December 6, 2023

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Gilead: CD47 Antibody Development Hit by Second Phase III Trials Termination

Gilead: CD47 Antibody Development Hit by Second Phase III Trials Termination



Gilead: CD47 Antibody Development Hit by Second Phase III Trials Termination.

On September 27th, Gilead announced the termination of the Phase III clinical trial ENHANCE-2 for the CD47 antibody Magrolimab in the treatment of acute myeloid leukemia (AML) patients carrying TP53 mutations. This marks the second Phase III trial of this drug to be terminated by Gilead, following the discontinuation of the ENHANCE study for high-risk myelodysplastic syndromes (MDS) back in July.

According to Gilead, an interim independent analysis of the ENHANCE-2 study indicated that the treatment was “unlikely to demonstrate a survival benefit” compared to standard therapy, leading to the decision to terminate it. In fact, Gilead had initiated three Phase III clinical trials for Magrolimab, with ENHANCE and ENHANCE-2 now both discontinued, leaving only the ENHANCE-3 study for AML patients unfit for intensive chemotherapy as the remaining frontline treatment.

It’s worth noting that in August of this year, Gilead’s research on the CD47 antibody Magrolimab for AML had been temporarily halted by the FDA. At that time, the screening and enrollment of new study participants under Investigational New Drug (IND 147229) and the Expanded Access Program in the United States were suspended, although the specific reasons remained unclear.

Magrolimab is a potential first-in-class anti-CD47 immunotherapy, primarily working by blocking inhibitory interactions between CD47-Signal Regulatory Protein Alpha (SIRPα), enhancing the ability of macrophages and other phagocytic cells to recognize and eliminate foreign and malignant cells, effectively thwarting cancer cells’ “don’t eat me” signals.

Gilead: CD47 Antibody Development Hit by Second Phase III Trials Termination

Figure 1: About Magrolimab ( Source: Gilead official website)

The product was acquired by Gilead in a $4.9 billion deal with Forty Seven in 2020, solidifying its leadership position in the CD47 target space. With high hopes vested in this costly acquisition, Gilead had high expectations for Magrolimab. However, despite an initial glimmer of promise, its development has encountered successive setbacks.

While CD47 is considered a potential avenue for blood cancer treatment, its clinical efficacy has yet to be firmly established. After signing a $2 billion deal in 2020, AbbVie and its partner, Tenebio, decided to halt the Phase Ib trial of lemzoparlimab due to a lack of evidence supporting further dose escalation. This week, AbbVie terminated the licensing and collaboration agreement with Tenebio in an effort to minimize losses.

Celgene had also been considered a frontrunner in the CD47 antibody market, but they terminated the Phase I trial of CC-90002 in 2018 due to the preliminary data in AML and MDS failing to provide evidence for further dose escalation.

Despite the rocky road in CD47 antibody research, Gilead has not given up on Magrolimab entirely. The antibody is currently being investigated in the ENHANCE-3 study for frontline AML patients, but this trial remains in partial clinical hold to prevent new patients from enrolling. Additionally, it is being studied in diffuse large B-cell lymphoma and solid tumors such as triple-negative breast cancer, brain cancer, and head and neck squamous cell carcinoma, among others.

Gilead: CD47 Antibody Development Hit by Second Phase III Trials Termination

Magrolimab clinical development plan covers ten potential indications (Source: Gilead official website)

Gilead: CD47 Antibody Development Hit by Second Phase III Trials Termination

Reference:
[1] Gilead Axes Phase III Magrolimab Trial Based on Disappointing Data. Published: Sep 27, 2023 By Kate Goodwin.
[2] Gilead Official Website.

(source:internet, reference only)


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