Glucagon-like peptide 1 (GLP-1) agonists have proven their therapeutic mettle in treating metabolic diseases like diabetes and obesity, and now, researchers are studying their effects on cardiovascular disease.
These drugs mimic glucagon-like peptide 1, a hormone that stimulates insulin production in the body. So, when blood sugar levels are elevated – particularly after eating – GLP-1 agonists spur insulin production leading to lower blood sugar levels, which is ultimately beneficial for controlling type 2 diabetes. Although how exactly these drugs help in weight loss is not known, as GLP-1 agonists slow the movement of food traveling from the stomach to the small intestine, it makes people feel full quicker and for longer, and so, it is thought to boost weight loss because people tend to eat less as result of the medication.
Altimmune’s GLP-1 agonist in the clinic
Some biotechs think that by broadening the therapeutic scope of GLP-1 agonists, cardiovascular diseases can be addressed. One such company that is looking to do so is Altimmune. The American clinical-stage GLP-1 specialist is the maker of pemvidutide, which is being evaluated in phase 2 trials for obesity and nonalcoholic steatohepatitis (NASH).
The results from a 48-week phase 2 trial in patients with obesity who are at risk of developing cardiovascular diseases, showed that patients had achieved a mean weight loss of 15.6% on a 2.4 mg dose of the drug, and notably, improvements in blood pressure as well as no cardiac event imbalances took place.
“We believe the magnitude of weight loss, robust reductions in triglycerides, LDL (low-density lipoprotein) cholesterol and blood pressure, together with the safety profile observed in this trial, could potentially differentiate pemvidutide from the other incretin-based therapies,” said Vipin K. Garg, president and chief executive officer of Altimmune, in a press release two months ago. “If approved, we believe pemvidutide could offer an important option for obesity patients, including those with risk factors for cardiovascular disease.”
However, tolerability issues remain, as the trial led to one participant experiencing vomiting, and 4.1% of the patients in the drug cohort discontinuing treatment in the first 16 weeks, when compared to 2.1% in the placebo group.
Can Wegovy’s GLP-1 treat cardiovascular diseases?
Altimmune’s pemvidutide trial intends to give competition to Novo Nordisk’s Wegovy (semaglutide), which received the U.S. Food and Drug Administration (FDA) nod to treat obesity two years ago. Now, the Danish pharma giant could be onto something bigger as it has hinted that Wegovy could even reduce the risk of heart attack in some patients.
While weight loss has been linked to improving metabolic activity and heart pumping, as heart tissue and the walls of the blood vessels get thinner, and levels of cholesterol and triglyceride levels are known to become more stable, Novo Nordisk has claimed that Wegovy’s heart health benefits go beyond the effects of weight loss, at the American Heart Association (AHA) Scientific Sessions in the U.S., that took place in November.
In the phase 3 SELECT trial of Wegovy, the drug lowered major adverse cardiovascular events (MACEs) by 20%. Moreover, the drug reduced the risk of cardiac-related death in patients with obesity and cardiovascular disease by 15%, and the risk of developing diabetes – all the patients in the trial were diabetes-free – by 73%.
To add to that, the STEP HFpEF trial conducted by Novo Nordisk showed that semaglutide could cut down the risk of heart failure. The study, which tested the drug in 529 patients with obesity and heart failure with preserved ejection fraction (HFpEF), demonstrated a 16.6-point increase at 52 weeks, with regard to the Clinical Summary Score (CSS) on the Kansas City Cardiomyopathy Questionnaire (KCCQ) – a measure of symptoms of heart failure – in comparison to an 8.7-point increase in the placebo group. HFpEF is a syndrome in which patients experience symptoms of heart failure due to the stiffening of the muscle in the left ventricle, which thereby leads to high filling pressure. So, in this case, the jump in points on the CSS score represents clinical improvement in HFpEF.
The trial results enable the pharmaceutical to pursue regulatory approval to be able to commercialize the drug for cardiovascular-related indications.
However, the weight loss maker, which also sells semaglutide for type 2 diabetes under the brand name Ozempic, has been under scrutiny for its pricing of Wegovy, which stands at $1,349 for a pack of four injection pens in the U.S. for those who do not have insurance coverage, an expense that is more than four times its cost in Germany. Besides, the cost deters it from making its way into low- and middle-income countries, where people are not only most affected by obesity, but are also at risk of cardiovascular death, where it makes up nearly 80% of the global burden, according to the National Institutes of Health. Yet, the company stated back in June, that it would take a while until the drug is launched in other countries, owing to soaring demand and infrastructure challenges like insufficient cold chain technology.
Another contender to Wegovy is Eli Lilly’s Zepbound, another GLP-1 receptor agonist for obesity that was welcomed by the FDA in November. However, in the case of cardiovascular indications, Wegovy seems to have the upper hand, as Zepbound hasn’t demonstrated cardiovascular benefit yet. Nevertheless, the GLP-1 receptor agonist has been prescribed for people with obesity who have weight-related cardiovascular disease.
GLP-1 agonists, not the only drugs to address more than one indication
This is not the first time that a drug has been used for several indications. For instance, bupropion, most popularly sold under the brand name Wellbutrin, has been greenlit to treat adult depression and seasonal affective disorder, as well as to support smoking cessation. Similarly, birth control pills mainly function to prevent pregnancy, but can also help alleviate endometriosis pain. And more commonly, pain relief medication aspirin can act as a blood thinner and lower blood clotting, and thereby prevent a heart attack. Several onco-drugs have also been designated to target multiple cancers.
So, it may be of little surprise that GLP-1 agonists could be used to address other metabolic disorders, apart from diabetes and obesity, like cardiovascular diseases. Furthermore, a research paper published in Frontiers in Pharmacology in 2022, suggests that GLP-1 agonists can “exert antiatherosclerotic and vasodilatory effects in epicardial coronary arteries” and improve coronary microvascular function (CMF). Coronary atherosclerosis is a coronary artery disease that is caused by elevated amounts of cholesterol deposits, resulting in plaque buildup in the walls of the coronary arteries – which supply blood to the heart. So, its impact on heart health seems to be encouraging, based on current research.
Nevertheless, the need for larger trials that are streamlined towards examining its therapeutic abilities for cardiovascular illnesses, exists. And whether this class of drugs manages to woo drug regulators, we will have to be on the lookout for, in the coming months.