Sermonix Pharmaceuticals Announces Publication of ELAINE-1 & ELAINE-2 Trial Results

Sermonix Pharmaceuticals Inc. recently announced results of its two Phase 2 Evaluation of Lasofoxifene in ESR1 Mutations (ELAINE) studies were published in Annals of Oncology, the peer-reviewed journal of the European Society for Medical Oncology (ESMO) and the Japanese Society of Medical Oncology.

The articles, published online and with open access in the December edition of the journal, are as follows:

• Lasofoxifene versus fulvestrant for ER+/HER2- advanced breast cancer with an ESR1 mutation: Results from the randomized, phase 2 ELAINE 1 trial
• Open-label, phase 2, multicenter study of lasofoxifene plus abemaciclib for treating women with metastatic ER+/HER2- breast cancer and an ESR1 mutation after progression on prior therapies: ELAINE 2

“These Phase 2 ELAINE studies ideally position Sermonix for the initiated global registrational ELAINE-3, Phase 3 study comparing lasofoxifene in combination with abemaciclib versus fulvestrant plus abemaciclib,” said Dr. David Portman, Sermonix Founder and Chief Executive Officer. “We are excited to share the results of our recent studies in this prestigious journal and to continue our path toward potential approval and commercial development of our novel targeted endocrine therapy.”

Top-line data for ELAINE-1, a study of postmenopausal women with locally advanced or metastatic estrogen receptor-positive (ER+)/HER2- breast cancer with an ESR1 mutation, were shared as an oral presentation at the 2022 ESMO Congress. The study demonstrated that lasofoxifene, a novel targeted and tissue-selective oral endocrine therapy that acts as an ER antagonist at the breast, numerically prolonged median progression-free survival (PFS) compared with fulvestrant (5.6 months vs. 3.7 months; P=0.138) in metastatic breast cancer patients with ESR1 mutations who had progressed taking a prior aromatase inhibitor (AI) and CDK4/6i, with a favorable safety profile. Also, 30.7% of patients on lasofoxifene achieved a PFS of 12 months compared to 14.1% on fulvestrant.

ELAINE-1 also demonstrated an objective response rate (ORR) of 13.3% for lasofoxifene compared to 2.9% for fulvestrant (P=0.124), and saw on lasofoxifene the first-ever known finding of a durable complete response – ongoing at 2.5 years – that could be characterized as complete clinical remission in a metastatic ER+/HER2- breast cancer patient with an ESR1 mutation after prior CDK4/6 inhibitor treatment and subsequent treatment with a single-agent hormonal therapy.

An exploratory ELAINE-1 analysis, shared in March 2023 at the International Society for the Study of Women’s Sexual Health (ISSWSH) Annual Meeting, found in patients presenting at baseline with moderate to severe vaginal and vulvar dryness/pain on a validated measurement scale that lasofoxifene numerically improved these symptoms compared to fulvestrant.

ELAINE-2 (NCT04432454), an open-label study of lasofoxifene in combination with Eli Lilly and Company’s CDK4/6 inhibitor abemaciclib, evaluated 29 heavily pre-treated women with ER+/HER2- locally advanced or metastatic breast cancer and an ESR1 mutation. Results were initially shared at a poster discussion session during the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting and updated in June at ASCO 2023.

The primary endpoint for ELAINE-2 was safety/tolerability, with secondary endpoints including PFS and ORR. With patient follow-up through Jan. 31, 2023, the combination of lasofoxifene and abemaciclib continued to be well-tolerated, with clinically meaningful efficacy in women with ER+/HER2- metastatic breast cancer and an ESR1 mutation. The PFS, a median of 13 months, and ORR of 56% were promising.

“Lasofoxifene has demonstrated compelling anti-tumor activity against tumors with increasingly prevalent ESR1 mutations, and potential benefit on quality of life with respect to vaginal and sexual health,” said Paul Plourde, MD, Vice President of Oncology Clinical Development for Sermonix. “We look forward to the results of ELAINE-3, and a greater understanding of lasofoxifene’s potential.”

An accompanying invited (closed-access) editorial by Dr. Seth Wander of Massachusetts General Hospital addresses the context of these two seminal trials in the current and future treatment landscape of ER+/HER2- advanced breast cancer.

Lasofoxifene is an investigational novel endocrine therapy in clinical development which has demonstrated robust target engagement as an ESR1 antagonist in the breast, particularly in the presence of ESR1 mutations. Lasofoxifene has demonstrated anti-tumor activity as monotherapy and in combination with a CDK4/6 inhibitor in Phase 2 studies and has unique tissue selectivity distinguishing it from other current and investigational endocrine therapies, with beneficial effects seen on vagina and bone in previous clinical studies. Lasofoxifene, which Sermonix licensed globally from Ligand Pharmaceuticals Inc. (NASDAQ:LGND), has been studied in previous comprehensive Phase 1-3 non-oncology clinical trials in more than 15,000 postmenopausal women worldwide. Lasofoxifene’s bioavailability and activity in mutations of the estrogen receptor could potentially hold promise for patients who have acquired endocrine resistance due to ESR1 mutations, a common finding in the metastatic setting and an area of high unmet medical need. Lasofoxifene’s novel activity in ESR1 mutations was discovered at Duke University and Sermonix has exclusive rights to develop and commercialize the product in this area. Lasofoxifene, a novel targeted and tissue selective oral endocrine therapy could, if approved, play a critical role in the precision medicine treatment of advanced ER+ breast cancer.

Sermonix Pharmaceuticals Inc. is a privately held biopharmaceutical company focused on the development of female-specific oncology products and is currently undertaking two Phase 2 clinical studies of lasofoxifene, its lead investigational drug. For more information, visit SermonixPharma.com.