CagriSema
cagrilintide + semaglutide
With its addition of cagrilintide, a long-acting amylin analog, to semaglutide, CagriSema promises to offer better efficacy than semaglutide (OZEMPIC/WEGOVY®) and tirzepatide (MOUNJARO/ZEPBOUND®) for both obesity and T2DM. This next-generation GLP-1 agent combines the known advantages of GLP-1s, such as enhanced post-prandial insulin secretion by pancreatic beta cells and slowed gastric emptying for reduced appetite, with the activity of amylin, including slowed intestinal glucose absorption and release of post-prandial hepatic glucose. If approved, CagriSema will be the first FDC amylin and GLP-1 RA to launch in the obesity and T2DM markets.
About CagriSema
- Novo Nordisk
- Fixed dose combination (FDC) of a GLP-1 RA (semaglutide) + long-acting amylin analog (cagrilintide)
- Once-weekly SC administration to treat obesity and T2DM
- ~3.32m drug-treated prevalent cases of overweight and obesity in the G7 markets in 2024
- ~45.4m drug-treated prevalent cases of T2DM in the G7 markets in 2024
Why is it a drug to watch?
Obesity and T2DM are widespread diseases that are responsible for considerable levels of morbidity and mortality globally, primarily in the form of cardiovascular disease (CVD). Therapies based on incretin hormones, spearheaded by GLP-1 RAs, are becoming the preferred choice of treatment for obesity and T2DM. Moreover, there is now clinical evidence suggesting that these agents also have the potential to provide cardiovascular and renal benefits.
CagriSema, a once-weekly SC FDC injection, resulted in a significant weight reduction in a phase 2 clinical trial with individuals with T2DM and BMI ≥27.0 kg/m2:
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CagriSema vs cagrilintide vs semaglutide for 32 weeks
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Weight reduction: 15.6% vs 8.1% vs 5.1%
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CagriSema was well-tolerated.
Phase 3 trials are ongoing for obesity, in which the dose for CagriSema (2.4 mg) is the same as the dose of WEGOVY for obesity and higher than the approved doses of OZEMPIC for T2DM (0.5 mg, 1 mg and 2 mg):
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REDEFINE 1: adults ≥18 years old with BMI ≥27.0 kg/m2 and at least one weight-related comorbidity (e.g., hypertension, dyslipidemia, obstructive sleep apnea or CVD)
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Once-weekly SC CagriSema vs SC semaglutide vs SC cagrilintide vs placebo for 68 weeks)
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Primary endpoints:
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Mean placebo-adjusted change in body weight from baseline
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Percentage of participants achieving ≥5% body weight reduction
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Weight reduction: 22.7% vs 16.1% vs 11.8% vs 2.3%
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Proportion with weight loss >25%: 40.4% vs 16.2% vs 6.0% vs 0.9%
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Proportion at the highest dose: 57.3% vs 70.2% vs 82.5%
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CagriSema was well-tolerated
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REDEFINE 2: adults ≥18 years old with BMI ≥27.0 kg/m2 and T2DM
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Once-weekly SC CagriSema vs SC semaglutide in combination with placebo for 68 weeks
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Primary endpoints:
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Mean placebo-adjusted change in body weight from baseline
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Percentage of participants achieving ≥5% body weight reduction
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Expected completion: January 2025
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REDEFINE 3: adults ≥18 years old with BMI ≥27.0 kg/m2 and established CVD, with or without T2DM
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Once-weekly SC CagriSema vs placebo for 163 weeks
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Primary endpoints:
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Time to first occurrence of MACE-3 (CVD death, nonfatal myocardial infarction, nonfatal stroke)
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Expected completion: May 2027
NDA submission is expected to be supported by the results from REDEFINE 1 and REDEFINE 2.
The following trials are also ongoing for T2DM, with varying doses of CagriSema within and between trials:
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REIMAGINE 1: adults ≥18 years old with T2DM
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Once-weekly SC CagriSema for a 16-week dose escalation period and 24-week maintenance period vs placebo
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Primary endpoints:
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Change in HbA1c
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Expected completion: December 2025
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REIMAGINE 2: adults ≥18 years old with T2DM inadequately controlled with metformin with or without an SGLT2 inhibitor
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Once-weekly SC CagriSema vs SC semaglutide vs SC cagrilintide vs placebo for 68 weeks
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Primary endpoints:
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Change in HbA1c
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Relative change in body weight
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Expected completion: May 2026
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REIMAGINE 3: adults ≥18 years old with T2DM on once-daily insulin with or without metformin
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Once-weekly SC CagriSema for an 8-week dose escalation period and up to a 32-week maintenance period vs placebo for 40 weeks
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Primary endpoints:
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Change in HbA1c
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Expected completion: November 2025
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REIMAGINE 5: adults ≥18 years old with T2DM inadequately controlled with metformin, an SGLT2 inhibitor or both
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Once-weekly SC CagriSema for an 8-week dose escalation period and 52-week maintenance period vs once-weekly SC tirzepatide for a 4-week dose escalation period and 56-week maintenance period
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Primary endpoints:
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Change in HbA1c
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Relative change in body weight
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Expected completion: August 2026
Review and approval status
Actual and expected launch:
- 2026: United States (obesity)
- 2027: European Union (obesity), Japan (obesity), Mainland China (obesity and T2DM)
- 2028: European Union (T2DM), Japan (T2DM), United Kingdom (T2DM), United States (T2DM)
Patents estimated to expire beginning in 2026
Drug Timeline & Success Rates
Source: Cortellis Competitive Intelligence, Drug Timeline & Success Rates Prediction current as of October 31, 2024
How will CagriSema impact the market for obesity and T2DM?
