Striving to Change the Trajectory
of Myelofibrosis
Myelofibrosis – which belongs to a group of diseases called myeloproliferative disorders – is a difficult-to-treat form of blood cancer that’s characterized by bone marrow fibrosis (a buildup of scar tissue in the bone marrow), an enlarged spleen, and anemia (low blood counts) often requiring a blood transfusion. Patients with myelofibrosis can also suffer from a range of physical symptoms, including fatigue, night sweats, itching, increased bleeding risk, and significant pain caused by their enlarged spleen. For many living with myelofibrosis, the multiple symptoms combine to create a “perfect storm” of disease that often severely impacts their quality of life.
At diagnosis, several factors can help determine a patient’s long-term prognosis, such as age, genetics, and bloodwork. About 90% of newly diagnosed patients are found to have intermediate- to high-risk myelofibrosis, which has a worse prognosis and a higher likelihood of disease-associated symptoms.
Today, myelofibrosis treatments revolve around the use of medications called JAK inhibitors, which focus on relieving symptoms of myelofibrosis rather than treating its cause. But with this strategy, only about 50% of patients achieve adequate symptom control, and unfortunately, for many, that relief fades with time. People suffering from myelofibrosis are in critical need of treatment options that not only address their symptoms but also act to change the overall course of their disease.
At MorphoSys, our work is focused on proteins called bromodomain and extra-terminal domain (BET), which are associated with myelofibrosis progression. Pre-clinical studies suggest that combining JAK inhibitors with medications that block BET proteins (BET inhibitors) may not only improve the symptoms of myelofibrosis, such as by reducing spleen size, but also potentially treat the cause of the disease. At the American Society of Hematology 2022 Annual Meeting and Exposition, we presented clinical data from a subset of myelofibrosis patients in our ongoing Phase 2 MANIFEST study who had never received JAK inhibitor therapy. These findings suggest that our BET inhibitor in combination with a JAK inhibitor may provide prolonged improvement in both spleen size and symptom severity at and beyond 24 weeks.
“We’re working diligently to gather data on our BET inhibitor that may enhance the standard of care for myelofibrosis so patients can benefit from deeper and more durable responses to therapy. Our ambition is to get to the root cause of the disease – modifying the disease itself – with the hope to help those currently impacted by this debilitating condition.”
Tim Demuth, M.D., Ph.D., Chief Research and Development Officer, MorphoSys
We anticipate that the topline data of our Phase 3 MANIFEST-2 study will be available in early 2024, and we are hopeful that this data will demonstrate the potential of a novel BET inhibitor to ease the suffering of myelofibrosis patients.
