Lexaria Bioscience Says Drug Delivery Technology Reduces GLP-1 Drug Side Effects in Trial

 

• DehydraTECH-semaglutide reduces overall side effects by 36.5% as compared to Rybelsus®

• DehydraTECH-semaglutide reduces gastrointestinal side effects by 43.5% as compared to Rybelsus®

• DehydraTECH-GLP-1 study arms evidencing patient safety and tolerability consistent with the primary study endpoint

 Lexaria Bioscience Corp. (NASDAQ:LEXX)(NASDAQ:LEXXW) (the "Company" or "Lexaria"), a global innovator in drug delivery platforms, provides the following partial 8-week positive interim results update on the phase 1b, 12-week chronic study GLP-1-H24-4 (the "Study" or the "Lexaria Study"), currently underway in Australia, focusing on the DehydraTECH ("DHT") glucagon-like peptide-1 ("GLP-1") study arms 2 and 5 relative to the Rybelsus® control study arm 4.

"We are extremely encouraged by the interim results received to date aligned with our primary study endpoint," said Richard Christopher, CEO of Lexaria. "DehydraTECH is continuing to demonstrate obvious superiority in reducing unwanted side effects compared to the world's only approved oral-based GLP-1 medication, Rybelsus®."

Adverse Events

After 8 weeks of treatment, Lexaria's DehydraTECH-GLP-1 arms are tracking very nicely from a safety and tolerability perspective relative to the Rybelsus® control arm; most notably in terms of reductions in the incidence of gastrointestinal ("GI") adverse events ("AEs"):

GLP-1-H24-8-week Interim Results (Oral formulations)	DHT-semaglutide 3.5 mg x 4 weeks followed by 7 mg x 4 weeks (Arm 2; n=24)	Rybelsus® 3 mg x 4 weeks followed by 7 mg x 4 weeks (Arm 4; n = 25) (Study Control Arm)	DHT-tirzepatide 20 mg x 4 weeks followed by 40 mg x 4 weeks (Arm 5; n=25)
Persons with at least 1 AE	79.2%	100%	72.0%
Total AEs	61	96	90
Total AEs as a % of Control	63.5%	N/A	93.8%
Total GI AEs	26	46	20
Total GI AEs as a % of Control	56.5%	N/A	43.5%
Nausea	8	18	2
Vomiting	1	3	0
Diarrhea	5	6	9
All other GI AEs	12	19	9

n = number of patients included in each study group for safety and tolerability assessments

Of note, every person taking Rybelsus® in the Study experienced at least one AE. There was a 20.8% reduction in the overall number of persons experiencing an AE with DehydraTECH-semaglutide ("DHT-semaglutide") vs. Rybelsus® and a 36.5% reduction in the total quantity of AEs derived from DHT-semaglutide vs. Rybelsus®. There was also a 43.5% reduction in GI AEs from persons taking DHT-semaglutide vs. Rybelsus®.

In Novo Nordisk's® Semaglutide Treatment Effect in People with obesity (STEP) studies, across a patient population of 3,331 people, 2,934 or 88.1% of them experienced AEs of any kind. Through 8 weeks, only 79.2% of patients in the DHT-semaglutide study arm have experienced AEs of any kind, meaning 10.1% fewer patients in the DHT-semaglutide study arm experienced AEs relatively speaking. Potentially removing all AEs from 10% of a patient population that is currently millions of people, could provide immense relief for many and encourage more people to continue on their treatment protocol without premature discontinuation as is often a challenge commercially today due to unwanted AEs.

It is difficult to compare the DehydraTECH-tirzepatide ("DHT-tirzepatide") AEs to any benchmark because there is no commercially available orally-dosed tirzepatide sold today, as tirzepatide is sold by Eli Lilly only in injectable formats. A meta-analysis reviewing 10 different injected tirzepatide trials involving 6,836 patients found broadly similar incidences of AEs as did the Lexaria Study examining orally dosed DHT-tirzepatide, but that meta-analysis noted that 40% to 50% of injected tirzepatide AEs were GI-related, whereas for the DHT-tirzepatide study arm that proportion of GI-related AEs through 8 weeks is much lower at 22%. This could potentially signify that oral DHT-tirzepatide might reduce AEs by as much as half, compared to the injectable tirzepatide that was evaluated in those earlier studies.

