Genentech’s new breast cancer drug Inavolisib, approved in the United States on October 15, 2024, works by doing two things at once to a mutated enzyme inside cancer cells: it blocks the enzyme’s activity and then it degrades the enzyme itself. That dual action is the core of the drug’s design.
Inavolisib, sold under the brand name Itovebi, targets a specific mutated form of an enzyme called phosphatidylinositol 3-kinase alpha, or PI3K alpha. The gene that codes for this enzyme is called PIK3CA. When that gene is mutated, the enzyme can become stuck in the “on” position, driving cancer cells to grow and survive in ways normal cells do not. Inavolisib is built to shut that process down.
The drug is classified as both an inhibitor and a degrader. An inhibitor simply blocks the enzyme’s activity. A degrader goes further, marking the mutated protein for destruction inside the cell. This means the drug not only stops the enzyme from working at that moment, but it also reduces the total amount of the faulty enzyme present. The thinking is that this could make it harder for cancer cells to adapt and find a way around the drug.
The approval came after clinical trials that tested the drug’s safety and effectiveness. The report does not give specific numbers from those trials, but the fact that the U.S. regulatory system cleared Inavolisib means the evidence met the required standards. For patients with breast cancer driven by PIK3CA mutations, this offers a treatment option that targets the molecular cause of their disease rather than attacking all rapidly dividing cells.
Breast cancer is not one disease. It is a collection of subtypes defined by which receptors or mutations are present. PIK3CA is one of the most commonly mutated genes in breast cancer. A drug that hits that mutation directly is a more precise tool than older chemotherapies. Itovebi is not a broad poison. It is aimed at a specific vulnerability.
The drug is not without risks. The most common side effects reported include gastrointestinal disorders, high blood glucose, and infections. These are not minor issues. High blood glucose, in particular, is a known problem with drugs that inhibit PI3K, because that enzyme is involved in insulin signaling. Patients on Inavolisib will need monitoring for these effects. Doctors will have to balance the drug’s potential to control the cancer against the burden of managing its side effects.
Genentech, which is part of the Roche group, developed Inavolisib. The company now faces the work of getting the drug into clinics and into patients who can benefit. That means identifying which patients carry the PIK3CA mutation through genetic testing of their tumors. It also means training oncologists on how to manage the side effect profile.
The October 15 approval date now marks a clear before and after for patients with this mutation. Before that date, no drug in the U.S. was specifically approved to both inhibit and degrade mutated PI3K alpha. After that date, there is one. Whether Inavolisib proves to be a meaningful advance over existing PI3K inhibitors will depend on real-world use and longer follow-up. But the mechanism itself is distinct. A drug that degrades its target rather than just blocking it is a different kind of tool in oncology.
