Amylyx Pharmaceuticals Announces Pivotal Phase 3 LUCIDITY Trial Design for GLP-1 Receptor Antagonist (Avexitide) in Post-Bariatric Hypoglycemia
Amylyx Pharmaceuticals (AMLX) has announced the design of its pivotal Phase 3 LUCIDITY trial for avexitide, a first-in-class GLP-1 receptor antagonist for treating post-bariatric hypoglycemia (PBH). The trial will evaluate the reduction in hypoglycemia events as the primary outcome, with the first participant expected to be dosed in Q1 2025 and topline results in 2026.
The trial will involve approximately 75 participants across 20 U.S. sites, randomized 3:2 to receive either 90 mg avexitide or placebo. The study includes a three-week run-in period and a 16-week treatment period, followed by a 32-week open-label extension. Previous Phase 2 trials showed significant reductions in hypoglycemia events, with the Phase 2b trial demonstrating a 53% reduction in Level 2 and 66% reduction in Level 3 hypoglycemia events.
Amylyx Pharmaceuticals (AMLX) ha annunciato la progettazione del suo fondamentale trial di Fase 3 LUCIDITY per avexitide, un antagonista del recettore GLP-1 di prima generazione per il trattamento dell'ipoglicemia post-bariatrica (PBH). Il trial valuterà la riduzione degli eventi ipoglicemici come risultato principale, con il primo partecipante previsto per essere trattato nel primo trimestre del 2025 e risultati preliminari attesi nel 2026.
Il trial coinvolgerà circa 75 partecipanti in 20 siti negli Stati Uniti, randomizzati in un rapporto di 3:2 per ricevere 90 mg di avexitide o un placebo. Lo studio include un periodo di preparazione di tre settimane e un periodo di trattamento di 16 settimane, seguito da un'estensione open-label di 32 settimane. I precedenti trial di Fase 2 hanno mostrato significative riduzioni negli eventi ipoglicemici, con il trial di Fase 2b che ha dimostrato una riduzione del 53% negli eventi di ipoglicemia di Livello 2 e del 66% negli eventi di Livello 3.
Amylyx Pharmaceuticals (AMLX) ha anunciado el diseño de su importante ensayo de Fase 3 LUCIDITY para avexitide, un antagonista del receptor GLP-1 de primera clase para el tratamiento de la hipoglucemia post-bariátrica (PBH). El ensayo evaluará la reducción de los eventos hipoglucémicos como resultado primario, con el primer participante previsto para ser dosificado en el primer trimestre de 2025 y resultados preliminares en 2026.
El ensayo involucrará aproximadamente a 75 participantes en 20 sitios en EE. UU., aleatorizados en una proporción de 3:2 para recibir 90 mg de avexitide o un placebo. El estudio incluye un período de preparación de tres semanas y un período de tratamiento de 16 semanas, seguido de una extensión abierta de 32 semanas. Ensayos previos de Fase 2 mostraron reducciones significativas en los eventos hipoglucémicos, con el ensayo de Fase 2b demostrando una reducción del 53% en eventos de hipoglucemia de Nivel 2 y del 66% en eventos de Nivel 3.
Amylyx Pharmaceuticals (AMLX)는 3상 LUCIDITY 시험의 설계를 발표했습니다. 이는 bariatric surgery 후 저혈당증 (PBH) 치료를 위한 첫 번째 GLP-1 수용체 길항제인 avexitide에 대한 것입니다. 이 시험은 주요 결과로 저혈당 사건의 감소를 평가할 것이며, 첫 번째 참가자는 2025년 1분기에 투여될 것으로 예상되며 topline 결과는 2026년에 발표될 것입니다.
이 시험은 약 75명의 참가자를 포함하고 미국의 20개 사이트에서 실시됩니다. 참가자는 3:2 비율로 90 mg의 avexitide 또는 위약을 받도록 무작위 배정됩니다. 이 연구는 3주간의 준비 기간과 16주간의 치료 기간을 포함하며, 이후 32주간의 공개 연장 기간이 진행됩니다. 이전의 2상 시험에서는 저혈당 사건의 유의미한 감소가 나타났으며, 2b상 시험에서는 2단계 저혈당 사건이 53% 감소하고 3단계 저혈당 사건이 66% 감소했습니다.
Amylyx Pharmaceuticals (AMLX) a annoncé la conception de son essai décisif de Phase 3 LUCIDITY pour l'avexitide, un antagoniste du récepteur GLP-1 de première classe pour le traitement de l'hypoglycémie post-bariatique (PBH). L'essai évaluera la réduction des événements hypoglycémiques comme principal critère d'évaluation, avec le premier participant prévu pour être traité au premier trimestre 2025 et des résultats préliminaires attendus en 2026.
