Itovebi Approved for Breast Cancer

On Oct. 10, 2024, Genentech announced that the U.S. Food and Drug Administration (FDA) approved Itovebi^™ (inavolisib). Itovebi is an oral PI3 kinase (PI3K) inhibitor for use in combination with Ibrance^® (palbociclib) and fulvestrant for the treatment of PIK3CA-mutated hormone receptor-positive (HR+), HER2-negative (HER2-) locally advanced or metastatic breast cancer (as detected by an FDA-approved test) following recurrence on or within 12 months of completing adjuvant endocrine treatment. The recommended dose for inavolisib is 9mg orally once a day.  Genentech plans to launch Itovebi in the coming weeks. For complete prescribing information, please look here.

At a Glance

• Brand Drug: Itovebi^™ (inavolisib)
• Manufacturer: Genentech
• Date Approved: Oct. 10, 2024
• Indication:  for use in combination with Ibrance^® (palbociclib) and fulvestrant for treatment of PIK3CA-mutated HR+/HER2- locally advanced or metastatic breast cancer (as detected by an FDA-approved test) following recurrence on or within 12 months of completing adjuvant endocrine treatment
• Dosage Forms Available: 3mg and 9mg tablets
• Launch Date: In the coming weeks
• Estimated Annual Cost: Pricing information is not yet available.
• Approximately 310,720 women will be diagnosed with breast cancer in 2024 in the United States. It is estimated that HR+/HER2- breast cancers account for 60-70% of all breast cancer cases. Of those 200,000 cases, about 40% are estimated to be PIK3-mutated.
• Phosphoinositide 3-kinases (PI3K) are a large group of related signaling enzymes. One of them, PI3KC, is associated with cancer. With four isoforms (functionally similar but slightly structurally different proteins), PI3KC promotes cell growth, mobility, progression and survival. The alpha (A or α) PI3KC mutation is the only isoform known to be associated with breast cancer.
• Itovebi blocks the PI3K protein allowing it to suppress tumor growth and has a high potency and specificity for the PI3K α isoform.  When used in combination with palbociclib and fulvestrant, it produces a stronger anti-cancer effect than with each treatment alone.
• In Phase III studies, the Itovebi-based regimen met the primary endpoint of progression-free survival and reduced the risk of worsening disease or death by 57% when compared to palbociclib and fulvestrant alone in the first-line setting (15 months vs 7.3 months; p<0.0001). Overall survival data is not yet available.
• Studies showed Itovebi was well tolerated with no severe adverse events (AE) observed. The majority of AEs were mild to moderate and included hyperglycemia, diarrhea, rash and stomatitis (mouth sores).
• Other PIK3 inhibitors indicated for HR+/HER2- advanced breast cancer with a PIK3CA mutation include Piqray^® (alpelisib – Novartis) and Truqap^® (capivasertib – AstraZeneca Pharmaceuticals).
• The FDA also approved Foundation Medicine’s FoundationOne^® Liquid CDx as a companion diagnostic to identify patients as an FDA approved pharmacogenetic test must be used to detect PIK3CA-mutated breast cancer.
• Itovebi is a breakthrough therapy that was approved more than a month ahead of its Nov. 27, 2024, FDA action date.