So it may be that the doyen of American drug companies when I entered the business may be falling into a death spiral. Merck’s withdrawal of Vioxx from the market combined with its major statin Zocor going off patent in 2006 may relegate it to the second tier of international pharmas, falling well behind Pfizer, GSK and the new Aventis/Sanofi. The new Aventis/Sanofi combo has its anti-smoking anti-fat pill Acomplia coming out in a couple of years, which may end up being the biggest selling Rx product of all time.

Merck’s Vioxx had certainly had its problems. Today’s New York Times article details the very recent history of Vioxx. As THCB noted back in August, a Kaiser study suggested that there were instances of heart attack and stroke among Vioxx patients, though not for Pfizer’s Celebrex. Once Merck’s own clinical study (which was trying to extend the indication to stomach polyps) showed the same thing, the company in consult with the FDA and no doubt its legal staff and investment bankers decided to take the enormous step and bite the bullet.

Not since the withdrawal of Baycol has there been such as tizzy in big pharma land, and Vioxx was not a 5th in class drug like Baycol. However, the Cox-2’s are a interesting case where a drug that has a benefit for some patients was probably being used too widely anyway. The Cox-2s are no more effective at reducing pain but were introduced and marketed as being better for those 30-40% of NSAID and ibuprofen users who had stomach pain. Express Scripts has shown in its studies that many if not most of those using Cox-2s were not suffering that stomach pain in advance and should have been on a cheaper drug first. Another Expresss Scripts study showed that over half of older Cox-2 patients were taking aspirin anyway, which meant that they were still probably getting the pain relief and also stomach problems of aspirin, probably negating the value of the Cox-2 in the first place–if the Cox-2’s even worked for those stomach problems in the first place (and there’s some evidence that Celebrex doesn’t). As a PBM, Express Scripts of course wants its customers to take OTC ibuprofen and an OTC PPI for their associated stomach problems. And of course there are plenty of alternatives beyond the aspiring/PPI combination. Even the NY Times Editorial page weighs in on overuse of Cox-2s. All this of course will make the already delayed FDA approval of Merck’s delayed replacement for Vioxx, Arcoxia, and Prexige from Novartis, much trickier.

Longer term this is all very grim for Merck. Below (purloined from the Times and IMS) is a list of 2003’s top Rx sellers (by $$) in the US. Note that Merck has only Zocor, Fosamax and Vioxx on the list. (The list says that it has Nexium too, but of course that’s Astra-Zeneca’s).

1. Lipitor, $6.8 billion, cholesterol,Pfizer Inc
2. Zocor, $4.4 billion, cholesterol, Merck & Co.
3. Prevacid, $4.0 billion, heartburn, TAP Pharmaceutical Products Inc.
4. Procrit, $3.3 billion, anemia, Johnson & Johnson
5. Zyprexa, $3.2 billion, mental illness, Eli Lilly & Co.
6. Epogen, $3.1 billion, anemia, Amgen Inc
7. Nexium, $3.1 billion, heartburn, Merck & Co.
8. Zoloft, $2.9 billion, depression, Pfizer Inc.
9. Celebrex, $2.6 billion, arthritis, Pfizer Inc.
10. Neurontin, $2.4 billion, epilepsy, Pfizer Inc.
11. Advair Diskus, $2.3 billion, asthma,GlaxoSmithKline PLC
12. Plavix, $2.2 billion, blood clots,Bristol-Myers Squibb Co.
13. Norvasc, $2.2 billion, high blood pressure, Pfizer Inc.
14. Effexor XR, $2.1 billion, depression, Wyeth
15. Pravachol, $2.0 billion, cholesterol, Bristol-Myers Squibb Co.
16. Risperdal, $2.0 billion, mental illness, Johnson & Johnson
17. Oxycontin, $1.9 billion, pain, Perdue Pharma
18. Fosamax, $1.8 billion, osteoporosis, Merck & Co.
19. Protonix, $1.8 billion, gastrointestinal reflux disease, Wyeth
20. Vioxx, $1.8 billion, arthritis, Merck & Co.

So soon they’ll only have Fosamax on the list. Forbes has a hard hitting article suggesting that both the CEO Gilmartin’s days are numbered and that Merck itself will become a takeover target. For a company that was the leading pharma company in the world in the early to mid-1990s, that would be a mighty fall.

Of course, if this can happen in as big a market in Cox-2s, can it be long before there’s more analysis of the biggest market of all, the statins, to see if any share Baycol and now Vioxx’s fate? There are already (as reported by Medpundit) some dissident physicians questioning their value.