SWITZERLAND – The U.S. Food and Drug Administration (FDA) has granted approval to Roche’s Itovebi (inavolisib) in combination with Pfizer’s Ibrance (palbociclib) and AstraZeneca’s Faslodex (fulvestrant) as a first-line therapy for select breast cancer patients.
This significant development marks a promising advancement in the treatment of hormone receptor-positive, HER2-negative breast cancer with specific genetic mutations.
Itovebi’s combination therapy is designed for patients with endocrine-resistant, PIK3CA-mutated, hormone receptor-positive, HER2-negative locally advanced or metastatic breast cancer.
This indication applies to patients who have experienced recurrence after completing adjuvant endocrine therapy, as determined by an FDA-approved diagnostic test.
Competitive landscape
The introduction of Itovebi presents a formidable challenge to Novartis’s Piqray (alpelisib), which previously held the market since its FDA approval in 2019.
Although Piqray enjoyed an early advantage, industry analysts from GlobalData forecast that Itovebi will surpass Piqray in sales, potentially generating over US $1 billion by 2030, compared to an estimated US $480 million for Piqray during the same period.
Clinical trial insights
The FDA’s approval is backed by promising results from the Phase III INAVO120 trial (NCT04191499), which assessed the efficacy of the Itovebi combination in 325 breast cancer patients.
According to Roche’s findings, patients receiving the Itovebi combination achieved a mean progression-free survival (PFS) of 15 months, significantly higher than the 7.3 months seen in the control group receiving placebo alongside Ibrance and Faslodex.
While overall survival data remain inconclusive at this stage, Roche noted a “clear positive trend” favoring the Itovebi combination. The trial also reported improvements in secondary endpoints, including objective response rates and duration of response.
Safety profile
Common Grade 3/4 adverse effects associated with the Itovebi regimen included hematological abnormalities such as neutropenia, thrombocytopenia, anemia, hyperglycemia, and stomatitis.
Notably, discontinuation rates were recorded at 6.8% for the Itovebi group compared to just 0.6% in the placebo cohort.
Roche is keen to expand Itovebi’s label and is currently evaluating its effectiveness in additional breast cancer indications.
The Phase III INAVO121 trial (NCT05646862) will compare Itovebi with Piqray in HR-positive/HER2-negative breast cancer patients who have previously received CDK4/6 inhibitor and endocrine combination therapy.
Another Phase III trial, INAVO122 (NCT05894239), aims to assess Itovebi in combination with Roche’s FDA-approved therapy Phesgo (pertuzumab, trastuzumab, and rHuPH20) for patients with previously untreated HER2-positive advanced breast cancer.
Roche’s strategic outlook
Roche’s ambition for Itovebi is underscored by the drug’s projected peak sales of 2 billion Swiss francs (US $2.3 billion).
Teresa Graham, Roche’s pharma chief, has voiced confidence in Itovebi’s potential to outpace competitors like Novartis’ Piqray and AstraZeneca’s AKT inhibitor Truqap, citing Itovebi’s superior efficacy and tolerability.
Roche’s move to strengthen its breast cancer portfolio follows other notable developments, such as the recent acquisition of early-stage CDK4/6 inhibitors from Regor Pharmaceuticals and the ongoing development of its oral SERD drug giredestrant for HR+/HER2- breast cancer.
