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Novartis, determined to dethrone Pfizer, will launch bold Kisqali-Ibrance head-to-head trial in breast cancer

Despite two life extension wins, Novartis still finds it tough to convince doctors to use its breast cancer drug Kisqali over Pfizer’s first-to-market Ibrance. Now, with a third survival victory under its belt, the Swiss pharma is determined to overthrow its rival—and it’s launching an ambitious head-to-head trial to make it happen.

Sunday, Novartis said it’s collaborating with SOLTI Innovative Cancer Research to launch a new phase 3 trial for Kisqali and Ibrance. Dubbed Harmonia, the trial will pit the two CDK4/6 inhibitors—both used on top of endocrine therapy—against each other in patients with the HER2-enriched subtype of HR-positive, HER2-negative advanced breast cancer.

The news comes as Novartis churned out a third clinical trial success for Kisqali at the ongoing European Society for Medical Oncology annual meeting, whereas Ibrance’s clinical programs have yet to report a life-saving benefit for the Pfizer med. And it comes as Ibrance’s U.S. new-to-brand prescription numbers stay about 10 times that of Kisqali’s, despite its lagging behind in clinical data.

“The strength and consistency of the Kisqali overall survival data across the Monaleesa program reinforce there are differences among CDK4/6 inhibitors, and that Kisqali stands apart in its ability to help patients achieve their goal of more quality time,” Susanne Schaffert, Ph.D., president of Novartis Oncology, said in a statement Sunday.

“Harmonia, a novel head-to-head trial, is a testament to our bold development approach and will provide evidence on the unique profile of Kisqali and its unmatched benefit for HR+/HER2- advanced breast cancer patients,” Schaffert added.

With help from Alliance Foundation Trials, the new study will start enrolling patients in the first quarter of 2022 across 80 hospitals in Spain, Portugal and the U.S. The main goal is to see which therapy is better at delaying tumor progression or death. It will also assess whether Kisqali alters tumor biology in a way that enables better response to endocrine therapy compared to Ibrance, according to Novartis.

An exploratory cohort of the study will also enroll patients with a basal-like subtype of tumors, which resemble triple-negative breast cancer. These participants will get chemotherapy alongside the CDK4/6 inhibitors.

Novartis in 2019 unveiled two positive datasets from the Monaleesa-7 and Monaleesa-3 trials, detailing significant overall survival improvements for different Kisqali combos in premenopausal and postmenopausal women, respectively.

In contrast, Ibrance’s pairing with AstraZeneca’s Faslodex didn’t significantly outperform solo Faslodex at extending the lives of previously treated patients in the Paloma-3 trial. A smaller phase 2 trial dubbed Paloma-1 also failed to show a significant survival advantage for Ibrance’s use on top of Novartis’ aromatase inhibitor Femara. And the Pfizer drug also fell short as a postsurgical treatment in two trials in the adjuvant setting.

Still, Ibrance holds a seemingly unshakeable lead in market share. In the second quarter, Ibrance’s U.S. sales came in at $862 million, and its share in first-line new patient starts was strong at 73%, according to Pfizer. Kisqali brought in only $83 million in the same period.

According to SVB Leerink’s most recent tally of IQVIA data as of Sept. 10, Ibrance’s average new-to-brand scripts have been roughly stable at around 1,100 to 1,200 per week, while Kisqali’s were about 110. Eli Lilly’s Verzenio, probably thanks to its recent first-in-class adjuvant win, is seeing a growing number of new scripts, reaching 359 for an average of the last four weeks.

At ESMO 2021, Novartis unveiled new data from the Monaleesa-2 trial. It showed that adding Kisqali to Femara extended patients’ lives by one year, and the reduction in death risk reached 24%. Ibrance’s counterpart phase 3 trial, Paloma-2, has yet to report final overall survival data.

Gabriel Hortobagyi, M.D. of the MD Anderson Cancer Center, lead investigator of the Monaleesa-2 trial, has suggested that it may take a readout from the Paloma-2 trial to finally change doctors’ prescribing habits.

“If that [Paloma-2] trial is similarly positive to Monaleesa-2, then I think physicians will continue to prefer [Ibrance] simply because that’s their habit,” Hortobagyi said in an interview about Kisqali’s new data at ESMO 2021. “If that trial is negative, then I think … there will be an exodus from [Ibrance] to [Kisqali].”