LEXXW - Lexaria's Technology Improves the Oral Performance of the Rybelsus-Branded GLP-1 drug Semaglutide in Human Pilot Study
(TheNewswire)
DehydraTECH TM -powered semaglutide achieved thesebenefits in a human pilot study compared to Rybelsus ® :
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Sustained higher levels ofsemaglutide in blood;
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Faster achievement of peak drugdelivery; and
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Reduced side effects.
Kelowna, British Columbia – TheNewswire - November 27, 2023 –Lexaria Bioscience Corp. (Nasdaq:LEXX )( Nasdaq:LEXXW) (the “Company” or“Lexaria”), a global innovator in drug delivery platformsannounces positive interim results from a human pilot study (the“ Study ”) currently underway evaluating DehydraTECH TM technology forthe oral delivery of the glucagon-like peptide-1 (“ GLP-1 ”) drugsemaglutide available commercially in the branded product Rybelsus®.
The Study is being performed by a prominent universityresearch center comparing a single 7 mg semaglutide dose of a Rybelsustablet (“ Control ”) to a matching dose from Rybelsus that had been compoundformulated in capsule form using DehydraTECH processing technologyenhancements (“ DehydraTECHGLP-1 ”).
Blood Levels of Semaglutide
Blood was examined by a third-party laboratory using avalidated bioassay 18 times over the first 10 hours of the Study, andonce again 24 hours after the dose was administered. Subjects weresupervised and monitored in the Study site over the entire 10-hourduration post dosing, and then allowed to depart, resume normalactivities and return to the Study site the following day forperformance of the 24-hour evaluation time point. The firstpost-baseline blood was sampled 20 minutes after oral administrationand, at that point in time, the DehydraTECH GLP-1 blood semaglutidelevel was ~125% higher than that of the Control. At each of the 19blood sample time points, the DehydraTECH GLP-1 blood semaglutidelevels were higher than the Control levels. Furthermore, theDehydraTECH GLP-1 peak was achieved faster at 120 minutes (as comparedto 160 minutes for the Control) and with a 16% higher bloodsemaglutide level than the Control. Of note, the blood semaglutidelevels achieved with the Control were proportional to those achievedby other researchers in similar single dose cross-over Rybelsus developmentinforming studies, further suggesting that the blood semaglutide levelgains evidenced by the DehydraTECH GLP-1 formulation were notablydistinct relative to the commercial product.
Blood Semaglutide Levels
Rybelsus ( blue ) 7mg (n=3) DehydraTECH ( orange ) GLP-1 7mg (n=4)
Interestingly, even 24 hours after dose administration,the DehydraTECH GLP-1 blood semaglutide levels were stillapproximately 25% higher than the Control levels (Note - only thefirst 10 hours post dosing is shown in the graph above). Overall,the total semaglutide drug quantity based on the area under the curveor “AUC” delivered by the two interventions over the course of the24 hour Study monitoring period was approximately 15% higher in thecase of the DehydraTECH-GLP-1 versus that of the Control.
Side Effects
Two of the three Control subjects and zero of the fourDehydraTECH GLP-1 subjects reported experiencing moderate nausea. Allthree Control subject reported experiencing mild nausea at both the2-hour and 10-hour timepoints whereas only one DehydraTECH GLP-1subject reported mild nausea and only at the single, 2-hour timepoint.
Ongoing and Future Work
This Study is only meant to provide early-stageindicative information to Lexaria about the possibility of enhancingthe pharmacokinetic (“PK”) and pharmacodynamic performance oforally delivered GLP-1 drugs to assist in guiding the Lexaria team inadditional investigations.
This Study is not complete and additional results willbe reported, likely in two tranches: Lexaria has also collected bloodglucose data and expects to release those interim results imminently.Then, once the cross-over Study visit as described below has beenconducted, final results from the Study should be available in lateDecember or early January. Given the smallsample size of this Study, it was not sufficiently powered forstatistical significance analysis, which will be a key part of anyexpanded studies with DehydraTECH GLP-1 undertaken in thefuture.
Parallel to Lexaria’s 2021 optimization program withDehydraTECH-processed cannabidiol (“CBD”), where the formulationutilized in the animal study DIAB-A22-1 demonstrated 364%higher (p=0.0002) PK performance thanLexaria’s original DehydraTECH-CBD formulations, we expect to createseveral different DehydraTECH GLP-1 formulations to explore deliveryand performance optimization of semaglutide. As seen with our pastDehydraTECH-CBD advancements, Lexaria willendeavor to similarly improve performance of future DehydraTECH-GLP-1formulations.
