Sermonix’s Lasofoxifene Improves Vaginal/Vulvar Symptoms Relative to Fulvestrant in ELAINE 1 Study of Postmenopausal Women With Locally Advanced or Metastatic ER+/HER2- Breast Cancer and an ESR1 Mutation

Sermonix Pharmaceuticals Inc. recently announced that its lead drug candidate, lasofoxifene, improved vaginal/vulvar symptoms while fulvestrant worsened them in a study of postmenopausal women with locally advanced or metastatic estrogen receptor-positive (ER+)/HER2- breast cancer with an ESR1 mutation.

The results, derived from the open-label randomized Evaluation of Lasofoxifene in ESR1 Mutations (ELAINE 1, NCT03781063) study, were shared March 4 in an e-poster presentation at the International Society for the Study of Women’s Sexual Health (ISSWSH) Annual Meeting 2023 in St. Louis.

Top-line data for ELAINE 1, which began enrollment in September 2019, were shared in September at the European Society for Medical Oncology (ESMO) Congress 2022. This secondary analysis aimed to investigate changes in vaginal/vulvar symptoms with lasofoxifene versus fulvestrant, as lasofoxifene improved symptoms of vulvovaginal atrophy (VVA) in two previous Phase 3 studies among postmenopausal women with moderate to severe VVA.

Vaginal/vulvar symptoms were evaluated in an exploratory analysis using the vaginal (VAS) and vulvar (VuAS) assessment scales, instruments validated in breast cancer patients to assess dryness, soreness, irritation, and pain.

• Among patients who completed the VAS/VuAS at baseline, the mean composite VAS/VuAS score decreased (improved) from baseline to week 16 by 74% in lasofoxifene patients, but increased (worsened) by 36% in fulvestrant patients
• In the subgroup of patients with ≥1 moderate/severe symptom(s) at baseline, mean composite VAS/VuAS score decreased from baseline to week 16 by 72% with lasofoxifene, in contrast to an increase of 32% with fulvestrant
• The mean score for the most bothersome symptom decreased from baseline to week 16 by 65% with lasofoxifene versus 5% with fulvestrant
• Of 103 enrolled patients, 75% of lasofoxifene patients and 65% of fulvestrant patients completed the VAS/VuAS at baseline; among them, 23% and 30% had ≥1 moderate/severe symptom(s), respectively
• Women who completed the VAS/VuAS at baseline had a median age of 61.5 years

“This small-sample-sized exploratory analysis shows that lasofoxifene at 5 mg/day may potentially provide clinical benefits on vaginal and sexual health when treating metastatic breast cancer, though further studies are warranted to confirm such beneficial effects,” said Shari B. Goldfarb, M.D., assistant attending physician, Memorial Sloan Kettering Cancer Center.

ELAINE 1 demonstrated that lasofoxifene, a novel targeted and tissue-selective oral endocrine therapy that acts as an ER antagonist at the breast, preliminarily prolonged median progression-free survival compared with fulvestrant (6.04 vs 4.04 months; P=0.138) in metastatic breast cancer patients with ESR1 mutations who had progressed taking a prior aromatase inhibitor (AI) and cyclin-dependent kinase 4 and 6 inhibitor (CDK4/6i), with a favorable safety profile.

Novel therapies with positive impacts on vaginal health are desirable for breast cancer patients as estrogen-depleting AIs and degraders, and modulators of the estrogen receptor are associated with symptoms of genitourinary syndrome of menopause.

“Sermonix is pleased with the results of this study, which when combined with the primary ELAINE 1 findings as well as lasofoxifene’s well-researched history of improving vulvovaginal atrophy in postmenopausal women, demonstrate its potential as a novel therapy that clearly fills an unmet medical need,” said Dr. David Portman, Sermonix Founder and Chief Executive Officer. “We look forward to further investigating lasofoxifene’s efficacy, as a treatment for metastatic breast cancer with fewer negative side effects that greatly impact patients’ quality of life.”

Lasofoxifene is a novel targeted and tissue-selective oral endocrine therapy in clinical development that has demonstrated robust target engagement as an ESR1 antagonist in the breast, particularly in the presence of ESR1 mutations. Lasofoxifene demonstrated anti-tumor activity as a monotherapy and in combination with abemaciclib in Phase 2 studies and has unique tissue selectivity, distinguishing it from other current and investigational endocrine therapies. It also demonstrated beneficial effects on bone, lipids, and vaginal and sexual health 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. Its 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 could, if approved, play a critical role in the precision medicine treatment of advanced HR+ breast cancer.

Sermonix Pharmaceuticals Inc. is a privately held biopharmaceutical company focused on the development of female-specific and patient-centric oncology products and has currently completed two Phase 2 clinical studies of lasofoxifene, its lead investigational drug. The Sermonix management team, led by founder Dr. David Portman, has significant experience in all stages of the drug development, regulatory and commercialization processes. Paul Plourde, MD, Vice President of Oncology Clinical Development, has many decades of experience at AstraZeneca in the breast cancer drug development arena. Barry Komm, PhD, Chief Scientific Officer, is recognized for his expertise in nuclear receptor biology. Miriam Portman, MD, is Co-founder and Chief Operating Officer, with expertise in clinical trial conduct and patient recruitment. Elizabeth Attias, MMSc, ScD, Chief Strategy and Development Officer, has extensive experience in pharmaceutical drug commercialization. Simon Jenkins, PhD, Vice President of Operations, has over 30 years of experience in global drug development leadership. Sermonix non-executive chairman of the board is Anthony Wild, PhD, former President of both Parke-Davis Pharmaceuticals and Warner-Lambert’s Pharmaceutical Division. For more information, visit SermonixPharma.com.