ASCO: Too Many Inhibitors?

There are still a few things to talk about from the ASCO conference, but I saw an article this morning that I found really interesting. It basically says something that I have been wondering about for a couple of years -- are there too many inhibitors out there? Do we really need any more?

The article is called "Post-ASCO News Alert: Mei Pharma’s Phase II zandelisib in r/r follicular lymphoma draws expert pause on clinical value; side-effect edge doubtful," and it was posted today in Clinical Trial Arena. It isn't really reporting on research so much as questioning why the research is happening.

The article features some lymphoma experts discussing the results of clinical trials for Zandelisib. There were three presentations at ASCO this year that discussed results of Zandelisib. The results were good. But the question is, according to the article, are the better -- more effective or safer than the four other PI3K inhibitors that have already been approved for use on Relapsed or Refractory Follicular Lymphoma. Those are Idelalisib, approved by the FDA in 2014, Copanlisib in 2017, Duvelisib in 2018, and Umbralisib in February 2021.

The reason that four of the same kind of treatment have already been approved is because they are all slightly different. While they all inhibit the same process that is necessary for a cancer cell to survive, there are actually a few different variations of that process, because there are a few different variations of one of the proteins involved. They are the same in many ways, but different in some ways, too. 

So far, from what I can tell, the differences don't seem to make all that much of a difference. In other words, there isn't one inhibitor that whose difference makes it stand out all that much from the others. I'm sure the makers of the different inhibitors would disagree, but I don't see any consensus on one being "the best."

And that's the issue with Zandelisib. Is there enough evidence from trials to show that it will be more effective, or safer, than the other options already available? Those experts in the article don't seem to think so.

It's a tough situation for a pharma company, I'm sure. If they've already spent millions developing a treatment, they'll probably want to see it approved so they can make some sales and make back some of that money. Or maybe they think their treatment can help some people that otherwise wouldn't be helped. (If you're cynical, you might not believe that last one, but the people I have met who work for pharma companies do seem genuinely interested in helping others.)

The problem, though, with having so many treatments that do the same thing, without being hugely different from one another, is that it creates confusion for patients, who have too many choices (and maybe for some doctors, too). Worse, in my opinion, is that all of the money that went into developing a treatment that duplicates other treatments could have gone to developing some new approach.

But that's hard to know from the start. I've been a grant reader for cancer research (more on that soon!), and seeing a scientist describe early research is exciting. There's lots of hope and promise that this research project might be The One. And maybe it isn't until much later in the process when it becomes clear that The One is really just Another One. Still helpful to some people. Just not what everyone was hoping for. 

So I found the article interesting at first because it expressed my frustration -- there seems to be a lot of duplication in cancer treatment. Lots of inhibitors, lots of Rituxan biosimilars, etc. But then, as I thought more about it, it reminded me of how difficult it must be to try to create a new treatment, especially when you know that a bunch of other people are working on a similar project, and might do it faster than you. But it also makes me appreciate that we do have choices, and in the end, that's a good thing.

Looking at all of the presentations at ASCO on Follicular Lymphoma, it's still exciting to think that one of them might be The One some day. Here's hoping that some new treatment still in development gets to patients soon, and dies the job better and safer (and maybe longer) than everyone else.