Seventy percent of the 240,000 U.S. women diagnosed with breast cancer are ER+ positive. In the U.S. alone, there are an estimated 3 million breast cancer survivors as well as 160,000 women living with stage IV metastatic disease. The market is predicted to grow to 12 billion dollars by 2022. Most women with hormone positive breast cancer receive adjuvant endocrine therapy and eventually a large proportion become resistant through acquired resistance and mutations of the estrogen receptor. Lasofoxifene, a potent SERM with binding affinity and activity in mutations of the estrogen receptor, may hold promise for many patients in this area of unmet medical need. Novel IP around lasofoxifene’s efficacy signal in endocrine resistant breast cancer has recently been discovered and Sermonix has exclusive rights to patents around the identified signal. Lasofoxifene could play a vital role in the personalized treatment of advanced breast cancer, including potential companion diagnostics and be the ideal anti-estrogen to pair with newer agents—and those in development—for the treatment of advanced breast cancer.
Lasofoxifene, a third-generation selective estrogen receptor modulator (SERM), is one of the most well studied drugs in its category. It has been evaluated in more than 15,000 women in a comprehensive worldwide phase I-III clinical development program that includes the PEARL, OPAL and other trials, showing a positive impact on vulvovaginal atrophy (VVA), improvement in bone mass and a reduction in vertebral and non-vertebral fractures. The CORAL study—a randomized, blinded comparison of raloxifene and lasofoxifene—demonstrated greater bone density gains and higher response rates in the lasoxifene group. A recent exploratory analysis of CORAL also identified improved sexual activity and function in lasofoxifene-treated women.
The large PEARL clinical trial (>8500 postmenopausal women enrolled in a 5 year study) demonstrated that in women with osteoporosis, lasofoxifene significantly reduced the risk of vertebral fractures by 42 percent and non-vertebral fractures by 24 percent compared to placebo, and importantly, reduced estrogen-receptor positive breast cancer by 80 percent. Sermonix plans to seek FDA approval for the use of lasofoxifene to treat several women’s health indications, including breast and ovarian cancer treatment, and the management and treatment of osteoporosis and symptoms of VVA in breast cancer survivors and others.
While there are current therapies available that address some needs of the advanced breast cancer patient and survivor, not everyone benefits from such options. The SERD fulvestrant has poor bioavailability and newer drugs in development have tolerability issues. The development of resistance to aromatase inhibitors is a major concern. Joint aches and vaginal and sexual complaints lead to significant discontinuation rates on aromatase inhibitors as well. Chemotherapy has toxicities and patients are poorly compliant on bone-active agents like bisphosphonates. Consequently there is a significant unmet need for options and alternative in this space. Lasofoxifene, a potent, well-tolerated and bioavailable oral SERM could prove useful in improving breast cancer patients’ health in several common and important domains. Lasofoxifene has a large development program behind it and no other breast cancer medication confers such unique benefits that could potentially treat resistant breast cancer and extend and improve quality of life.