Today was exciting. A great little company got bought out (see today’s news release) and we all got very pumped up about Immunotherapy for cancer treatment. If you saw our AML series (below) you’ll know why new therapies are desperately needed.
Last year at ASCO was very exciting, as immunotherapy was showing great promise across tumor types, but especially in melanoma. The buzz was amazing. But there was also a funny undercurrent.
The ads placed in the daily news bulletin from the American Society of Clinical Oncology (ASCO) meeting last year in Chicago were striking. They came in two distinct formats. One set, aimed squarely at MDs, came loaded with technical information, focused on progression free survival (PFS) and overall survival (OS) data. Lets keep in mind that for advanced solid tumors, such numbers can be small: a few months, maybe a year. Indeed much of the buzz at that meeting came from immunotherapy clinical trial results. It became clear that a small number of patients in immunotherapy clinical trials were living long enough to create a long “tail” on the mortality graphs. Ribas et al. (http://clincancerres.aacrjournals.org/content/18/2/336.long) illustrated the concept in 2012:
Targeted therapies (small molecule drugs, chemo, radiation) are illustrated, schematically, on the right. The is a futility inherent in that graph. Immunotherapeutics are illustrated on the left. Again, this is not real data, just a thought cartoon.
The long tail phenomena suggests that Immunotherapy is an example of drug development that has the potential to be transformative, to utterly alter cancer patient care. CAR-T technology may be another. Real examples of successful transformative therapies include the TNF antagonists in the treatment of RA. The use of beta interferons (and many other drugs) to treat MS, and CD20 antibodies to treat B cell lymphomas are other good examples. Getting there in advanced solid tumor treatment will take some time. And 10% of patients living a long time can also move the OS number a bit, even though most patients are not benefitting. Regardless, this is a big step, as it suggests that one could work to increase the “height” of that tail, to 20, 30, 40% and so on. That’s a great goal.
We’re not there yet for most solid tumors. This brings us to the second ad style that featured prominently in the pages of the ASCO daily bulletin. These ads were still loaded with technical information, in the small print, but were presented in an emotional manner. These ads were aimed at patients, or perhaps at the way oncologists think about their patients. In these ads well-groomed 60ish looking couples sat smiling at sunsets or grazing lovingly at each other. “Its not just another Sunday, it’s another Sunday!” said one. It might as well have been a Cialis ad.
There is nothing wrong with this, except perhaps demographically, as the ads featured mostly white models, but even then I think this reflects the demographics of oncologists more than patients. But it should make us think a little bit about the ephemeral nature of most of the progress being made – a few more months as a new drug works, only to be undermined by the next set of treatment resistant mutations. Many new drugs are not transformative, they are incremental. We should also remember that when talk about the promise of combination therapies we often forget that many of the combination agents are very hard to take, especially for older patients. For many patients, another Sunday is another day of struggle against brutal disease and harsh treatments. Obviously, we want to do better.
On a positive note, I remind myself that when I look at new clinical trial data I am almost always seeing data on patients who are out of options, having failed standard of care. There is a lot of argument about clinical trial design in these settings. One good question is whether the FDA should allow investigational drugs to be given to cancer patients earlier – this sounds great until something doesn’t work or makes things worse. As a result it takes time for newly developed drugs to move from third line to second line to front line therapy.
We spend a lot of time tracking clinical trial information and data for signs of “actionable” data. Actionable may mean that a biopharma client advances or kills a program or an investment client executes a trade. Both of these examples reflect the reality that drug development creates a very difficult competitive landscape, requiring years of investment and endless effort. At the end of the day, if all goes right, the patient, the investor, and the drug development industry all win. That’s why we’ll be back at ASCO, AACR and ASH. It’s also why we track other difficult diseases, like lupus, fibrosis, diabetes and COPD, to name a few. And of course it’s why we start new companies. We want to find those drugs that will make the patient’s next Sunday pretty much like every other Sunday – transformative therapies. Drugs that are transformative in such diseases will be few, and special. We want to be there when they debut.