A ‘first-in-class’ therapy that recently received FDA Breakthrough Therapy designation in the U.S. for the treatment of newly diagnosed MDS will be available “very soon” to Australians in a clinical trial.

Magrolimab is an investigational anti-CD47 monoclonal antibody that is being studied in the randomised Phase III ENHANCE study which is evaluating the safety and efficacy of magrolimab in combination with azacitidine (Vidaza®) in higher risk MDS.

Professor Andrew Wei, haematologist at the Alfred Hospital (Melbourne), said magrolimab “was a potential important advance for patients with MDS” and “a treatment option with a highly novel mechanism of action”.

“Magrolimab activates specialised immune cells to recognise, engulf, and digest malignant cells,” with response rates in single arm early-phase trials “that are very promising”.

“Randomised clinical trial validation is now the next step,” said Dr Wei.

Dr Wei is on the global steering committee for the randomised studies in MDS and AML (in which magrolimab also has shown activity in poor risk patients) and is the principal investigator for the ENHANCE registration trial which is in the process of opening in hospitals across Australia.

The Alfred has just commenced recruitment for the trial, with other sites coming online over the next few months.

This means most eligible newly diagnosed patients with higher risk MDS should be able to access the trial “as long as they pass eligibility assessments”.

“There are other studies in this area as well, such as venetoclax plus azacitidine, which is also open to recruitment to patients with newly diagnosed MDS. The field has never been so active,” said Dr Wei.

Clinical haematologist, Professor Steven Lane, who heads a research laboratory at QIMR Berghofer Medical Research Institute (Brisbane) and whose focus is on myeloid disorders including MDS, has described magrolimab as “a super exciting drug”.

Dr Heshaam Mir, Medical Director Australia & New Zealand, Gilead Sciences, which has developed the drug, said, “magrolimab represents an alternative treatment for those patients with limited options”.

“But it is important to remember it is still an investigational medicine whose safety, efficacy, and clinical benefit have yet to be established.

“Magrolimab is not yet licensed or approved for any use by any regulatory authority.”

The FDA granted Breakthrough Therapy designation for magrolimab based on the positive results of an ongoing Phase Ib study, evaluating magrolimab in combination with azacitidine in previously untreated intermediate, high, and very high-risk MDS and AML.

In data presented at the 2020 European Hematology Society Congress, 91 per cent of evaluable MDS patients treated with magrolimab plus azacitidine achieved an objective response, with 42 per cent achieving a complete remission. The combination of magrolimab plus azacitidine was generally well-tolerated. No maximum tolerated dose was reached and no MDS patients discontinued treatment due to a treatment-related adverse event.

Breakthrough Therapy designation is designed to expedite the development and regulatory review of investigational treatments for serious or life-threatening conditions that, based on preliminary clinical evidence, have the potential to substantially improve clinical outcomes compared with available therapy.

“The Breakthrough Therapy designation recognises the potential for magrolimab to help address a significant unmet medical need for people with MDS,” said Dr Merdad Parsey, Chief Medical Officer, Gilead Sciences.

Magrolimab is a monoclonal antibody against CD47, a protein that works as a ‘don’t eat me’ signal used by cancer cells to avoid being ingested by macrophages — a kind of immune cell that engulfs invaders.

The investigative therapy works in a similar way to checkpoint inhibitors, but instead of activating T-cells, it improves the ability of macrophages to identify and eliminate cancer cells.

Because this evading mechanism is used by several cancer types, magrolimab represents a promising approach for a wide range of solid and blood cancers. Magrolimab has already received fast track status for diffuse large B-cell lymphoma and follicular lymphoma.

Speak to your haematologist regarding your eligibility and referral to the trial. For further information, contact the Alfred Hospital trial manager, Nola Kennedy, on ph: 03 9076 2217 or email: [email protected]