HbA1c and Bodyweight

Assessments of the magnitude of decreases in glycated haemoglobin ("HbA1c"), as a primary blood test for blood sugar levels, and body weight are the major efficacy endpoints of the Study.

For comparison purposes, in Novo Nordisk's® Pioneer 1 phase 3a randomized study conducted in 703 patients with type 2 diabetes, daily doses of Rybelsus® semaglutide were administered at varying dose levels, and, after 26 weeks of dosing, the average changes in HbA1c levels and body weight were reported as follows:

Pioneer 1: 26-Week Final Results	3 mg Rybelsus®	7 mg Rybelsus®	14 mg Rybelsus®
Body Weight Baseline = 88.1kg	-1.32 kg or -1.5%	-2.02 kg or -2.3%	-3.26 kg or -3.7%
HbA1c	-0.9%	-1.2%	-1.4%

Further, Novo Nordisk's® Pioneer 6 phase 3a randomized study conducted in 1,591 patients received daily doses of Rybelsus® administered at 3 mg for the first 4 weeks; 7 mg for the next 4 weeks; and 14 mg thereafter until the conclusion of the study. As such the Pioneer 6 study utilized a dose escalation strategy nearly identical to the Lexaria Study for the first 8 weeks thereof at least, with average results shown in the table below:

Pioneer 6: 8-Week Approximate ** Interim Results	Rybelsus® 3 mg x 4 weeks followed by 7 mg x 4 weeks
Body Weight Baseline = 91.0 kg	-1.70 kg or 1.9%
HbA1c	-0.825%

**8-week results from Pioneer 6 study have been extrapolated from the study appendix

In the context of this press release it is very important to remember that Lexaria is, today, only reporting interim average 8-week results which is clearly a small fraction of the time studied relative to the above noted Pioneer 1, 26-week study, therefore making Lexaria's Study results more relatable to the Pioneer 6, 8-week study interim results data:

GLP-1-H24-4 8-week Interim Results	DHT-semaglutide 3.5 mg x 4 weeks followed by 7 mg x 4 weeks (Arm 2; n=23)	Rybelsus® 3 mg x 4 weeks followed by 7 mg x 4 weeks (Arm 4; n=25) (Study Control Arm)	DHT-tirzepatide 20 mg x 4 weeks followed by 40 mg x 4 weeks (Arm 5; n=24)
Body Weight	-1.14 kg or -1.23% (range -6.6 to + 4.6 Kg)	-4.14 kg or -4.23% (range -8.9 to +0.0 Kg)	+0.28 kg or +0.28% (range -8.0 to +7.0 Kg)
HbA1c	-0.14% (range -0.5 to +0.3%)	-0.25% (range -0.6 to +0.5%)	+0.01% (range -0.5 to +0.5%)

n = number of patients included in each study group for HbA1c and body weight efficacy assessments

Lexaria's average DHT-semaglutide weight loss results after 8 weeks are tracking similar to the historical performance of Rybelsus® in the much larger Pioneer studies, which is thus far encouraging to see.

Curiously, the Rybelsus® body weight performance data in the current Lexaria Study appears to be much stronger than the results shown above in both the 26-week Pioneer 1 study and in the Pioneer 6, 8-week interim data. The reasons for this apparent anomaly are presently unknown, but likely related to the small sample size of the Lexaria Study. The historical studies conducted in thousands of persons are more likely to be representative of real-world performance.

For HbA1c levels it is important to understand that HbA1c measures blood glucose over a 8-12 week period of time, thus the current 8-week data from Lexaria's Study is barely relevant compared to expected 12-week data. Furthermore, there is no statistically significant difference between the DHT-semaglutide and Rybelsus® reductions in HbA1c witnessed at the 8-week point thus far in the Study (p=0.069). The 12-week HbA1c data should be more representative, and potentially, quite different from the 8-week data.

Additional 8-week interim Study data may or may not be released as it is more fully processed and understood in the weeks to come. The vast majority of laboratory-derived data, including a battery of additional safety, tolerability and efficacy parameter assessments beyond those summarized here, and all final results will not be available until near the end of calendar-2025. The Study is currently approaching the "last patient last visit" milestone and remains on schedule.

https://www.morningstar.com/news/accesswire/1053185msn/lexaria-provides-positive-interim-results-on-partial-8-week-data-from-phase-1b-glp-1-h24-4-study