Novel drug candidate for slowing AAA growth demonstrates safety in humans

Stephen Cheng

The local delivery of a glucose-derived compound in small- and medium-sized abdominal aortic aneurysms (AAAs) has been deemed safe, with “promising” early efficacy data indicating its potential in stabilising or slowing AAA sac growth. According to Stephen Cheng (University of Hong Kong), these first-in-human study findings—which he presented at this year’s Society for Vascular Surgery (SVS) Vascular Annual Meeting (VAM 2023; 14–17 June, National Harbor, USA)—merit further evaluations within randomised controlled trials.

“The main message is that this is a group of patients where, currently, there are no effective treatments to slow the growth of [abdominal aortic] aneurysms,” Cheng tells Vascular News. “And, therefore, the idea of using a drug that is delivered only once inside the aneurysm sac sounds attractive— especially if it leaves nothing behind and all the future treatment options are left open.”

The multicentre study in question saw patients with an AAA (diameter <5.5cm) recruited to receive a one-time, local administration of 25ml of 1,2,3,4,6-pentagalloyl glucose (PGG) solution via transfemoral access. The study’s primary endpoints were technical success and safety—determined by the occurrence of major adverse events at 30 days. Cheng et al have reported a 100% rate of technical success, and found that the only safety-related concern was that four of the 21 enrolled patients showed a transient elevation of liver enzyme levels. However, these levels returned to normal within 30 days and triggered no clinical symptoms.

“When we talked to the pharma scientists, who are really looking at the molecular aspects of why these drugs work, the answer was that PGG is largely metabolised in the liver,” Cheng adds. “This is a way that the liver responds to any [raised level] of glucose in the metabolism pathway. That is the explanation that has been given to us, but we have seen no adverse effects in the patients. It will certainly be an area we will be closely monitoring as to how patients behave afterwards but, so far, they are all fine and the one patient who did have a very high enzyme level returned to normal in about a month’s time.” With this being a first-in-human study, Cheng is quick to point out that any conclusions drawn from the results regarding efficacy of the PGG solution in slowing AAA growth are preliminary.

Nevertheless, as per their secondary endpoint of freedom from aneurysm sac enlargement, the researchers report average AAA diameter changes from baseline of 0.2mm, 1.1mm, 2mm and 0.8mm at six, 12, 24 and 36 months, respectively. Follow-up computed tomography angiography (CTA) data further indicated average volume changes of 2.5%, 9.6%, 24.3%, and 11.6%, respectively—and, at 12 months, none of the aneurysms had grown by more than 5mm in diameter, while only three had a volume growth >10%.

Prior studies have indicated that the average rate of AAA sac growth is around 3–3.5mm per year, according to Cheng. He states that this figure was used as a target in the present study, adding that the treatment threshold in Caucasians is an aneurysm diameter of 5.5cm and, “if we can slow the growth by 50% [to about 1.7mm], then we can push back the threshold for intervention from five years to 10 years, and that would bring expected benefits”.

“But, I must reiterate that this is a first-in human study of a relatively small number of patients,” he adds. “The main focus was on patient safety rather than long-term aneurysm sac [growth].”


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