New cancer drug associated with KU Leuven discovery approved in the US

The Food and Drug Administration in the United States of America has approved XPOVIOTM (also known as selinexor), a medicine for patients with relapsed refractory multiple myeloma, a type of bone marrow cancer. Around 230,000 people worldwide suffer from this rare disease. Selinexor was developed by Karyopharm Therapeutics Inc. based on inhibitors discovered at KU Leuven. 

Multiple myeloma is a cancer of plasma cells. Plasma cells are white blood cells that produce antibodies to defend the body against infections. The disease usually occurs in people over 60 years old. There are several treatment options to control the cancer and prolong the life of patients, but multiple myeloma is as of yet incurable.

Myeloma patients with disease that is refractory to the most effective, currently available treatment options typically have a life expectancy of just three to five months. Results from a clinical trial demonstrated that patients with highly refractory multiple myeloma who were treated with oral selinexor lived over eight months, on average. Patients who responded to selinexor lived, on average, over fifteen months.    

Selinexor inhibits Exportin 1 (XPO1 or CRM1), a protein that is responsible for the transport of other proteins from the cell nucleus to the surrounding cytoplasm. These include proteins that suppress the growth of tumors. If these proteins are not present in the cell nucleus, they cannot perform their function. Inhibitors of XPO1 restore the localization of these tumor suppressing proteins, causing cancer cells to regress.

Professor Dirk Daelemans discovered XPO1 inhibitors in collaboration with Professor Christophe Pannecouque, both working at the Laboratory of Virology and Chemotherapy at the Rega Institute, and with Professor Wim Dehaen of the Department of Chemistry, and in 2011 signed a collaboration agreement with Karyopharm Therapeutics, which was developing XPO1 inhibitors.

"We discovered these inhibitors while studying the transport of viral genetic material of HIV in infected cells", explains Professor Daelemans. “Inhibiting XPO1 turned out to be less appropriate for the treatment of HIV infections, but it is of use for cancer. This is an excellent example of how we can use our knowledge about viruses in the treatment of other life-threatening diseases. Selinexor is the first drug of its kind to be approved by the FDA. We are very happy about the collaboration with Karyopharm and the tremendous amount of work they have done to develop this medicine. Many patients can now be helped as a result of their work."

Professor Daelemans’ team and the Center for Drug Design and Discovery (CD3) at KU Leuven are now studying the reverse process, in which proteins are transported into the cell nucleus. This knowledge could be used for potential new therapies for cancer or other diseases.

Selinexor is now available in the United States for the treatment of patients with relapsed or refractory multiple myeloma who have been treated with at least four prior therapies. The drug has also been submitted to the European Medicines Agency for approval. Their decision is expected at the end of this year.

In addition to multiple myeloma, selinexor also shows promising activity on other types of cancer, such as a form of lymphoma, endometrial cancer and liposarcoma, a tumor of fat cells. For these applications, selinexor is currently being evaluated in clinical trials of which the endometrial trial (SIENDO) is lead by Professor Ignace Vergote, Head of the Department Gynaecology and Obstetrics at the University Hospitals Leuven. Depending on the results, the drug could be approved for these additional indications in the coming years. Multiple additional indications and combination regimens are also in clinical development through investigator sponsored trials. Related XPO1 inhibitors are also being investigated for other therapeutic applications.

This communication was first published 9 July 2019 by KU Leuven.