Lexaria has demonstrated in many previous R&Dprograms, including five human clinical studies, that DehydraTECH cangreatly improve the PK performance of many orally administered drugsinto the bloodstream. Like many of these agents, GLP-1 drugs also exhibit very poor oralbioavailability (as little as 0.8%) withoutthe use of absorption enhancement technology, such as Lexaria’sDehydraTECH. As noted above, DIAB-A22-1 evidenced DehydraTECH-CBD lowering body weight over a sustaineddosing period by 7%, and also lowered blood sugar and triglyceridelevels.
Design has already begun of a comprehensive animal PKand efficacy modelling study program to pursue these goals usingdifferent DehydraTECH compositions and different GLP-1 drug molecules.The Company cannot know in advance whether future formulations willperform better or worse than that which was used in the current Study.We are currently planning to begin the DehydraTECH-GLP-1 animal studyduring Q1, 2024.
Separately, Lexaria is also exploring the possibilityof studying DehydraTECH-GLP-1 in a multi-week human clinical trial toexamine both diabetes-related control (in part via reduced blood sugarlevels) as well as weight loss following treatment. If designparameters allow, we intend to test, separately, DehydraTECH-GLP-1, aswell as a combination of DehydraTECH-CBD with DehydraTECH GLP-1, basedon the noteworthy effects of DehydraTECH-CBD evidenced in animal studyDIAB-A22-1. Before proceeding with this human evaluation, we hope tohave the animal formulation PK and efficacy modelling test results sothat we can use the best-performing formulation in the multi-weekhuman clinical trial. Thus, all things being favourable, we expectthe multi-week human clinical trial could start near the end of Q2 orsometime in Q3, 2024.
Execution of the above-described animal study andmulti-week human clinical trial will be contingent on raisingadditional capital necessary to fund doing so. Through theseexpanded studies, Lexaria hopes to achieve superior PK performanceusing DehydraTECH-powered GLP-1 drugs which could enable drug deliveryvia oral capsule at lower costs than current injectables, with reducedside effects and enhanced health benefits. Ultimately, Lexaria’sgoal in doing so will be to demonstrate advancements worthy ofcommercial product development and potential pharmaceutical industrystrategic partnering interest, for superior performing oral GLP-1drugs as more viable and attractive alternatives to the injectableformat.
About the Study
The Study was performed to provide an early-stageindication of whether DehydraTECH processing could improve oral drug delivery characteristics of the GLP-1 drug semaglutide sold asRybelsus. A single semaglutide dose of 7 mg of the Rybelsus Controlwas compared to the matching dose of the DehydraTECH GLP-1, swallowedby each subject after an overnight fasting period together with a 50mL glass of water. The DehydraTECH GLP-1 formulation used in thisStudy was compound formulated strictly for research purposes. Sevenhealthy subjects were dosed, four of whom received the DehydraTECHGLP-1, and three of whom received the Control. These seven subjectsare expected to return to the Study site in December to be dosed asecond time in the reverse order following the “cross-over” designof this Study to ensure that all seven subjects will have been treatedwith both the Control and DehydraTECH GLP-1 treatments over the courseof the two visits.
About GLP-1 Drugs .
Rybelsus (semaglutide) is the only GLP-1 drug approved by theFDA for oraldosing to treat diabetes and weight loss. TheFDA has also approved semaglutide marketed as Ozempic ® and Wegovy ® , administered by injection , to treat diabetes and weight loss. All three of these drugsare owned and manufactured by Novo Nordisk.
GLP-1 drugs have recently been approved by the FDA fortype two diabetes and weight loss management. Weight loss of between 10 pounds to 33pounds , or more, has been widely reported.One 68-week study of 667 people reported an average loss of 15% of bodyweight .
Anecdotal commentary also suggests that some patientsare experiencing reduced cravings for alcohol, nicotineand opioids while taking GLP-1 drugs. Othertrials are examining their effects on heart disease and evendementia in part because of evidence thatGLP-1 drugs may reduce the build-up of the proteins amyloid and tau inthe brain, thought to be partly responsible for Alzheimer’sdisease.