L'essai impliquera environ 75 participants dans 20 sites aux États-Unis, randomisés dans un rapport de 3:2 pour recevoir soit 90 mg d'avexitide soit un placebo. L'étude comprend une période d'initiation de trois semaines et une période de traitement de 16 semaines, suivie d'une extension en ouvert de 32 semaines. Les précédents essais de Phase 2 ont montré des réductions significatives des événements hypoglycémiques, l'essai de Phase 2b montrant une réduction de 53% des événements d'hypoglycémie de Niveau 2 et de 66% des événements de Niveau 3.
Amylyx Pharmaceuticals (AMLX) hat das Design seiner entscheidenden Phase 3 LUCIDITY-Studie für Avexitide, einen GLP-1-Rezeptor-Antagonisten der ersten Klasse zur Behandlung der postbariatrischen Hypoglykämie (PBH), bekannt gegeben. Die Studie wird die Reduktion von Hypoglykämie-Ereignissen als primäres Ergebnis bewerten, wobei der erste Teilnehmer voraussichtlich im ersten Quartal 2025 behandelt wird und die vorläufigen Ergebnisse im Jahr 2026 erwartet werden.
Die Studie wird etwa 75 Teilnehmer an 20 Standorten in den USA umfassen, die im Verhältnis 3:2 randomisiert werden, um entweder 90 mg Avexitide oder ein Placebo zu erhalten. Die Studie umfasst eine dreimonatige Vorbereitungsphase und eine 16-wöchige Behandlungsphase, gefolgt von einer 32-wöchigen offenen Verlängerung. Frühere Phase-2-Studien zeigten signifikante Reduktionen bei Hypoglykämie-Ereignissen, wobei die Phase-2b-Studie eine Reduktion von 53% bei Level-2- und 66% bei Level-3-Hypoglykämie-Ereignissen ergab.
- Avexitide has received FDA Breakthrough Therapy and Orphan Drug Designations
- Phase 2b trial showed 53% reduction in Level 2 and 66% reduction in Level 3 hypoglycemia events
- Consistent positive results across five clinical trials
- Clear development timeline with topline results expected in 2026
- Phase 3 trial won't start until Q1 2025, indicating a lengthy timeline to potential commercialization
- Small trial size of only 75 participants may raise questions about statistical power
Insights
This pivotal Phase 3 LUCIDITY trial announcement represents a significant milestone for Amylyx's avexitide program. The trial design incorporates several promising elements: 75 participants randomized 3:2 with a robust 16-week treatment period, followed by a 32-week open-label extension. The trial builds upon compelling Phase 2 data showing
The FDA Breakthrough Therapy and Orphan Drug Designations highlight the unmet medical need in post-bariatric hypoglycemia. The trial's focus on an FDA-agreed primary endpoint of hypoglycemia event reduction strengthens the regulatory pathway. Previous Phase 2 results demonstrating
The Q1 2025 trial initiation timeline with topline data expected in 2026 sets clear development milestones. With no currently approved treatments for PBH, positive Phase 3 results could position avexitide as a first-in-class therapy in this orphan indication.
- Pivotal Phase 3 LUCIDITY trial will evaluate FDA-agreed upon primary outcome of reduction in hypoglycemia events and designed to align as closely as possible with previous Phase 2 trial designs
- Amylyx expects first study participant dosed in LUCIDITY in Q1 2025 and topline results in 2026
- Avexitide has FDA Breakthrough Therapy Designation for the treatment of post-bariatric hypoglycemia and Orphan Drug Designation
- Amylyx to present the Phase 3 LUCIDITY trial design at the World Congress on Insulin Resistance, Diabetes & Cardiovascular Disease on December 12-14
“We are excited to advance avexitide into a Phase 3 clinical trial, marking a pivotal step toward bringing this investigational therapy to people living with PBH,” said Joshua Cohen and Justin Klee, Co-CEOs of Amylyx. “The consistent data from five clinical trials of avexitide in PBH underscore avexitide’s potential to be the first therapy approved for people living with PBH.”
