FDA Allows Magrolimab Studies to Continue in Patients With MDS and AML

Magrolimab clinical trials including patients with myelodysplastic syndrome and acute myeloid leukemia may continue now that the FDA has lifted a partial clinical hold.

The FDA has lifted the partial clinical hold placed on studies of magrolimab in combination with azacitidine (Vidaza). Comprehensive safety data were reviewed by the FDA from all studies, leading the regulatory body to their decision.1

Uncertain data around the investigator-reported serious adverse reaction between treatment arms was the reason for the partial clinical hold placed in January 2022. At the time, there was no clear adverse event (AE) profile for the combination and no new safety signal had been observed. The partial clinical hold temporarily stopped screening and enrollment of patients with myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML).

Enrollment in the studies can now resume for trials of magrolimab plus azacitidine in the United States. For international studies, the developer, Gilead Sciences, Inc, is working with regulatory agencies to reopen enrollment.

“Our confidence in the risk-benefit profile of magrolimab has been unwavering, and we continue to believe in the potential for this treatment to address the unmet medical needs faced by people living with MDS and AML,” said Merdad Parsey, MD, PhD, chief medical officer, Gilead Sciences, in a statement. “This is a significant milestone for Gilead and, more importantly, for patients diagnosed with these cancers. We look forward to continuing our work developing magrolimab and advancing this potential cancer treatment option.”

The lift of the partial clinical hold on magrolimab studies is good news for the phase 3 ENHANCE clinical trial (NCT04313881) of magrolimab plus azacitidine verse azacitidine plus placebo in untreated patients with MDS. The randomized, double-blind, multicenter study met the pre-specified enrollment threshold required for the first interim analysis prior to hold being placed.1,2

ENHANCE will include 520 patients with newly-diagnosed MDS who have adequate performance status and hematological, liver, and kidney function. Patients will be evaluated for the coprimary end points of complete remission (CR) rate and overall survival.2

The secondary end points of the study include duration of CR, objective response rate, duration of response, red blood cell transfusion independence rate, event-free survival, minimal residual disease negativity response rate, time to transformation to AML, percentage of patients with treatment-emergent AEs, serum concentration of magrolimab, anti-magrolimab antibody positivity occurrent rate, and quality of life determine by Functional Assessment of Cancer Therapy-Anemia response rate. A read out of data from ENHANCE is expected from the company in 2023.

The preliminary efficacy of magrolimab and azacitidine has already been demonstrated, based on results from the randomized, open-label ENHANCE-2 study (NCT04778397). In the study magrolimab/azacitidine was compared with azacitidine plus intensive chemotherapy in patients with TP53-mutant AML, including patients with MDS. Among the 24 patients with MDS in the study, the ORR observed with magrolimab/azacitidine administered at 75 mg/m2 was 92%, including a 50% CR rate, a 33% marrow CR rate, and an 8% hematologic improvement. Stable disease was also observed in 8% of patients.3

In the AML cohort (n = 22), magrolimab plus azacitidine achieved an ORR of 64%, which consisted of a 41% CR rate, CR with complete blood count recovery in 14% of patients, and morphologic-leukemia-free state in 5%. Thirty-two percent of patients in the cohort had SD while 5% had progressive disease.

The median overall survival was not reached in either cohort with a median follow-up of 6.4 months (range, 2.0-14.4) in the MDS cohort and 8.8 months (range, 1.9-16.9) in the AML cohort.

Both ENHANCE and ENHANCE-2 are ongoing studies will prospective completion dates of February 2025 and July 2025, respectively.2,4

Gilead is now shifting its focus to working with the FDA to remove the partial clinical on hold on trials of magrolimab in patients with diffuse large B-cell lymphoma. No studies of magrolimab in patients with solid tumor were affected by the partial clinical hold.1

REFERENCES:

1. FDA lifts partial clinical hold on MDS and AML magrolimab studies. News release. Gilead Sciences, Inc. April 11, 2022. Accessed April 12, 2022. https://bit.ly/3v8QIXb

2. Magrolimab + azacitidine versus azacitidine + placebo in untreated participants with myelodysplastic syndrome (MDS) (ENHANCE). Clinicaltrials.gov. Updated February 2, 2022. Accessed April 12, 2022. https://bit.ly/37CCwNY

3. Forty Seven, Inc. announces updated data from ongoing clinical trial of magrolimab showing robust, durable activity in patients with myelodysplastic syndrome and acute myeloid leukemia. News release. December 9, 2019. Accessed April 12, 2022. https://bit.ly/3fWKJxk

4. Study to Evaluate the safety and efficacy of magrolimab in combination with azacitidine versus physician's choice of venetoclax in combination with azacitidine or intensive chemotherapy in previously untreated adults with tp53 mutant acute myeloid leukemia (ENHANCE-2). Clinicaltrials.gov. Updated February 7, 2022. Accessed April 12, 2022. https://bit.ly/3o357Bv