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The Science Behind Selinexor: A First-In-Class Drug Approval

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Published on December 23, 2019

Key Takeaways

  • FDA pproval of selinexor (Xpovio) for multiple myeloma patients.
  • Selinexor is a first-in-class, orally administered medication.
  • FDA approved as a single agent with dexamethasone (Decadron) given twice weekly.

Patient advocate and host Cindy Chimelewski talks with Dr. Sundar Jagannath, from The Mount Sinai Medical Center, about the FDA approval of the first-in-class, orally administered medication selinexor (Xpovio). Dr. Jagannath provides an explanation of how it works to treat myeloma, the recommended dosage, and using it in combination with other drugs.

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Transcript | The Science Behind Selinexor: A First-In-Class Drug Approval

Please remember the opinions expressed on Patient Power are not necessarily the views of our sponsors, contributors, partners or Patient Power. Our discussions are not a substitute for seeking medical advice or care from your own doctor. That’s how you’ll get care that’s most appropriate for you.

Cindy Chmielewski:                         

The myeloma community is very excited about the approval of the new drug selinexor (Xpovio), but a lot of people don’t know a lot about what selinexor is. So, can you just get started about what it is. Is it a new mechanism in action? Just a little bit of background about selinexor. 

Dr. Jagannath:            

Yes, indeed. This is an exciting time for multiple myeloma patients. We got one more drug approved for the treatment of multiple myeloma. As they say, there’s more chocolate added to the box. And selinexor is a new drug, and it is an exciting new drug. This is a first-in-class, orally administered medication. The mechanism of action is completely new. That’s very important for us when a new drug comes in with a new mechanism of action that truly adds to the treatment of the material. This was called selinexor. It is selective inhibitor of Exportin-1. So, in layman’s terms, there is proteins shuttling between the nucleus and the cytoplasm.

As you all know, nucleus is where the DNA is, and all the necessarily information codes, they are in the DNA, and the DNA is protected in the cell, enveloped in its own sac. So, that’s call the nucleus. Then outside is the cytoplasm where all the protein making machinery is there. So, the message has to get from the genes, have to be transcribed. The genes are in the DNA in the nucleus. They are transcribed. They have to go to the cytoplasm, and then they will be made into protein. So, this transportational protein in and out of the nucleus to the cytoplasm is very critical.

Now, this is not just a passive transfer of the protein. They have to be actually transported, and that’s the function of Exportin. So, Exportin-1 is a chaperone molecule which chaperones the protein and helps it go from the nucleus in to the cytoplasm. Now, if you block it, now you see all the messages from the DNA don’t get to the cytoplasm and don’t get to become a protein. So, this is important. So, what happens is—especially Exportin is very important for cells which are multiplying, especially in cancer cells, so Exportin, the chaperone molecule, is expanded, especially in myeloma cells—cancer cells. There are numerous of them in the cancer cell.

So, they can get all the information required for the cell to continue to multiply. Now, if you drop the Exportin, then the signaling doesn’t happen. So, there are tumor suppressive protein. These are called the brakes which stop the cells from multiplying. Now, the cancer cells, what they do is they ship them out so they can keep multiplying. Now, if you block the transportation, then the tumor suppressive protein are reading within the nucleus and puts the brake on the cell from multiplying. So, that’s one kind. Then there are other important proteins like p53. It is a master gene. It is very important.

Anytime there is damage to the DNA, it reads it, and it immediately allows the cell to undergo suicide rather than allow it to multiply. But you know, cancer cells have a lot of genetic abnormality, so they don’t want this messaging that they like to ship them out and destroy them. By blocking this, you retain the p53, so that could realize that this is the cancer cell that has a genetic abnormality so it can undergo apoptosis. 

So, tumor suppressive protein don’t go in and out, so translation is inhibited, so the cancer cells become vulnerable and they die. This is a completely new mechanism, and the beauty is this is done by an oral pill, and that’s the beauty of this new drug. So, we are all excited it got the FDA’s nod. 

 

Cindy Chmielewski:                        

Good. So, is it taken every day, the oral pill, or is it taken once a week, or how often?

Dr. Jagannath:            

The way the drug is approved, it is approved as it was done in clinical trial. You were given 80 milligrams twice weekly, and it could be then, depending upon the tolerance, you can reduce the dose and still give it twice weekly or you can give it even once weekly. On the lenalidomide (Revlimid) clinical trial where bortezomib (Velcade) dexamethasone (Decadron) with or without selinexor, the clinical trials—international randomized clinical trial that has been completed, we are awaiting the results. 

So, that trial, they gave it once a week with Velcade. So, when you combine it, you can combine it with Velcade once a week. When it is used by itself, it could be given even twice weekly. So, currently, the FDA approved it as a single agent with the dexamethasone, so it’s selinexor plus dexamethasone given twice weekly.

Please remember the opinions expressed on Patient Power are not necessarily the views of our sponsors, contributors, partners or Patient Power. Our discussions are not a substitute for seeking medical advice or care from your own doctor. That’s how you’ll get care that’s most appropriate for you.

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