Sometimes, it can be difficult to prompt the research of and creation of therapeutics for rare diseases. This is one of the reasons why the FDA created its Orphan Drug program. The FDA grants Orphan Drug designation to drugs or biologics intended to treat, prevent, or diagnose rare diseases – those affecting under 200,000 Americans. If a company receives this designation for one of its products, the company also receives a variety of benefits, including fee waivers, tax credits, increased regulatory assistance, and seven years of market exclusivity upon approval. According to a recent news release from Sumitomo Pharma Oncology, Inc., a subsidiary of biopharmaceutical company Sumitomo Pharma, the FDA recently granted its product TP-3654 Orphan Drug designation for the treatment of myelofibrosis. 

What is TP-3654?

An article published in the International Journal of Molecular Science describes TP-3654 as:

an experimental second-generation inhibitor of PIM kinase that…resensitizes ABCG2-overexpressing multidrug-resistant cancer cells to cytotoxic ABCG2 substrate drugs.

This orally administered treatment, which is being evaluated for myelofibrosis and other forms of cancer, is considered to have both anti-tumor and anti-fibrotic effects. TP-3654 could cause cancer cell apoptosis (cell death), leading to better patient outcomes. In short, researchers believe that PIM kinases could act as a therapeutic target for myelofibrosis.

Currently, researchers are testing these hypotheses within Phase 1 and Phase 1/2 clinical studies. The first study is evaluating TP-3654 for solid tumors, while the second study is evaluating TP-3654 for myelofibrosis specifically. As preclinical studies have found that TP-3654 reduced bone marrow fibrosis and spleen size in animal models of myelofibrosis, researchers are hopeful that it will confer similar benefits to humans. 

Myelofibrosis: An Overview

Myelofibrosis is a rare and chronic form of leukemia and is also considered to be a bone marrow disorder. There have been a number of genes implicated in myelofibrosis: JAK2, CALR, and MPL. However, the genetic mutation(s) which cause myelofibrosis are considered to be idiopathic and occur without a known cause. Regardless, myelofibrosis causes a hematopoietic stem cell to continually replicate. These abnormal cells crowd healthy cells out of the bone marrow. Additionally, myelofibrosis causes bone marrow fibrosis (scarring), which also prevents the bone marrow from creating enough healthy blood cells. 

Typically, myelofibrosis occurs in those aged 50+, though it can occur in younger individuals. In children, this condition occurs 2x more often in females than males. When symptoms appear, these can include:

• Anemia (low red blood cell count)
• Pallor (pale skin)
• Fever and night sweats
• Frequent infections
• Tumors in the lungs, skin, liver, spleen, etc. 
• Shortness of breath
• General weakness
• Headaches and lightheadedness
• Irritability
• Easy and excessive bruising and bleeding
• Enlarged liver and spleen
• Bone and joint pain