Eli Lilly’s retatrutide could reduce the burden of unstable angina or myocardial infarction by up to 570k cases in the US by 2030
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Weight loss drugs pose potential to reduce prevalence of unstable angina and myocardial infarction.
Airfinity data indicate that in 2024 there are 8.6 million adults living with obesity and unstable angina or history of myocardial infarction in the US, and by 2030, this will grow to 11.1 million adults. Increasing obesity prevalence is the driver of this, with the excess number of people living with unstable angina or a history of myocardial infarction and obesity is projected to increase by ≈32% over the next 6 years. This is smaller than other obesity comorbidities that Airfinity has investigated, for example the excess burden of hypertension and type 2 diabetes are ≈19-fold and ≈9-fold greater. Weight loss interventions can offset this risk, by reducing obesity prevalence and therefore risk of cardiovascular disease/events.
Airfinity forecasts that with high coverage among patients with Class II and III obesity, Novo Nordisk 's Wegovy could reduce the burden of unstable angina and myocardial infarction in 2030 by 290,000 cases, while Eli Lilly and Company 's Zepbound could reduce burden by 420,000 cases and its Retatrutide by 570,000 cases.
Please reach out to obesity@airfinity.com for more information on these market forecasts and customised scenarios.
Wegovy improves quality of life in patients with HFpEF, obesity and type 2 diabetes
The results of the STEP HFpEF DM and combined analysis with the STEP HFpEF study were presented at ACC 24 and published in The Lancet and New England Journal of Medicine. STEP HFpEF utilised the Kansas City Cardiomyopathy Questionnaire - Clinical Summary Score (KCCQ-CSS) quality of life metric as the primary endpoint, similar to STEP HFpEF, and examined the impact of Wegovy on this in patients with type 2 diabetes, HFpEF (heart failure with preserved ejection fraction) and obesity. Across the 52-week study, patients treated with Wegovy gained 13.7 KCCQ-CSS points, 7.3 points more than placebo. This was accompanied by 9.8% reduction in body weight. Pooled analysis from both studies indicated a mean increase of 15.0 KCCQ-CSS points and 11.4% reduction in body weight. Current guidance from the Cardiovascular Outcomes Research Consortium indicates a score change of 5, 10, and 22 points denote small, moderate and large improvements in quality of life. With a placebo-controlled change of 7.3 points, this would categorise the effect of Wegovy as small to moderate.
In 2020, the FDA made the amendment to the KCCQ to be a primary clinical trial endpoint, signifying the value of quality of life metrics to regulators. However, they should be interpreted with caution. For example, the RELIEVE-HF trial, also presented at ACC, demonstrated that HFpEF patients in whom an atrial shunt system was surgically implanted, an atrial shunt system had significantly more cardiovascular events (hospitalisation for/worsening of heart failure and all-cause death) than matched controls who underwent sham surgery. Both groups, however, reported equal increases in the KCCQ-CSS scoring, which were numerically comparable to the increase in KCCQ-CSS score demonstrated by the placebo group in STEP HFpEF DM. This indicates that there can be scenarios where patients think they are improving, but physiologically they are worsening.
On the whole, the data is positive for Novo Nordisk, who indicated in their Capital Market Days meeting in March that they would be pursuing a HFpEF label expansion. Given these trials did not demonstrate hard endpoints, it may be difficult for Wegovy to get first-line treatment choice for HFpEF - which is exclusively limited to SGLT2i class as it stands. In an interview with Radcliffe Cardiology Lead author and presenter, Dr Kosiborod did concede that they will be pursuing further trials to explore these hard endpoints.
Chinese and Russian authorities approve the development of semaglutide biosimilars
Russian authorities have given permission for Geopharm approval for the development of a Wegovy biosimilar. Geopharm plans to launch the drug to market in 2025. A similar scenario is playing out in China too, with Jiuyuan Engineering of Hangzhou seeking approval for an Ozempic biosimilar, named Jiyoutai. Novo Nordisk’s China patent for Ozempic is set to expire in 2026. This launch of biosimilars presents significant potential for generics to eat into the booming GLP-1RA obesity market, with potential sales and revenue implications for Novo Nordisk. This comes at a time where Wegovy is nearing three years on the market, with Novo Nordisk EVP, Camilla Sylvest stating “We haven't fully seen how much demand there really is”.
The EMA is meeting to review links between GLP-1RA and suicidal ideation reports
The European Medicines Agency will hold its meeting into the ongoing investigation related to GLP-1R agonist use and potential links to suicidal thoughts. In January, the FDA concluded its preliminary investigation stating that from various sources of data that “the information in these reports did not demonstrate a clear relationship with the use of GLP-1 RAs”. Last month Guirguis et al., published a study in European Neuropsychopharmacology, where they examined 59,300 serious cases of adverse drug reactions reported in the Food and Drug Administration Adverse Events Reporting System (FAERS) related to GLP-1RAs and weight loss drugs between 2005-2023. These data showed no clear relationship between GLP-1RA use and suicidal ideation. Similarly in January, another group concluded from a real-world cohort of semaglutide users, that their risk of suicidal ideation was lower than those taking non-GLP-1RA weight loss drugs. These data indicate that the EMA is likely to come to a similar positive conclusion as the FDA.
News Highlights
Bloomberg - 8 April 2024
Reuters - 8 April 2024
PR Newswire - 10 April 2024
Medwatch - 10 April 2024
Endpoints News - 11 April 2024
Reuters - 8 April 2024
MDedge - 9 April 2024
Jerusalem Post - 9 April 2024
Financial Times - 10 April 2024
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