Eli Lily's Zepbound reduces symptoms of obstructive sleep apnea, while retatrutide could improving symptoms the most
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Welcome to this week's update from Airfinity on the latest developments across the obesity treatment landscape. Sign up for the full newsletter here .
SURMOUNT-OSA top line: Zepbound reduces symptoms of obstructive sleep apnea over one year
SURMOUNT-OSA examined the capacity of 礼来 's Zepbound to improve the apnea-hypopnea index (AHI) - a clinically quantifiable symptom of obstructive sleep apnea (OSA) - in patients with obesity and OSA. The study was split in two groups, those not using overnight breathing support, and those routinely using a continuous positive airways pressure (PAP) device. Over 52-weeks of treatment with once-weekly Zepbound (10-15 mg), the non-PAP group demonstrated a 55.0% reduction in AHI and the PAP group showed a numerically greater 62.8% reduction in AHI - positively correlating to the respective changes in body weight in each group. These data indicate that patients administered Zepbound experienced fewer episodes of breathing cessation or slowing vs baseline and placebo.
Interestingly, weight loss in SURMOUNT-OSA (-18.1% and -20.1%) was comparable to that seen in the SURMOUNT-1 trial (-20.9%), which examined weight loss efficacy of Zepbound in patients with overweight/obesity without type 2 diabetes. Patients with type 2 diabetes do not lose as much weight as those without diabetes with anti-obesity medications. For example, in SURMOUNT-2, patients with obesity and type 2 diabetes lost 14.7% of their weight. These data from SURMOUNT-OSA are interesting as this reduction in comorbidity-related weight loss efficacy does not seem to apply to OSA.
The below visual summarises the key primary endpoints from SURMOUNT-OSA (left), and Airfinity’s projections for two other anti-obesity medications (right). Zepbound reduces the average person’s OSA severity from severe to moderate.
Airfinity project that the greater weight loss efficacy of Lilly’s retatrutide (also currently being trialled for OSA efficacy in TRIUMPH-1), could reduce the severity even further, down to a clinically “mild” level - where patients would potentially not need breathing support, and thus? have a knock-on impact on the PAP device market.
Reports of increased fertility associated with anti-obesity drug usage: delving deeper
Recent weeks have seen numerous media reports of unexpected pregnancies in patients taking incretin mimetic drugs, such as Ozempic, Wegovy, Mounjaro, and Zepbound. Thus coining the widespread use of the term “Ozempic babies''. There is little scientific data to explain the exact mechanism linking use of these drugs to increased pregnancy likelihood. William Dietz, chair of the STOP Obesity Alliance, purported that GLP-1R agonists might affect the way birth control medications are metabolised. Data also indicate that elevated BMI is associated with infertility, whilst weight reduction can increase fertility. Adipose tissue is metabolically active and a major site of estrogen production. This itself poses potential to impact ovulation.
A small 2023 study examined the potential of semaglutide to modulate menstrual cycles in women with obesity and polycystic ovarian syndrome (PCOS). 80% of patients responsive to the drug demonstrated normalised menstrual cycles after 6 months, indicating the potential for GLP-1R agonists to modify fertility. Novo Nordisk stated they are gathering data to evaluate the safety of becoming pregnant whilst taking Wegovy. People who were pregnant or planned to become pregnant were excluded from the initial trials examining weight loss efficacy of Wegovy and Zepbound. As such, there is a lack of safety data on taking these drugs during pregnancy, and how this might affect foetal development.
The EMA label for Wegovy states that animal studies have indicated “reproductive toxicity”, advising against the use of the drug during pregnancy. More data are needed on the benefits and risks for using GLP-1R agonists around pregnancy, and these might be unveiled by various upcoming/ongoing research institution-sponsored trials, such as NCT05819853.?
Boehringer Ingelheim announces accelerated 10-year growth plan following a successful 2023
Boehringer Ingelheim has reported strong growth in 2023, with human pharmaceutical sales up 10.3% alongside an increase of EUR 5.2 billion in research and development investment. This growth, driven primarily by Jardiance sales, has repositioned Boehringer Ingelheim above Bayer as Germany’s largest pharmaceutical company.
Boehringer Ingelheim has seven disclosed potential anti-obesity assets which Airfinity are tracking. Four of these are in Phase I trials, two are in preclinical stages, whilst their lead compound, survodutide, is in Phase III trials for obesity and cardiovascular risk reduction, alongside demonstrating recent impressive data against MASH in Phase II. These assets will be critical to Boehringer Ingelheim’s recently announced 10-year growth plan.
Concern is growing over environmental impact of plastic waste from GLP-1 injectables
The continuing growth in the anti-obesity injectables market is putting pressure on drugmakers to ensure that plastic injection pens are recycled. Novo Nordisk runs a “PenCycle” scheme, in an attempt to minimise plastic wastage, through offering free recycling. As the market grows, the environmental impact of producing vast amounts of pens will likely become a wider concern. This may also feed into the promising oral market for anti-obesity drugs.
This week, Lexaria Biosciences announced the initiation of a pilot study of its oral candidate, “DehydraTECH-GLP-1”, which is a modified version of Novo Nordisk’s Rybelsus, which promises improved solubility, oral bioavailability and efficacy through the company’s proprietary drug delivery system (DehydraTECH).
Chinese regulators announce strong stance against covering weight loss drugs, whilst Lilly battles against drug shortages and compounding pharmacies in the US
A spokesperson from the National Healthcare Security Administration in China, announced this week that “China will definitely not include weight-loss drugs in its basic medical insurance no matter how magical they are”. China currently has two GLP-1R agonists approved for weight loss, both manufactured by local companies, Huadong Medicine and Benemae Pharmaceutical.
This strong stance from regulators does not bode well for wider coverage of Wegovy later in the year, when Novo Nordisk expects Chinese approval. In the US, Lilly are planning for a Zepbound label expansion, following the topline data disclosure from SURMOUNT-OSA. At the same time, the FDA are extending their warning for the shortage of Lilly’s Mounjaro from through April to through to June.
When drugs are deemed in shortage, specific pharmacies are authorised to make compounded versions of the drugs. In the case of GLP-1s this has typically been reported to involve using salt forms of the active substances semaglutide or tirzepatide, mixed with other molecules, such as vitamin B6. There are safety concerns about this unregulated, but legal, process with both Lilly and Novo Nordisk raising cases against compounding. This past week, Lilly suffered a legal loss in Florida in such a case.
News Highlights
领英推荐
Bloomberg - 17 April 2024
Eli Lilly - 17 April 2024
STAT News - 19 April 2024
Bloomberg - 16 April 2024
Medwatch - 17 April 2024
Endpoints News - 19 April 2024
Reuters - 15 April 2024
Seeking Alpha - 15 April 2024
BioSpace - 15 April 2024
BBC News - 17 April 2024
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