Side effects of GLP-1drugs vary but can include nausea, vomiting,diarrhea and more. A small number of GLP-1 drugs have already beentested or approved in oral format but some studies have reported worse sideeffects with the oral form . The drugs arealso being investigated for their relationship to bone density, muscleloss and more. Because of potential serious side effects, it may bebeneficial to treat patients with lower oral doses of the drugs,something that Lexaria’s DehydraTECH technology may enable if it canimprove the PK performance of GLP-1 drugs through oralcapsules.
Because GLP-1 drugs have experienced FDA approvals asrecently as 2021 and 2022, and because the health benefits of thisdrug class are still being discovered and understood, the potentialmarket size is unknown. Published reports are widely estimating $100billion in sales per year, by 2030. At least one analyst fromGuggenheim Partners published a note on September 12, 2023 in which he explained how “the totaladdressable market for these so-called incretin drugs could balloon to $150 billion to $200billion .”
About DehydraTECH
DehydraTECH is a patented drug delivery formulation andprocessing platform technology Lexaria has developed and isinvestigating for a variety of beneficial molecules. DehydraTECH isdesigned to improve the way active molecules enter the bloodstreamupon oral ingestion. DehydraTECH has also demonstrated enhanceddelivery of certain active molecules into brain tissue, which Lexariabelieves to be of particular importance for centrally activecompounds. Lexaria has also developed DehydraTECH formulations forother applications demonstrating superior bio-absorption whenadministered intraorally and topically.
About Lexaria Bioscience Corp.
Lexaria Bioscience Corp.’s patented drug deliverytechnology, DehydraTECH™, improves the way active pharmaceuticalingredients (APIs) enter the bloodstream through oral delivery. Since2016, DehydraTECH has repeatedly demonstrated the ability to increasebio-absorption with cannabinoids, antiviral drugs, PDE5 inhibitors andmore. DehydraTECH has also evidenced an ability to deliver some drugsmore effectively across the blood brain barrier. Lexaria operates alicensed in-house research laboratory and holds a robust intellectualproperty portfolio with 37 patents granted andmany patents pending worldwide. For more information, please visit www.lexariabioscience.com .
CAUTION REGARDING FORWARD-LOOKINGSTATEMENTS
This press release includes forward-looking statements.Statements as such term is defined under applicable securities laws.These statements may be identified by words such as"anticipate," "if," "believe,""plan," "estimate," "expect,""intend," "may," "could,""should," "will," and other similar expressions.Such forward-looking statements in this press release include, but arenot limited to, statements by the Company relating to the Company’sability to carry out research initiatives, receive regulatoryapprovals or grants or experience positive effects or results from anyresearch or study. Such forward-looking statements are estimatesreflecting the Company's best judgment based upon current informationand involve a number of risks and uncertainties, and there can be noassurance that the Company will actually achieve the plans,intentions, or expectations disclosed in these forward-lookingstatements. As such, you should not place undue reliance on theseforward-looking statements. Factors which could cause actual resultsto differ materially from those estimated by the Company include, butare not limited to, government regulation and regulatory approvals,managing and maintaining growth, the effect of adverse publicity,litigation, competition, scientific discovery, the patent applicationand approval process, potential adverse effects arising from thetesting or use of products utilizing the DehydraTECH technology, theCompany’s ability to maintain existing collaborations and realizethe benefits thereof, delays or cancellations of planned R&D thatcould occur related to pandemics or for other reasons, and otherfactors which may be identified from time to time in the Company'spublic announcements and periodic filings with the US Securities andExchange Commission on EDGAR. The Company provides links tothird-party websites only as a courtesy to readers and disclaims anyresponsibility for the thoroughness, accuracy or timeliness ofinformation at third-party websites. There is no assurance that any ofLexaria’s postulated uses, benefits, or advantages for the patentedand patent-pending technology will in fact be realized in any manneror in any part. No statement herein has been evaluated by the Food andDrug Administration (FDA). Lexaria-associated products are notintended to diagnose, treat, cure or prevent any disease. Anyforward-looking statements contained in this release speak only as ofthe date hereof, and the Company expressly disclaims any obligation toupdate any forward-looking statements or links to third-party websitescontained herein, whether as a result of any new information, futureevents, changed circumstances or otherwise, except as otherwiserequired by law.
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