Topics Alert

A Bullseye on Rituxan

Date: July 28, 2024

One of the side effects of being the undisputed “king” of the anti-CD20 monoclonal market is that everyone would like to take a pot shot at the king. I guess it goes with the territory, but I can well imagine Genentech, the marketer of Rituxan, must be feeling just a little persecuted these days.

I hope you folks have read the latest article we published on the large multi-center Phase-III clinical trial of HuMax-CD20. This new anti-CD20 monoclonal from Genmab may be able to do tricks that Rituxan cannot, especially in refractory CLL patients. Just in case you have been a tad slow in catching up with your reading, here is the link to the Humax article:
A Smarter Monoclonal on Trial.

Well, it never rains but it pours. Eli Lilly has just initiated a phase I/II trial for yet another fully humanized anti-CD20 monoclonal. But unfortunately the inclusion criteria restrict participation to NHL patients only. They claims to have 10 times better ADCC pathway of cell kill than Rituxan. Here's the clinical trials link: Listing on ClinicalTrials.gov. I have written to the Lilly representative to see if we can get them interested in looking at us poor cousins over here in the CLL world, but “cold” emails are not often answered by drug companies busy making a buck. If any of you have contacts within Eli Lilly, please do help and introduce us. Like the proverbial camel, all I need is to get my nose in the tent, I can take it from there.

This new anti-CD20 is called AME-133. The following is a link to a presentation by Jim Breitmeyer of Applied Molecular Evolution. It looks like they have licensed AME-133 to Lilly.
Breitmeyer Presentation.

I wouldn’t worry too much if the above presentation is a little too jargon-laden for your taste. As I can make out from the information available, this new monoclonal has the potential for better ADCC (effector cells such as neutrophils, macrophages, NK cells, etc. needed to do the cell kill, once the target B-cell has been tagged by AME-133), but not any better than Rituxan when it comes to CDC (complement dependent cytotoxicity). CDC is the one area where HuMax-CD20 seems to excel. It will be interesting to see how these various new anti-CD20 monoclonals play out in the real world of treating patients.

Bottom line: good things are happening folks! Better monoclonals are in the pipeline, fully humanized and engineered to make better use of the multiple pathways of targeted cell kill. These are no longer just blue sky dreams or wishful thinking. These drugs are past lab / mice studies and making it into human trials, some of them in late stage trials like the HuMax-CD20. I am rooting for the day when our guys can get clean CRs with little or no minimum residual disease, using low toxicity drugs that do not screw up their immune systems in the process.

Be well,

Chaya
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