In early 2016, a DCI physician scientist who’d completed her doctoral training in McDonnell’s lab — Stephanie Gaillard, MD, PhD — came across an ESR1 mutation in an ovarian cancer. Gaillard shared this with the lab, believing McDonnell might have some ideas as to how to leverage this information to help patients whose cancers harbored these ESR1 mutations.
Kaitlyn Andreano, a graduate student in McDonnell’s lab, took on the project.
“Kaitlyn decided to collect or synthesize nearly every endocrine drug that had ever been made, which is easy enough to do in my lab because we've been involved in the development of most of them, and she screened and found that lasofoxifene alone was effective against pretty much all of the ESR1 mutations, it didn't seem to care,” said McDonnell. “We knew that if you developed an ESR1 mutation, you would be resistant to all the endocrine therapies we have, but lasofoxifene was different. That was the discovery. As it turned out, the story with mutations is a lot more complex than people make it out to be….”
Predicting that lasofoxifene would work in ER+ breast cancer, the lab filed what’s called “an invention disclosure” on May 25, 2016.
Next, Andreano pushed for a utility patent. Without this, she and McDonnell assessed, the “old drug” would never be developed. Because the discovery was made in a Duke lab, Duke University filed, in Oct. 2017,The patent was issued in April 2019 with Andreano, Ching-Yi Chang, PhD, MSPH, (research associate professor of Pharmacology and Cancer Biology and McDonnell Lab member), Gaillard, and McDonnell listed as inventors. Lasofoxifene looked promising — where other endocrine therapies had failed — for the treatment of metastatic breast cancer in patients with the ESR1 mutation. Next, to translate these findings in the lab to clinical use.
The owner of the U.S. rights to lasofoxifene at the time was Ohio-based Sermonix Pharmaceuticals.
The company’s CEO David Portman, MD, had acquired the rights to the drug in February 2015, just a couple months after he and his wife Miriam Davidson Portman, MD, founded the company.
Portman — an OB-GYN by training and clinical researcher in women’s health, sexual medicine and menopause — had been principal investigator for Pfizer during some of their phase two and phase three studies of lasofoxifene in osteoporosis and he’d also consulted on the drug’s gynecological effects, including the alleviation of vaginal dryness/atrophy in menopause that can cause painful intercourse and sexual dysfunction.
He knew that Pfizer had received European Union authorization in 2009 to market lasofoxifene as a treatment for osteoporosis in postmenopausal women, but chose not to market it after acquiring Wyeth and a competing drug — a similar SERM designed to treat osteoporosis called Conbriza (bazedoxifene). He was also aware that the three-year marketing authorization had lapsed in 2012 and the rights to lasofoxifene had reverted to Ligand.
“This particular compound was looking for a good home,” said Portman. “We were fully prepared to try to move it forward in what had already been studied in menopause and osteoporosis, to pick up where Pfizer left off, but we came across this data (from the invention disclosure filed by the McDonnell lab) about a year into our efforts and this seemed to be a much more important area of unmet medical need. We had no idea, when we started, that we’d end up in the metastatic breast cancer space.”
On Nov. 8, 2016, even before a patent was issued, Sermonix and Duke’s Office of Licensing and Ventures (Duke OLV) came to an agreement whereby the company would acquire exclusive rights to further develop what was Duke’s intellectual property, and, if FDA-approved, commercialize lasofoxifene to treat advanced and metastatic breast cancer. Bryan Baines, RPh, director of scientific collaboration with OLV, facilitated the contract.
Sermonix also expanded its agreement with Ligand from U.S. rights to worldwide licensing rights, clearing the way for a launch of an international multi-site clinical trial — Evaluating LAsofoxIfeNe in ESR1 Mutations trial, the ELAINE Study, named for Portman’s sister-in-law Elaine Davidson Nemzer, MD, a child psychiatrist who passed away from metastatic breast cancer 20 years previous at the age of 47.