Eli Lilly’s Verzenio has been chasing Pfizer's Ibrance in the metastatic setting since it hit the market. But with a “surprise” new win in early breast cancer, it finally has a chance to get ahead in a field where Ibrance just took a big blow.
Adding Verzenio to standard postsurgery endocrine therapy significantly cut the risk of cancer recurrence in patients with high-risk HR-positive, HER2-negative early breast cancer, Lilly said Tuesday.
The win, which Evercore ISI analyst Umer Raffat called a “surprise” in a Tuesday note, marks the first for a CDK4/6 inhibitor in the so-called adjuvant setting, in which the intention with treatment is to prevent invasive disease from returning. The sign of success, from a pre-planned interim analysis, comes nearly a year ahead of expectations and puts Lilly in line for a nod for what Raffat called a $3 billion to $4 billion indication.
Approximately 30% of people diagnosed with HR-positive, HER2-negative early breast cancer are at risk of their disease returning, according to Lilly. But the risk varies based on certain clinical or pathological features, such as whether the cancer has spread to the lymph nodes, the tumor size, and the tumor grade.
Lilly’s win also puts pressure on its in-class competitors, Ibrance and Novartis’ Kisqali. Pfizer recently said a planned interim analysis of the phase 3 Pallas trial found the Ibrance-endocrine therapy combo couldn’t top endocrine therapy alone at prolonging the time to tumor recurrence in HR-positive, HER2-negative early breast cancer.
News of that trial failure, which SVB Leerink analyst Geoffrey Porges suggested implied a peak Ibrance sales decrease of about $3.5 billion, slashed 7% off Pfizer’s stock.
So how did Lilly succeed where Pfizer failed? The Ibrance Pallas trial was different from Verzenio’s study, called monarchE, in that the Pfizer phase 3 included those at moderate to high risk of recurrence, while Lilly is carrying its trial out in a smaller group consisting of only high-risk early breast cancer patients.
During a conference call with investors in late January, Lilly Oncology chief Anne White said the company specifically designed the monarchE study in the high-risk population because it’s “where we believe that Verzenio would really differentiate.” The move also drove the speed of the trial, helping it read out results just a couple weeks after Pfizer's did.
Lilly previously indicated that a successful monarchE readout could increase Verzenio’s addressable patient population by around 50%, Cantor Fitzgerald analyst Louise Chen wrote in a Tuesday note to clients. “If the positive adjuvant data also shifts physicians' preferences to Verzenio as the preferred CDK4/6 inhibitor, we think the peak sales potential for Verzenio could reach $7.5B+,” compared with the current consensus of about $2.5 billion in 2025, she said.
But that’s a big if. Currently, Ibrance—helped by a two-year head start on the market—is the clear leader in the CDK pack, with 2019 sales of $4.96 billion. Verzenio raked in $580 million last year, and Kisqali came in third with a $480 million haul.
"Could this increase % share in metastatic? I doubt it," Raffat wrote.
But Porges figures Verzenio has a chance, especially since Ibrance previously also failed to show an overall survival benefit in the metastatic setting. In fact, he suspects Verzenio’s likely early adoption in the adjuvant setting could even lead to declining Ibrance sales after 2021, as patients will probably not get two CDK4/6 inhibitors without data supporting retreatment.
Pfizer's own hopes aren't completely lost in the adjuvant setting, though; it's also running the phase 3 Penelope-B study, testing Ibrance in patients with a high risk of recurrence following pre-surgery chemo. It’s slated to report interim results later this year. But as Porges noted, the study is examining a “very small subpopulation” within the adjuvant group.
Separately, Novartis is running a phase 3 trial called Natalee that’s testing its CDK4/6 inhibitor Kisqali on top of endocrine therapy in the adjuvant treatment of HR-positive, HER2-negative early breast cancer, and it's hoping to see results by 2022. But in his note, Raffat said the Novartis trial with 4,000 patients may be “underpowered” to show a clear benefit. In contrast, Pallas enrolled 4,600 patients and monarchE has 5,637.
In the U.S., Verzenio is currently allowed, when paired with an aromatase inhibitor, to treat postmenopausal women as an initial therapy for HR-positive HER2-negative breast cancer. It can also be given alongside fulvestrant to treat cancer that has progressed on endocrine therapy, or on its own in those with metastatic disease previously treated with endocrine therapy and chemotherapy.
As Lilly expects to submit the interim results to regulatory authorities, it will continue the monarchE study for final survival analysis, which is expected in 2027.