CIRM-funded treatment for cancer granted FDA breakthrough therapy designation

Mark Chao, M.D., Ph.D., cofounder of Forty Seven, Inc. and current VP of oncology clinical research at Gilead Sciences

An antibody therapeutic, magrolimab, being tested for myelodysplastic syndrome (MDS), a group of cancers in which the bone marrow does not produce enough healthy blood cells , was granted breakthrough therapy designation with the Food and Drug Administration (FDA). 

Breakthrough therapy designations from the FDA are intended to help expedite the development of new treatments. They require preliminary clinical evidence that demonstrates that the treatment may have substantial improvement in comparison to therapy options currently available. CIRM funded a Phase 1b trial in MDS and acute myeloid leukemia (AML), another type of blood cancer, that provided the data on which the breakthrough therapy designation is based.

Cancer cells express a signal known as CD47, which sends a “don’t eat me” message to macrophages, white blood cells that are part of the immune system designed to “eat” and destroy unhealthy cells. Magrolimab works by blocking the signal, enabling the body’s own immune system to detect and destroy the cancer cells.

Magrolimab was initially developed by a team led by Irv Weissman, M.D. at Stanford University with the support of CIRM awards. This led to the formation of Forty Seven, Inc., which was subsequently acquired by Gilead Sciences in April 2020 for $4.9 billion (learn more about other highlighted partnership events on CIRM’s Industry Alliance Program website by clicking here).

In CIRM’s 2019-2020 18-Month Report, Mark Chao, M.D., Ph.D.,  who co-founded Forty Seven, Inc. and currently serves as the VP of oncology clinical research at Gilead Sciences, credits CIRM with helping progress this treatment.

“CIRM’s support has been instrumental to our ability to rapidly progress Forty Seven’s CD47 antibody targeting approach.”

Magrolimab is currently being studied as a combination therapy with azacitidine, a chemotherapy drug, in a Phase 3 clinical trial in previously untreated higher risk MDS. This is one of the last steps before seeking FDA approval for widespread commercial use.

Merdad Parsey, MD, PhD, Chief Medical Officer at Gilead Sciences

In a press release, Merdad Parsey, M.D., Ph.D., Chief Medical Officer at Gilead Sciences discusses the significance of the designation from the FDA and the importance of the treatment.

“The Breakthrough Therapy designation recognizes the potential for magrolimab to help address a significant unmet medical need for people with MDS and underscores the transformative potential of Gilead’s immuno-oncology therapies in development.”

CIRM funded clinical trial shows promising results for patients with blood cancers

An illustration of a macrophage, a vital part of the immune system, engulfing and destroying a cancer cell. Antibody 5F9 blocks a “don’t eat me” signal emitted from cancer cells.
Courtesy of Forty Seven, Inc.

Myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) are both types of blood cancers that can be difficult to treat. CIRM is funding Forty Seven, Inc. to conduct a clinical trial to treat patients with these blood cancers with an antibody called 5F9. CIRM has also given multiple awards prior to the clinical trial to help in developing the antibody.

Cancer cells express a signal known as CD47, which sends a “don’t eat me” message to macrophages, which are white blood cells that are part of the immune system designed to “eat” and destroy unhealthy cells. The antibody works by blocking the signal, enabling the body’s own immune system to detect and destroy the cancer cells.

In a press release, Forty Seven, Inc. announced early clinical results from their CIRM funded trial using the antibody to treat patients with AML and MDS. Some patients received just the antibody while others received the antibody in combination with azacitidine, a chemotherapy drug used to treat these cancers.

Here is a synopsis of the trial:

  • 35 patients treated in a Phase 1 clinical trial have been evaluated for a response assessment to-date.
  • 10 of these have MDS or AML and only received the 5F9 antibody.
  • 11 of these have higher-risk MDS and received the 5F9 antibody along with the chemotherapy drug azacitidine.
  • 14 of these have untreated AML and received the 5F9 antibody along with the chemotherapy drug azacitidine.

For the 11 patients with higher-risk MDS treated with the antibody and chemotherapy, they found that:

  • All 11 patients achieved an objective response rate (ORR), meaning that there was a reduction in tumor burden of a predefined amount.
  • Six of these patients achieved a complete response (CR), indicating a disappearance of all signs of cancer in response to treatment.

For the 14 patients with untreated AML treated with the antibody and chemotherapy, they found that:

  • Nine of these patients achieved an ORR.
  • Five of these nine patients achieved a CR.
  • Two of these nine patients achieved a morphologic leukemia-free state (MLFS), indicating the disappearance of all cells with formal and structural characteristics of leukemia, accompanied by bone marrow recovery, in response to treatment. 
  • The remaining five patients achieved stable disease (SD), meaning that the tumor is neither growing nor shrinking.

The results also showed that:

  • There was no evidence of increased toxicities when the antibody was used alongside the chemotherapy drugs, demonstrating tolerance and safety of the treatment.
  • No responding MDS or AML patient has relapsed or progressed on the antibody in combination with chemotherapy, with a median follow-up of 3.8 months.
  • The median time to response was rapid at 1.9 months.
  • Several patients have experienced deepening responses over time resulting in complete remissions. 

Based on the favorable results observed in this clinical trial to-date, expansion cohorts have been initiated, meaning that additional patients will be enrolled in a phase I trial. This will include patients with both higher-risk MDS and untreated AML as well as using the antibody in combination with chemotherapy.

In the press release, Dr. David Sallman, an investigator in the clinical trial, is quoted as saying,

“These new data for 5F9 show encouraging clinical activity in a broad population of patients with MDS and AML, who may be unfit for existing therapeutic options or at higher-risk for developing rapidly-advancing disease. Despite an evolving treatment landscape, physicians continue to seek new therapies for MDS and AML that can be used safely in combination with standard-of-care to help patients more rapidly achieve durable responses. To that end, I am excited to see meaningful clinical activity in a majority of patients treated with 5F9 in combination with azacitidine, with a median time to response of under two months and no relapses or progressions among responding patients.”