MADRID— If Eli Lilly could simply offer up an oral option in place of Faslodex for patients with breast cancer, Jacob Van Naarden would be pretty happy.
Early evidence shows that the Indianapolis-based pharma’s selective estrogen receptor degrader (SERD) imlunestrant may be able to do that, with a safety profile suggesting improved combinability with standard of care in the disease.
Lilly revealed early safety, pharmacokinetics and preliminary efficacy data from the phase 1a/b EMBER study Sunday at the European Society for Medical Oncology (ESMO) Congress in Madrid. Patients in the study have ER+, HER2-advanced breast cancer and received imlunestrant alone or with Lilly’s Verzenio or Novartis’ Piqray.
Van Naarden, who serves as president of Loxo@Lilly, said the goal of the trial is to show how imlunestrant combines with other medicines. Lilly’s ultimate hope for the oral SERD is to create a new “backbone” therapy in this type of breast cancer, but the company has much to prove before this can become a reality.
“Part of making doctors comfortable with that is showing that the drug can be safely combined with other agents that they use,” Van Naarden said, adding that this portion of the EMBER program is a “safety experiment.”
Lilly saw no added toxicity with imlunestrant in the early data and no drug-drug interactions.
But Lilly will have a lot to prove in the SERD class itself. The current standard of care for this population is AstraZeneca’s Faslodex, or fulvestrant, which must be administered as an intramuscular injection in a doctor’s office, according to Van Naarden. The SERD injection is painful to receive and is a burden on patients who have to go out of their way to get it. Treatment can be inaccessible to those who live in rural areas or have challenges accessing healthcare via insurance, Van Naarden said.
So pharmas like Lilly have been pushing—with limited success—to create oral versions.
“If that’s what these medicines end up being, that alone I actually think is a meaningful advance for the field,” Van Naarden said in an interview on the sidelines of the ESMO congress. “I know we’re used to thinking about superior efficacy all the time in oncology and by the way—it’s possible these medicines deliver that, which would be great—but actually even equivalent efficacy to fulvestrant is a meaningful advance for patients, just given the way in which fulvestrant has to be delivered to patients, is just so patient-unfriendly.”
Last year, Sanofi abandoned an oral SERD candidate after it failed in phase 3. Van Naarden said that, of course, Lilly has watched its peers and tried to learn as much as possible to ensure success in the imlunestrant program.
While better administration may have sparked the search, Van Naarden says there’s another reason Lilly is interested: SERD medicines can overcome resistance to aromatase inhibitors that are used in estrogen receptor-positive breast cancer. Lilly hopes to develop a new so-called “backbone” therapy to this regimen that can be part of the standard combination.
Lilly is working on a trio of studies for imlunestrant, including the three-arm EMBER-3 in second line ER+ breast cancer. The therapy will be tested alone, against Faslodex and in combination with Lilly’s Verzenio, also known as abemaciclib. That registrational study is due to read out in the first half of next year, and Van Naarden expects to be able to use it to support a filing for approval.
EMBER-4, meanwhile, is an adjuvant study testing imlunestrant against high-risk disease, where patients typically undergo endocrine therapy for five to 10 years after surgery.The study will allow patients to switch to imlunestrant midway through to measure the long-term outcomes and disease recurrence.
“There’s long been this lore among breast cancer oncologists that early into the adjuvant journey, they sort of have a sense sometimes for patients who maybe aren’t doing well on the endocrine backbone that they have,” Van Naarden said.
The trial was designed specifically to test the theory. It will enroll 6,000 patients—the largest study ever run by Lilly, according to Van Naarden.
“There’s a lot of patients who have this setting of disease, [it could be a] big impact kind of medicine, if the study ends up working, but we’ve got some time before we’re going to know,” Van Naarden said.
ESMO got a peek at what could be to come for imlunestrant, but efficacy data will have to wait.
“In some ways, we’re trying to sort of rule out negatives and I think we checked both those boxes,” Van Naarden said of the initial EMBER data. “So while we measured efficacy, and efficacy looks nice, I don’t think you can make any comparative statements about that.”