The Value of research in fighting Leukemia: Menarini’s commitment to developing new therapies

For patients with leukemia – a cancer which affects the blood cells – effective and safe treatments are essential. For this reason, Scientific Research is constantly committed to developing innovative therapies that can make a difference to the lives of leukemia patients.

In this article, we have described the main characteristics of Acute Myeloid Leukemia, as well as focusing on Menarini’s commitment in the fight against hematological tumors, through research activities aimed at developing effective and innovative therapies which can make a real difference to the lives of patients.

Acute myeloid leukemia: what is it?

Acute myeloid leukemia (AML) is an aggressive malignancy characterized by an uncontrolled proliferation of red blood cells-, white blood cells-, and platelet- precursors in bone marrow. In patients with AML, the precursors do not complete their maturation process, but acquire the pathological ability to replicate in an uncontrolled way, thus producing cancer cells – called blasts or leukemia cells –which accumulate in the patient’s bone marrow and blood.

Although different risk factors exist for AML, in the majority of patients the disease originates in the absence of predisposing factors; on the other hand, genetic and/or molecular abnormalities acquired (i.e. non- inherited) from leukemic blasts can be frequently detected.

The treatment of AML depends on the characteristics of the disease (for example the presence or absence of mutations targeted by specific medicines) and those of the patient (age, other concurrent diseases, etc.), but, in general, all the different approaches have the common aim to eliminate – or at least to reduce – the uncontrolled growth of blasts. 

The evolution of therapies thanks to Scientific Research

Today chemotherapy and, in some specific cases, bone marrow transplantation are the main therapeutic choices made in the fight against AML; however, thanks to Scientific Research, in recent years, important steps forward have been made in the development of new therapies. The use of “intelligent” medicines has increasingly spread. These high-tech drugs are capable of acting on the cancer cells by targeting specific alterations of blasts or by exploiting the immune system making it attack the disease. Such a revolution has also been made possible thanks to the latest generation technologies, which provide a more detailed analysis of the genetic and molecular profiles of the blasts. The challenge we are facing today is being able to make new intelligent molecules available. These, either alone or, wherever possible, combined with conventional treatments, can maximize therapeutic efficacy whilst maintaining an  appropriate  safety profile.

Menarini’s commitment to developing new and innovative therapies

It is precisely on the development of innovative cancer therapies that the researchers at Menarini are channeling their efforts. In particular, two different molecules for the treatment of AML are currently undergoing clinical development.

MEN1703 is a small molecule discovered by Selvita (now known as Ryvu Therapeutics), capable of blocking two enzymes (PIM and FLT3) involved in the progression of AML. This experimental drug is currently undergoing clinical development as part of a phase I/II study (DIAMOND-01) being conducted in the United States. Several European research centers are also expected to participate in the study shortly. The first part of the study, which was aimed at determining the maximum tolerated dose of the drug in AML patients, recently came to an end and the key findings were presented at the 25th Congress of European Hematology Association (EHA).

The collaboration between Menarini and Oxford BioTherapeutics has led to the clinical trial of the MEN1112 monoclonal antibody, capable of recognizing cells leukemia through a specific protein present on their surface (CD157). MEN1112 induces a cytotoxic response mediated by the patient’s immune system which, by attacking blasts containing CD157, kills abnormal cells (ADCC, antibody-dependent cellular cytotoxicity). The ARMY-1 clinical study, conducted on AML patients, is currently on-going in several European research centers.

In addition to this, thanks to an exclusive licensing agreement undertaken with Swiss pharmaceutical group Helsinn, Menarini has also added Pracinostat, an oral inhibitor of the enzyme histone deacetylase (HDAC) of classes I, II and IV, to its pipeline. An international Phase III clinical study is currently on- going which foresees the administration of Pracinosat in combination with azacitidine to newly diagnosed adult AML patients, who for either age-related reasons and/or concurrent diseases, are deemed unsuitable for standard chemotherapy. Pracinostat, once again in combination with azacitidine, is also currently undergoing clinical development for the treatment of patients with higher risk myelodysplatic syndrome (SMD) in a Phase II clinical trial.

In closing, we are pleased to report below a short declaration made by Simone Baldini, Physician, Researcher and Senior Clinical Development Leader at the Menarini Research Hematologic Malignancies Department. Simone has dedicated much of his working life to the fight against leukemia and to the research and development of a treatment to target the disease.

“Thanks to both academic and industrial research, the fight against AML has risen from being a «mere» description of the characteristics of the disease – with the hope that these could be useful in improving treatment – to the possibility of developing increasingly targeted approaches to not only the patients’ AML condition but also their overall wellbeing”, explained Simone. “The enormous efforts made by both academic and industry-related researchers can lead to increasingly intelligent and personalized therapeutic approaches. I consider myself both lucky and honored to be able to fulfill my commitment to fight this disease to the full. I have worked in both hospitals and in universities, and I am currently a researcher in the pharmaceutical industry, so I feel I can make a positive contribution with the wonderful professional and personal experience I have gathered over the years. Scientific research has always been, and will continue to be, by the patients’ side and that of their families, making diseases like these more and more treatable”.