I discussed pretty extensively in a post last November the fact that I expected to see sales of Genentech’s (ticker: DNA) Avastin explode in light of the fact that it had been approved for NSCLC at a dose of 15 mg/kg, three times the previously-approved dose of 5 mg/kg for colorectal cancer.
In the meantime, I’ve been seeing some limited usage of Avastin for yet another huge market, and the one which gets a disproportionate amount of publicity- breast cancer. In some studies, high-dose Avastin (15 mg/kg and even higher) has sometimes appeared to improve outcomes in some cases.
But the usage of high-dose Avastin does not seem to be taking off, even with FDA approval, and the matter deserves a little deeper investigation.
At first blush, the high-dose approval would appear to be screaming-good news for Genentech. However (and this is a BIG however), what’s not being publicized quite so well is that, possibly because of Avastin’s anti-angiogenesis mechanism of action, the high doses seem to have a noticeable incidence of very serious GI side effects, particularly ulcers and perforations, sometimes life-threatening.
Anti-angiogenesis is great when it comes to attacking tumors. Prevent the formation of new blood vessels, choke off their blood supply, they die. Wonderful. And it “doesn’t attack healthy cells the way ‘traditional’ chemo does”, an implication that this is some kind of magic bullet.
It’s not. To say “it doesn’t attack healthy cells the way traditional chemo does” is a qualified statement, but the marketing people won’t mind at all (wink) if you and maybe a few hundred thousand healthcare professionals (wink) misinterpret that as “it doesn’t attack healthy cells.”
A Little Drug-Marketing Background from an Insider
This type of thing is not unique. It’s not even uncommon. It’s one of the most effective marketing techniques drug companies use, and they use it extensively. Aventis developed the market for one of the most successful drugs in history, Lovenox, by emphasizing the tagline that it “didn’t need to be monitored like regular Heparin.” [a clearer statment would have been “the very possible risk of bleeding complications with Lovenox cannot be reliably predicted with the clotting tests performed on unfractionated heparin”- I think you can see the difference in connotation by the wording they used] Healthcare in general dropped the last three words from Aventis’ tagline (like anyone, we simplify and remember the short version), misinterpreted it in exactly the way they were supposed to, and to this day we have many, many (many) physicians who mis-dose Lovenox, particularly in patients with renal dysfunction, because they think “Lovenox is safe,” and “Lovenox doesn’t have to be monitored,” and (contrary to Aventis’ official recommendation), “Lovenox doses don’t have to be adjusted.” The campaign to educate them otherwise has been amazingly weak and ineffective (wink).
A much more recent and public example has been the marginally-effective HPV vaccine developed by Merck, which whenever discussed in public was discussed with the misnomer “Cancer Vaccine,” not by accident, and the media did the rest. Well, the media and some good Friends of Merck who happen to hold high political positions and command a lot of attention. As a healthcare professional, this angered me, but I’ve seen it before. As a father of three daughters, it outrages me to this day, which is why I haven’t discussed it much publicly. I might lose my temper. This is NOT a miracle drug and this will NOT eradicate cervical cancer, and the science says as much, but it’s not science that gets the headlines- it’s the marketing jargon.
And Amgen’s drug Vectibix, which the “anal-ists” were proclaiming to be the next blockbuster? It has a documented incidence of potentially-severe side effects of… and this is not a misprint… approximately 90 percent. Not 0.9%, not even 9% (which would be very notable). If you bet your life savings on Amgen, do it because of their marketing prowess and political power, not because of this drug.
What Does This Say About Avastin?
Back to Avastin. I would also point out that anti-angiogenesis is not synonymous with “good” in most realms other than tumor destruction. In fact, various drugs and viral vectors (yes, volunteers being infected with a strain of Herpes on purpose) have been studied for many years now in an attempt to promote angiogenesis in heart patients, which might lengthen their survival, improve their life, etc by providing increased blood flow to the heart via newly-grown coronary blood vessels.
This gets to the overall point that drug companies universally do not publicize: a drug’s beneficial effect is because of how it works, and very often a drug’s detrimental side effects are, guess what, because of how it works. COX-2 inhibitors (the entire “Vioxx” class) are great for arthritis pain, because they inhibit COX-2. They aren’t so great for the heart, because they inhibit COX-2!
Avastin at very high doses seems to be doing “something” which leads to an increased incidence of GI tissue necrosis, damage and perforation. GI tissue is highly-vascularized, which means it’s continually growing millions of new blood vessels to support the tissue turnover and proliferation. In other words, GI tissue is big on angiogenesis. I haven’t seen any published studies which definitively show why Avastin has the detrimental effects it does (such studies are -wink- very difficult to find funding for), but there appears to be a potential connection here, IMHO.
The upshot? Avastin’s high-dose use in NSCLC isn’t rocketing skyward as was expected, and the potential new use in breast cancer may be questionable.
That’s my version of fudamental analysis. You… (hey, are you still listening?)… you keep an eye on that darned chart and watch those stops!
