Multiple Myeloma February 2012

Hematology / Oncology Thought Leader Panel #29

 

 

Okay, so ASH 2011 is behind us.  It was a terrific meeting for multiple myeloma.  I had a chance to speak with a great group of Thought leaders just after the meeting and hear their views on many of the drugs and trials that were the talk of the meeting.  At the bottom of the blog, I’m including an excerpt from this Advisory Board.  But if you want the report and transcripts of those discussions in their entirety, they are available through the “Buy Now” link on BOLT’s home page.  See: Hematology / Oncology Thought Leader Panel #29  Multiple Myeloma 2012-01


Therapeutic Area: Hematology / Oncology

Disease Area(s): Multiple Myeloma

Specialty/Location: Hematology / N. America; Europe

Publication Date: January 2012

Principal Authors: Kim Grant, Tricia L. Hanlon, Jeffrey D. Berk, PhD, MBA

Product Code: MM#29-2012-01

 

 

Hematology-Oncology Thought Leader Panel #29, published January 2012, captures the opinions of 6 experts (5 US, 1 German) who specialize in multiple myeloma.  They provide insight into the practice-changing ramifications of the data presented at ASH 2011.

 

 

Mechanisms of action discussed in this report include proteasome inhibition, IMiD, HDAC, CS-1, CD38, CD58, CD138, FcHR5 / TAHO 18 / TAHO 38, FGF3, HSP90, AKT, MEK, IL6 and stem cell mobilization.

 

Drugs discussed in this report:

Company Generic Brand
Acetylon ACY-1215
AstraZeneca AZD-6244
Bristol-Myers Squibb / AbbottBMS elotuzumab; HuLuc63tanespimycin
Celgene lenalidomidepomalidomideromidepsin

marizomib / NPI-0052

RevlimidActimidIstodax
Centocor / Janssen CNTO-328
Cephalon Delanzomib; CEP18770
Genentech FcHR5 MAb
GenMab daratumumab; HuMax-CD38
Genzyme / Sanofi-Aventis plerixafor Mozobil
GlaxoSmithKline GSK2110183
ImmunoGenBioTest  / ImmunoGen lorvotuzumab; IMGN901BT-062
Keryx / Aeterna Zentaris perifosine
Merck vorinostat Zolinza
Millennium / Takeda bortezomibMLN-9708 Velcade
Nereus NPI-0052
Novartis panobinostatdovitinibAUY-922
Onyx ONX-0912
Proteolix / Onyx carfilzomib

 

 

So here are some of BOLT’s Panelists’ thoughts on marizomib (NPI-0052; Nereus / Celgene)

 

  • Celgene has accessed marizomib, giving them an exciting proteasome inhibitor to compliment their IMiD and HDAC options in myeloma. NPI-0052 is an irreversible proteasome inhibitor derived from Salinispora.  It appears to be extremely potent, probably one of the most potent PIs studied thus far.  Early US trials dosed once-weekly were negative in the salvage setting, but twice weekly dosing (Australian trial) showed responses in 4/16 highly refractory patients.

 

 

“Did Nereus present anything on theirs?  Nereus did.  They presented on their drug.  The interesting thing on that one is that it has basically been abandoned – they showed some data from Australia.  We had given it once weekly without activity, but when the Australians’ gave it twice weekly they’ve got four out of sixteen patients.  So it looks like here it is showing responses and that it has got activity.

 

“The preclinical work has been done already with the team in San Diego, but our clinical group has already connected with Nereus.  I put him in touch with Mike Palladino who is a real hot shot actually; he is excellent.  He is someone I have a lot of respect for.  I particularly like Kobi Sethna.  He is a generally principled man and a really good person.  As long as he can keep the fiscal operation afloat he can hopefully go forward.  I hope that they are working out some relationship with Celgene, which is looking quite promising vis-à-vis support.  So I think hopefully Celgene will have the wherewithal to see the opportunities in other tumors”.

 

 

  • It is also the only PI that penetrates the blood-brain-barrier, making it an extremely interesting therapy beyond myeloma; for glioblastoma.  There has been some neurotoxicity associated with marizomib, like hallucinations, cognitive changes and dizziness.  These are not usually seen with PIs, but this is probably related to the unique property of marizomib to penetrate into the CNS.  The combination of an IMiD + PI is very intriguing for glioblastomas.

 

“The preclinical work has been done already with the team in San Diego, but our clinical group has already connected with Nereus.  I put him in touch with Mike Palladino who is a real hot shot actually; he is excellent.  He is someone I have a lot of respect for.  I particularly like Kobi Sethna.  He is a generally principled man and a really good person.  As long as he can keep the fiscal operation afloat he can hopefully go forward.  I hope that they are working out some relationship with Celgene, which is looking quite promising vis-à-vis support.  So I think hopefully Celgene will have the wherewithal to see the opportunities in other tumors”.

 

 

 

“The knock against is that it has some side effects like hallucinations, cognitive changes and dizziness.  There is some neurotoxicity that we don’t usually see with this class of drugs.  So that may be a knock against it going forward”.

 

“It is very interesting to me and I think in the aggregate there are some very interesting properties of marizomib that set it apart.  One is that it clearly crosses the blood-brain barrier.  That is an important step forward.  We have actually connected Nereus with our brain tumor group led by Patrick Wen.  That is huge step forward.  Glioblastomas do not have a proteasome inhibitor that gets into them and glios are sensitive to proteasome inhibition.  And we already have the preclinical data for it.  If you think about it immune modulators already are used against glio – the IMiDs.  So there is a sort of sweet partnership here between IMiD and proteasome inhibition that could really revolutionize small molecule approaches in glioblastoma, which at the end of the day is as big a deal as myeloma, if not more.  So I think marizomib has…

 

 

 

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One Response to Multiple Myeloma February 2012

  1. Elvira says:

    Cancer itself is a dngoeraus disease. Bone cancer an be of different nature. Pain is the very common symptom of bone cancer. So whenever someone feels pain, should rush to doctor. Surgery, chemotherapy and radiation therapy, bone allografts, physiotherapy are some of the treatments suggested. For information different types of cancer, refer

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