Update on the Drug Development Pipeline for Myeloma

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In this video, Dr. James Berenson discusses the 10-year myeloma survival data presented at ASH 2011 and covers a large number of drugs that are nearing an FDA decision as well as treatments that are further upstream.  For patients interested in the science of how these drugs work, Dr. Berenson shares his insight and his excitement about this point in time for myeloma treatment

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

Similarly, we’ve had Velcade for the last eight or nine years as the only proteasome inhibitor, only one in that class that we’ve been able to use effectively and FDA approved, but it’s clear now that there are newer agents, a number of them in development.  One in very late development, carfilzomib, is very active, especially being studied in the relapsed/refractory setting and even looks possibly more active than Velcade, although we don’t know that for sure, but we are now seeing activity in patients that are very refractory to Velcade with a drug we thought was a twin.  It turns out, no, it’s not just like thalidomide and lenalidomide, failing thalidomide you get lenalidomide or failing lenalidomide you get thalidomide, we’re now seeing Velcade failures who are dramatically responding to similar drug combinations with carfilzomib.  We just opened up a whole opportunity for patients now to get a whole bunch of drugs.  Because, remember, Velcade can be combined with a slew of different drugs.  We’re now seeing the same thing with carfilzomib.  Even among failures again to Velcade combinations, this is a drug. 

There are a lot of other drugs in early development in that same class, oral agents such as 9708 from millennium, the Nereus product, NPI-0052 and there also is a product from the group at Cephalon called CEP-18770.  These are in early trials, some suggestions of activity in our laboratory and we published data and are publishing more.  These are very exciting molecules.  Some of them appear to overcome Velcade resistance, in the laboratory at least, like we’ve seen in carfilzomib and Velcade failures. 

In terms of other types of drugs we have very good data only in the laboratory at this point, but which is a drug like DOXIL but in which you can give much more of this drug called INNO, or I-N-N-O, 206.  It’s a drug that is similar to doxorubicin but it’s only released in the acid pH environment of tumors.  So in your blood it’s bound to albumin, it’s inert, it doesn’t work.  But when it gets in the tumor, boom.  So in our animal models you can give a lot more of this than conventional doxorubicin, and at least in the phase 1 trials you can give four and five times the amount of conventional doxorubicin or Adriamycin of this new agent.  We hope to get into trials in myeloma combining it with either Velcade or carfilzomib in 2012. 

There also are antibodies that are moving along, particularly the elotuzumab story.  This is an antibody, the CS-1 or mucin which is expressed on myeloma cells and although as a single agent there’s a very small activity, once you combine that, especially as presented here at the meeting, with lenalidomide or Revlimid and steroids, very high response rates.  And whether that’s adding to Revlimid and dexamethasone beyond what the activity of those two have alone we’re going to see in large phase 3 trials.  There’s data with antibodies, the CD-138 that was just presented at the meeting, and there’s also more data emerging with a number of other targets such as perifosine a PI3 kinase inhibitor, as well as a number of HDAC inhibitor studies, not alone but combined with either chemotherapy or Velcade.  In the laboratory Velcade and these HDAC or histone deacetylase inhibitors are very active.  Clinically there are now trials, phase 3s that are being done based on promising phase 2s that are being presented at this meeting as well. 

There also is more data emerging that we and others have done with a drug called bendamustine, a drug very, very active in lymphoma and chronic lymphocytic leukemia.  It’s not been really well studied yet or until recently in myeloma, but we’ve done studies with Velcade that we’re about to submit for publication presented at these meetings before and earlier this year at ASCO as well as with lenalidomide and steroids with bendamustine.  It looks very promising. 

And similar to what I said earlier with Thalomid to Revlimid to pomalidomide, we are seeing a similar story with alkylating agents, melphalan failures can respond to cyclophosphamide, and now we have another drug they can respond to, bendamustine in combination it looks like, with lenalidomide and steroids or in combination with Velcade. 

So lots of new opportunities for patients now.  We really have patients now in trials that have seen 15 and 20 prior regimens.  We would have never dreamed about that even five years ago and patients with excellent quality of lives. 

In a similar vein you would think that patients in the past who didn’t respond to one drug in a class, say, melphalan, and then they get another drug in that class called an alkylating agent, cyclophosphamide or bendamustine, they respond.  It’s pretty amazing.  And in a similar matter we thought that, oh, in five, seven years ago if you didn’t respond to Velcade it’s over, go to something else.  You can combine Velcade with many different drugs safely and effectively, and it’s really a matter of not giving up.  There’s more and more things to try in our patients today. 

 

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

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Page last updated on September 5, 2014