In mysterious FDA approval, Pfizer quietly wins Ibrance breast cancer expansion

It’s unusual to have the FDA chase down a pharma company and ask them apply for a new drug indication. But Pfizer went through just that and has now quietly revealed a label expansion for blockbuster breast cancer med Ibrance.

The FDA has extended Ibrance’s approval in combination with an aromatase inhibitor to include newly diagnosed HR-positive, HER2-negative metastatic breast cancer patients regardless of menopausal status, Pfizer said Tuesday.

Previously, the combination of Ibrance and an aromatase inhibitor was limited to use in postmenopausal women. By Pfizer’s estimate, pre/perimenopausal women represent about 17% of the HR+/HER2- breast cancer patients.

The FDA granted the new approval in mid-December, according to an approval letter (PDF), but Pfizer snuck the news into its fourth-quarter earnings announcement Tuesday.

There are other unconventional elements in this approval beyond Pfizer’s late, low-profile revelation.

For one, a review of Ibrance’s updated prescription information (PDF) shows no new efficacy data in the patient population.

The clinical efficacy section of Ibrance’s label still only includes results from the phase 3 PALOMA-2 trial—which tested a combination of Ibrance and Novartis’ aromatase inhibitor Femara in postmenopausal women newly diagnosed with HR+/HER2- breast cancer—and from the phase 3 PALOMA-3 study. The latter study tested Ibrance with AstraZeneca's SERD drug Faslodex in previously treated patients regardless of menopausal status.

Ibrance’s expansion comes more than four years after Novartis’ Kisqali became the first CDK4/6 inhibitor approved for this patient population when used with an aromatase inhibitor as initial endocrine-based therapy. That Novartis nod made history back in July 2018 as the first granted under the FDA’s real-time oncology review framework, which allows for simultaneous data submission and FDA review.

At that time, Kisqali’s broad label was based on tumor progression data from the phase 3 MONALEESA-7 trial in pre- or perimenopausal women. The trial later showed Kisqali could significantly prolong patients’ lives, too, when compared with placebo in their respective combinations with an aromatase inhibitor.

While Novartis designed MONALEESA-7 to persuade the FDA, it was the FDA that proactively reached out to Pfizer in this case. In December 2021, the FDA requested that Pfizer file an application to include pre/perimenopausal women in Ibrance’s label, and Pfizer submitted its application on March 11, 2022, according to an FDA approval letter dated Dec. 13, 2022. Pfizer had been working to expand this indication before the FDA's request, a company spokesperson told Fierce Pharma.

The unusual approval raises a question around the basis of FDA’s decision to request—and then approve—the Ibrance expansion.

In a statement to Fierce Pharma, the agency pointed to its guidance published mid-2021 on developing drugs for premenopausal women with breast cancer. The agency noted that these young women have historically been excluded from clinical trials, and running new studies has led to delays in availability of treatment.

For drugs like Ibrance that target the hormonal axis, the “FDA believes these drugs when given to premenopausal women with adequate estrogen suppression are likely to have generally the same efficacy and safety profile as in postmenopausal women, based on a review of the nonclinical, clinical pharmacology, and clinical literature,” the FDA said.

Pfizer used some relevant subgroup analyses from PALOMA-2 and PALOMA-3 as well as an investigator-initiated phase 2 trial conducted in South Korea back in 2019 for this application, the Pfizer spokesperson told Fierce Pharma.

This isn’t the first time that Pfizer and the FDA went beyond regulatory norms to get Ibrance an approval. Back in 2019, the FDA used real-world evidence to grant Ibrance an approval for use alongside either an aromatase inhibitor or Faslodex in men with breast cancer.

The new approval comes as Ibrance is under increased pressure from Novartis’ Kisqali and Eli Lilly’s Verzenio, particularly after the final overall survival analysis of the PALOMA-2 trial found Ibrance didn’t significantly improve patients’ life expectancy.

For 2022, Ibrance sold $3.37 billion in the U.S., down 1% year over year. Pfizer has attributed the drug’s stagnant performance to more patients using the drug through an assistance program.

Editor's Corner: The story has been updated on Feb. 1 to include additional information from Pfizer, including the evidence the company used for its FDA application.