Gilead To Discontinue Phase 3 Study of Magrolimab Plus Azacitidine in Higher-Risk MDS

Rare Daily Staff

Gilead Sciences said that it is stopping the phase 3 ENHANCE study of magrolimab in higher-risk myelodysplastic syndromes due to futility based on a planned analysis.

Myelodysplastic syndromes (MDS) are a rare group of blood cancers characterized by abnormal development of blood cells within the bone marrow. Approximately 15,000 people are diagnosed with MDS in the United States each year, and the average survival rate for those with lower-risk MDS is six years and approximately 18 months for those with higher-risk MDS.

Individuals with MDS have abnormally low blood cell levels with symptoms including dizziness, fatigue, weakness, shortness of breath, bruising and bleeding, frequent infections, and headaches. In some cases, MDS may lead to bone marrow failure or an acute leukemia. The exact cause of MDS is unknown. It sometimes runs in families, but no disease-causing gene has been identified. Treatment depends on the affected individual’s age, general health, and type of MDS and may include red cell and/or platelet transfusions and antibiotics.

Magrolimab is a potential first-in-class, anti-CD47 immunotherapy that Gilead acquired when it paid $4.9 billion for the biotech Forty Seven three years ago. It has a clinical development program spanning ten potential indications including ongoing trials in solid tumors and two pivotal trials: ENHANCE-2 study in acute myeloid leukemia (AML) with TP53 mutations and ENHANCE-3 in first-line, unfit AML.

“The health and well-being of patients are our top priorities and while this is disappointing news it confirms the challenges of treating HR-MDS, where no new class of treatments have been approved in nearly 20 years,” said Merdad Parsey, chief medical officer, Gilead Sciences.

Gilead is working with study investigators on appropriate next steps for patients enrolled in the ENHANCE study. Data will be submitted for presentation at an upcoming medical meeting.

The Phase 3 randomized, double-blind study evaluated the combination of magrolimab plus azacitidine as first-line treatments for higher-risk myelodysplastic syndromes (HR-MDS), a disease without a new class of treatments approved in almost 20 years. The study enrolled more than 500 patients who were randomized to receive magrolimab in combination with azacitidine or azacitidine monotherapy. Primary endpoints were complete response and overall survival. Secondary endpoints included duration of response, transfusion independence, progression free survival, and time to transformation to acute myeloid leukemia, among others. The safety data seen in this study is consistent with the known magrolimab profile and adverse events that are typical in this patient population. Gilead recommends discontinuing treatment with magrolimab in patients with HR-MDS.

Photo: Merdad Parsey, chief medical officer, Gilead Sciences