In the United States, the FDA grants Fast Track designation to drugs that treat rare and serious conditions or fill unmet needs. The designation helps to facilitate and expedite the drug’s development and review. When a drug company receives Fast Track designation, they also earn benefits such as more frequent FDA meetings and communication, Rolling Review, and Accelerated Approval and Priority Review eligibility. According to a press release from pharmaceutical company Karyopharm Therapeutics (“Karyopharm”), the company’s product selinexor, designed to treat myelofibrosis, earned Fast Track designation. 

Selinexor is a first-in-class, orally administered selective inhibitor of nuclear export (SINE) compound. Karyopharm explains that selinexor works by:

binding with, and inhibiting, the nuclear export protein, XPO1, leading to the accumulation of tumor suppressor proteins in the cell nucleus. This reinitiates and amplifies their tumor suppressor function and is believed to lead to the selective induction of apoptosis in cancer cells, while largely sparing normal cells.

It is already marketed as XPOVIO in the U.S. and indicated for the treatment of multiple myeloma and diffuse large B-cell lymphoma. 

Now, researchers are evaluating selinexor for primary myelofibrosis, post-essential thrombocythemia myelofibrosis, and post-polycythemia vera myelofibrosis. Prior data highlights the benefits of 60mg selinexor in relieving symptoms. 

The Phase 3 XPORT-MF-034 study launched in June with a goal of understanding the therapy’s safety and efficacy when used in conjunction with ruxolitinib. In particular, the study is exploring this therapeutic combination for people with myelofibrosis who have not previously been treated with JAK inhibitors. Data from this study should be available in 2025. 

Understanding Myelofibrosis

Myelofibrosis is a rare bone marrow disorder caused by changes in a single hematopoietic stem cell. This stem cell then continues to make copies of itself, pushing healthy cells out of the bone marrow. JAK2, CALR, and MPL genes have been implicated in myelofibrosis, though the exact role they play is unknown. Myelofibrosis is characterized by abnormal blood cell production and bone marrow scarring. This disorder is more common in people ages 50 or older. If it occurs in children, it is 2x more common in girls than boys and often manifests before three years old.

Symptoms may, but do not always, include:

• Anemia (low red blood cell counts) 
• Fever and night sweats
• Frequent or recurrent bacterial and fungal infections
• Shortness of breath
• Fatigue and general weakness
• Excessive and abnormal bruising and bleeding 
• An enlarged spleen and liver
• Lightheadedness
• Pulmonary hypertension 
• Headaches
• Blood clots
• Pale skin
• Irritability
• Abdominal fullness
• Joint and bone pain 

Ruxolitinib, blood transfusions, stem cell transplants, and androgen therapy are just four of the potential treatment options for this condition.