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On the third day of ASH (American Society of Hematology) 2016 Conference in San Diego, I interviewed Mark Wildgust, PhD, Vice President, Global Medical Affairs, Oncology at The Janssen Pharmaceutical Companies of Johnson & Johnson concerning, what else, his company’s blockbuster molecule, ibrutinib.
Ibrutinib is shared with Abbvie and Pharmacyclics.
Dr. Wildgust is justly proud of and positively biased towards ibrutinib and the positive changes it has brought to the care of so many patients with chronic lymphocytic leukemia (CLL). He argues forcibly that other new molecules will need to be equally vetted and proven over time before jumping to the conclusion that they are as effective in chronic lymphocytic leukemia just because, like ibrutinib, they block BTK (Bruton’s Tyrosine Kinase) which is thought to be the main story of its potency.
By blocking BTK, ibrutinib blocks communication pathways and thus inhibits our cancerous B cells from receiving pro-survival and pro-proliferation signals from other cells. They eventually die.
But there may be much more to the story.
Take Away Points:
- All the strong survival data with ibrutinib (see: https://cllsociety.org/2017/01/ash-2016-real-world-ibrutinib-cll/), some of it more than 5 years out, was data for patients taking ibrutinib, not other BTK blockers.
- Ibrutinib blocks several other kinases (enzymes) besides BTK that may be important in CLL.
- One of these of particular interest is ITK (interleukin-2-inducible T-cell kinase) that may have an important positive effect on the behavior of our T cells that are dysfunctional in CLL. Ibrutinib may improve this.
- Recent research suggests that the indirect effects of ibrutinib on the cancer cell through changes in its micro-environment might be critical in its efficacy.
We do know that when ibrutinib loses the ability to bind to the BTK receptor and thus to potently block the CLL cell’s signaling, its efficacy is markedly diminished so surely BTK inhibition is critical to its power to control CLL, but is there more to the story?
Only further research will tell.
That is why that I am excited to hear that Janssen is still pushing ahead with several more trials on ibrutinib.
That is why that I am also excited that other companies such as Astra Zeneca (acalabrutinib), Sunesis (SNS-062), ONO and Gilead (ONO/GS-4059), Beigene (BGB-3111) and others are working hard to see if they can prove their drugs offer equal or different benefits compared to ibrutinib.
That is why we need clinical trials. It can only benefit us.
Here is my interview with Dr. Wildgust of Janssen. You can also read the transcript here.
We are all in this together
Brian Koffman, MD 7-11-17