In the first of a three-part interview at ASH 2013 with Dr. John Byrd, my personal trial physician from Ohio State, we look at the drug, dinaciclib, a cyclin-dependent kinase (CKD) inhibitor, similar to flavoperidol that arrests tumor proliferation. Flavoperidol is a potent but difficult drug to administer with a very nasty attitude. For many with 17p deletion, it was their only chance at a remission. Dinaciclib is a kinder gentler drug, with a better safety margin or “therapeutic index”. Dinaciclib also works independent of the 17p pathway and so has potent activity in that most difficult to treat population.
The ASH 2013 abstract is available here. I attended the oral presentation on the last day of ASH 2013 in New Orleans. Dr. Joe Flynn, also out of OSU, was the lead investigator and just one of the nicest guys ever. Another great CLL doctor we patients are blessed to have.
So what did the phase 1 trial data show us about this IV drug’s effect for these 52 most difficult to salvage patients?
Its impressive efficacy of 58% is essentially the same (57%) in the 17p and 11q group. Responses were also very durable. Tumor lysis syndrome was a small but real risk and there was one case of sepsis. The most common side effects were low blood counts (leucopenia, anemia, and thrombocytopenia). That fits with how it works as a CKD inhibitor.
Sounds pretty good, but I bet you have never heard of it. And it will probably never become commercially available, even though it helped nearly 6 out of every 10 of the worst relapsed/refractory patients with 17p deletion who until very recently had very few real options.
It likely won’t be marketed in part because it’s given IV, but more importantly, because the new oral agents such as ibrutinib and idelalisib and ABT-199 and others have similar or better efficacy with fewer risks.
The bar has been set very high.
It’s a business decision. Merck who owns the patent on the drug must compare the high cost to get to this new molecule to market with the shrunken market share when and if does get there.
While I understand and appreciate that every company must make decisions that are sensitive to their long-term success and viability, these decisions are sometimes (such as in this case) not the best for us patients.
As we get near the end of this segment of the interview, Dr. Byrd discusses the early research on the causes of resistance in the few patients, especially the 17p patients that do relapse on ibrutinib.
We patients need as many options as possible to help us in those desperate circumstances.
Dinaciclib could have been a potent option.
I am glad that ibrutinib, idelalisib and ofatumumab are approved.
But we mustn’t stop there. The CLL battle is going well, but it is hardly won. This is no time to let up on the research and equally important, the commercial development of these novel molecules.
Don’t leave us patients stranded on third base.
Listen to our conversation from Dec 2013 on this and other topics:
There are two more informative interview segments with Dr. Byrd from the last day of ASH 2013.
I was going to write that the CLL story is in evolution, but in truth it is in revolution.
It helps me to understand these rapid changes by reviewing all the research steps that lead to progress or to blind alleys.
Brian Koffman 6/11/14. Revised 3/17/15