LUCIDITY will be a multicenter, randomized, double-blind, placebo-controlled Phase 3 clinical trial evaluating the efficacy and safety of avexitide in participants with PBH following Roux-en-Y gastric bypass (RYGB) surgery. The Phase 3 trial will be conducted at approximately 20 sites in the
“PBH is believed to result from an excessive GLP-1 response leading to persistent, recurrent, and debilitating hypoglycemia events that take a profound toll on someone’s quality of life. Avexitide is designed to bind to the GLP-1 receptor and inhibit the effects of excessive GLP-1 in PBH, mitigating hypoglycemia by decreasing insulin secretion and stabilizing blood glucose levels. We are excited to evaluate avexitide, which has FDA Breakthrough Therapy and Orphan Drug Designations, in the Phase 3 LUCIDITY trial, following two Phase 2 clinical studies that demonstrated compelling clinical data supporting avexitide’s ability to significantly reduce the rates of hypoglycemia events,” said Camille L. Bedrosian, MD, Chief Medical Officer of Amylyx. “Our goal in Phase 3 is to align the trial design as closely as possible with the prior studies. Importantly, we believe LUCIDITY is well powered to detect a treatment effect. We look forward to continuing to collaborate with study investigators and the PBH community as we seek to initiate LUCIDITY and advance avexitide through the clinical development process.”
LUCIDITY was informed by data from five clinical trials of avexitide in people with PBH showing consistent, dose-dependent effects across studies. The five clinical trials include a Phase 1 trial, a single ascending dose trial, a multiple ascending dose trial, and two Phase 2 trials:
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In the Phase 2 (PREVENT), 28-day, randomized, placebo-controlled crossover trial (N=18), results showed a significant reduction in rates of Level 2 and 3 hypoglycemia events in participants with PBH after RYGB surgery following treatment with 30 mg twice daily and 60 mg once daily of avexitide compared with placebo. PREVENT’s primary endpoint was met with statistical significance, showing both avexitide dosing regimens improved the lowest glucose level (nadir) after a meal as measured during formal mixed meal tolerance testing (MMTT). Mean plasma glucose nadir was increased by
21% (p=0.001) and26% (p=0.0002) following avexitide 30 mg twice daily and 60 mg once daily dosing, respectively, compared to placebo. -
In the Phase 2b, 28-day, open-label, investigator-initiated, crossover trial (N=16), 90 mg once daily and 45 mg twice daily of avexitide met its primary endpoint and significantly reduced rates of hypoglycemia events in participants following RYGB surgery and other upper-gastrointestinal surgeries. Participants in the Phase 2b trial receiving 90 mg once daily of avexitide, the dose Amylyx plans to evaluate in LUCIDITY, saw a statistically significant
53% reduction in Level 2 hypoglycemia events (p=0.004) and a statistically significant66% reduction in Level 3 hypoglycemia events (p=0.0003).
Avexitide was generally well tolerated, with a favorable safety profile replicated across the clinical trials.
Amylyx will present the trial design at the World Congress on Insulin Resistance, Diabetes & Cardiovascular Disease (WCIRDC) in
About Avexitide
Avexitide is an investigational, first-in-class glucagon-like peptide-1 (GLP-1) receptor antagonist that has been evaluated in five clinical trials for post-bariatric hypoglycemia (PBH) and has also been studied in congenital hyperinsulinism (HI). The
About Post-Bariatric Hypoglycemia (PBH)
Symptomatic post-bariatric hypoglycemia (PBH) is a condition that affects approximately
About Amylyx Pharmaceuticals
Amylyx is committed to the discovery and development of new treatment options for communities with high unmet needs, including people living with serious and fatal neurodegenerative diseases and endocrine conditions. Since its founding, Amylyx has been guided by science to address unanswered questions, keeping communities at the heart and center of all decisions. Amylyx is headquartered in
Forward-Looking Statements
Statements contained in this press release and related comments in our earnings conference call regarding matters that are not historical facts are “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995, as amended. Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. Such statements include, but are not limited to, the potential of avexitide as a treatment for PBH; expectations regarding the timing of initiation of a Phase 3 trial of avexitide in PBH and the timing of results from the trial; and expectations regarding the potential for the results of a Phase 3 trial to support approval of avexitide; the Company’s expectations regarding its financial performance; and expectations regarding the Company’s cash runway and longer-term strategy. Any forward-looking statements in this press release and related comments in the Company's earnings conference call are based on management’s current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. Risks that contribute to the uncertain nature of the forward-looking statements include: the success, cost, and timing of Amylyx’ program development activities; Amylyx’ ability to execute on its regulatory development plans and expectations regarding the timing of results from its planned data announcements and initiation of clinical studies; the risk that early-stage results may not reflect later-stage results; Amylyx’ ability to fund operations, and the impact that global macroeconomic uncertainty, geopolitical instability, and public health events will have on Amylyx’ operations, as well as the risks and uncertainties set forth in Amylyx’ United States Securities and Exchange Commission (SEC) filings, including Amylyx’ Annual Report on Form 10-K for the year ended December 31, 2023, and subsequent filings with the SEC. All forward-looking statements contained in this press release and related comments in our earnings conference call speak only as of the date on which they were made. Amylyx undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made.
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FAQ
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