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The obesity therapy market is poised for significant expansion, with major-market sales of branded, generic and off-label obesity drug treatments expected to grow from $2.8bn in 2022 to more than $22bn in 2032, a CAGR of 23%.
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GLP-1 RAs accounted for approximately 96% and 91% of total obesity market sales in the United States and EU5, respectively, in 2023, placing them as sales leaders.
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The T2DM market is forecast to expand, with major-market sales growing from $102bn in 2022 to more than $127bn in 2032. This robust growth will be driven by the launch and uptake of emerging therapies, the growing use of branded therapies (such as GLP-1 RA products) and an increasing drug-treated population. However, the entry of non-branded versions of many key T2DM brands is expected to exert downward pressure on market sales.
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Sales of the GLP-1 RA products are expected to continue to increase significantly through 2032. These drug classes are forecast to continue being the most lucrative throughout the forecast period, with anticipated combined sales of more than $74bn in 2032 in the major markets.
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Although WEGOVY has led GLP-1 RAs in sales, ZEPBOUND and CagriSema, with potentially better efficacy at competitive pricing, are expected to erode WEGOVY’s patient share. The two will also compete with each other, constraining each other’s sales.
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A number of factors will continue to drive market growth, including premium prices of highly efficacious drugs, increasing prevalence and treatment rates of obesity and T2DM, easier-to-use drugs and easing of access and reimbursement constraints based on improved disease outcomes beyond obesity and T2DM.
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The therapeutic pipeline for obesity and T2DM is becoming extremely competitive, and new GLP-1 RAs as monotherapy and in combination with other agents (e.g., insulin icodec [IcoSema]) being developed by market leaders are in the early-stage and late-stage pipeline. This promises to make this area even more crowded and competitive in the future.
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Dual and triple RAs promise superior efficacy, similar safety and tolerability profiles and prices equal to or less than GLP-1 RAs and GLP-1/GIP RAs already on the market.
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The ability to provide glucose management, CVD, renal and weight loss benefits has helped drive GLP-1 RA uptake, will help differentiate several of the novel drugs such as CagriSema launching in the next few years and will assist with reimbursement.
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CagriSema is expected to benefit from its semaglutide backbone, which is well-established for obesity and T2DM.
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For T2DM, emerging therapies from existing drug classes might have difficulty distinguishing themselves because of the available well-established GLP-1 RAs, according to KOLs interviewed by Clarivate. GLP-1 RA and GLP-1/GIP RA use has been displacing the use of other antidiabetic drug classes such as meglitinides and thiazolidinediones across the major markets.
What gaps in treatment does CagriSema fill?
Changes to lifestyle and behavior have insufficient long-term efficacy in most individuals with obesity and/or T2DM; metabolic surgery, although effective, is not practically deliverable on the scale that is required to address the public health concern represented by these diseases. The limited efficacy of current therapies and gastrointestinal side effects associated with GLP-1 RA products often lead to treatment discontinuation, weight regain and poor glycemic control. Further concerns for T2DM include the occurrence of microvascular complications, including retinopathy, neuropathy and nephropathy, which are not addressed by the long-standing mainstays of treatment. Despite their promise to address obesity and T2DM, GLP-1 and GLP-1/GIP RAs remain expensive in markets such as the United States and have limited coverage by payers except in the presence of CVD risks. With the launch of CagriSema and other dual and triple GLP-1 RAs that could be more effective for obesity and T2DM, barriers to improved coverage could be improved, making these drugs available to a larger population.
What hurdles might it need to overcome to reach blockbuster status?
The only amylin analog approved to date is SYMLIN® (pramlintide acetate; AstraZeneca), which is only available in the United States for T2DM. Safety concerns, such as the risk of severe hypoglycemia has prevented approval in the E.U. and Japan. The phase 3 program for CagriSema will need to alleviate any safety concerns associated with cagrilintide, both for approval and to foster positive physician perceptions. Even with robust safety data, physicians and patients alike might choose well-established and better known GLP-1 RAs and GLP-1/GIP RAs over CagriSema; comparable efficacy regarding weight loss and HbA1c management needs to be established in the phase 3 programs for obesity and T2DM. Furthermore, despite its promising efficacy profile, sales of CagriSema might be limited due to the ongoing challenging reimbursement environment, high out-of-pocket costs and limited physician familiarity with amylin analogs.
