one of the top five bestselling obesity drugs in six years’ time.
MariTide – short for maridebart cafraglutide, and formerly known as AMG 133 – is a bispecific molecule that is, uniquely among therapies in clinical development for metabolic disorders, a GLP-1 receptor agonist but a GIP receptor antagonist. Several others, including Zepbound, are dual agonists. MariTide consists of two GLP-1 agonist peptides linked to an anti-GIP antibody backbone; Amgen believes MariTide might be the most advanced antibody-drug conjugate outside cancer.
The big upcoming readout for the drug will be that of a 600-patient Phase II trial in patients with overweight or obesity, with or without type 2 diabetes. Data on weight loss after a year’s treatment will come in the next few months, and again expectations are high.
Cantor Fitzgerald analysts are looking for 20%-25% weight loss, though they add that “anything around 20% should be viewed as good enough.” If MariTide hits this benchmark they believe Amgen’s share price could climb to $375 – an 18% rise from its closing price on 21 October. But, as with Novo’s readout, the downside is greater than the upside. Should the study disappoint, the company could lose 20% of its value, the analysts believe.
Investors will also want to see a tolerability profile similar to those of Wegovy and Zepbound, to wit patient discontinuation no higher than 20% and rates of nausea and vomiting below 40% and 15%, respectively.
MariTide’s big point of differentiation is its less frequent dosing compared with the weekly injections necessary for Wegovy and Zepbound (and cagrisema). The bispecific could be taken via autoinjector once a month or even less frequently, with William Blair analysts mooting the possibility of quarterly maintenance dosing. This could help keep a lid on side-effects, but also sidestep issues around manufacturing enough of the API, something with which Novo Nordisk and Lilly are still grappling.
Amgen is confident of decent data in Phase II, having shuttered its other obesity candidate, AMG 786, in favor of MariTide, and is already planning a Phase III program. But the risk is real, for both these products. Investors will have little mercy if they do not hit their goals.
