FDA Approves 2 Drugs for Acute Myeloid Leukemia (AML)

The US Food and Drug Administration (FDA) has approved 2 new drugs, Daurismo (glasdegib) and Venclexta (venetoclax), to treat people newly diagnosed with acute myeloid leukemia (AML) who are not candidates for intensive chemotherapy. This may be because they are 75 years old or older, or because they have a health condition that rules out standard treatment.

AML is typically treated with intensive courses of chemotherapy whenever possible, as this offers the best chance for a cure. But this treatment can cause serious side effects, and in some cases it might even do more harm than good. This is especially true in older patients or those with other serious health problems that might affect their ability to tolerate more intensive treatment. These drug approvals may offer new treatment options for these patients.

Daurismo (glasdegib)

Daurismo is a tablet that is to be used in combination with low-dose cytarabine, a type of chemotherapy. Daurismo is a type of targeted drug called a hedgehog inhibitor. It works by interfering with the hedgehog signaling pathway, which can cause out-of-control cell growth that can lead to some types of cancers.

The FDA based its approval of Daurismo on a randomized clinical trial of 111 people newly diagnosed with AML. Participants received either Daurismo along with low-dose cytarabine, or low-dose cytarabine alone. The trial measured overall survival, which is how long patients lived from the beginning of their treatment until their death. Those who received the drug combination had an average overall survival of 8.3 months compared to 4.3 months for those who received low-dose cytarabine alone.

Daurismo was approved using priority review, a process designed to speed up the availability of drugs to treat serious diseases. It was also granted orphan drug designation, which provides financial incentives to encourage the development of drugs for rare diseases.

Common side effects included low blood or platelet counts, fatigue, bleeding, fever, muscle pain, nausea, low appetite, swelling in the arms or legs, shortness of breath, taste changes, pain or sores in the mouth or throat, constipation, and rash.

A warning that comes with Daurismo states it should not be used during pregnancy or while breastfeeding. Women should not become pregnant while taking Daurismo and men should not father a child while taking Daurismo or for at least 30 days after the last dose. Patients should not donate blood or blood products during treatment. Their health care provider should monitor them for changes in the electrical activity of the heart.

Daurismo is marketed by Pfizer.

Venclexta (venetoclax)

Venclexta targets BCL-2, a protein in some cancer cells that helps them survive longer than they should. It’s taken as a pill once a day.

Venclexta is already on the market to treat people with chronic lymphocytic leukemia (CLL). The FDA based the new approval on 2 open-label, non-randomized clinical trials of people newly diagnosed with AML who could not take intensive chemotherapy. All the participants received Venclexta, and they all knew they were taking it. The trials measured the portion of patients going into complete remission, which means the leukemia could no longer be detected in the body, and they measured how long the complete remission lasted.

In one study, patients received Venclexta along with a chemotherapy drug, either azacitidine or decitabine. Of the 67 people who received Venclexta and azacitidine, 25 achieved complete remission, which lasted for an average of 5.5 months. Of the 13 people who received Venclexta and decitabine, 7 achieved complete remission, which lasted for an average of 4.7 months.

In the other study, 61 patients received Venclexta along with low-dose cytarabine. Complete remission was achieved by 13 patients for an average duration of 6 months.

Venclexta was approved using several FDA approaches designed to speed up the availability of drugs to treat serious diseases – breakthrough therapy designation, priority review status, and accelerated approval. It was also granted orphan drug designation, which provides financial incentives to encourage the development of drugs for rare diseases.

The most common side effects included nausea, vomiting, diarrhea, constipation, low blood and platelet counts, fever, infection, fatigue, swelling in the arms and legs, pneumonia, shortness of breath, bleeding, rash, pain, dizziness, cough, and low blood pressure.

Venclexta is manufactured by AbbVie Inc., and marketed by AbbVie and Genentech USA Inc.