‘ILLUMINATE’ Trial fails to illuminate Pfizer’s hopes

The most unexpected has happened !!!! Pfizer announces the termination of ‘ILLUMINATE’ clinical trial for drug Torcetrapib after disappointing adverse events. This is a huge blow to Pfizer’s plans of continuing the monopoly in Lipid lowering drugs.

As you know ‘Torcetrapib’ had generated considerable interest because of its unique mechanism of action. This inhibits ‘cholesteryl ester transfer protein (CETP)’ and thereby raises the HDL Cholesterol (Good Cholesterol) unlike statins, which act by lowering the LDL Cholesterol (Bad Cholesterol). If the hypothesis works practically, a combination of Torcetrapib & Atorvastatin could have been a wonderful solution in dyslipidemia.

I’m personally disappointed. I was excited about this new molecule in the recent past. The initial trial results were positive and enthusiastic. I was looking forward for this drug in markets. Nevertheless, I am happy that Pfizer took this painful decision at the correct time, thus preventing another drug going ‘Vioxx’ way. I mourn the deaths of clinical trial participants who died prematurely by participating in this trial.

According to the reports, Pfizer was conducting a test of 15,000 patients, half of whom took the drug combination. The rest took Lipitor alone. Eighty-two of the patients taking the combination died, while 51 died taking just Lipitor. Few weeks back, Pfizer had admitted that Phase III study indicated patients using the torcetrapib/atorvastatin combination experienced slightly higher systolic blood pressure than those who took Atorvastatin alone. There were doubts surrounding the issue but repeated assurances from Pfizer’s CEO had given hopes to Investors till this Saturday.

Torcetrapib had its share of critics & debate surrounding it. It was pipped as the "one of the most important developments in our generation", It was compared to a panacea for CVS risk factors. There was another interesting debate in NEJM about “Should Marketing Drive the Research Agenda?” by Jerry Avorn.

For Pfizer, this is an absolute disaster. High hopes of finding a successor to the Lipitor gone for a toss. Pfizer was expecting to get it in market before the expiry of Lipitor’s patent. That is before 2011. By introducing a combination, Pfizer had a clear chance of dominating the arena and withstand the competition from generics. Pulling off from Phase 3 trials translates to huge losses amounting to several hundred million dollars.

I believe in the $7 billion a year strong R&D of Pfizer. Hopefully, they will work on some lead sooner and fill the gap going to be created by Lipitor’s patent expiry. Leaving a $13.5 billion a year drug for the generic market brings lot of heartburn.

Pfizer has two more CETP inhibitors in development and so do some other Pharmaceuticals like Merck, Roche. Now those development exercises warrant for extra caution.

Having no promising candidates in pipeline, the likely move of Pfizer will be acquisitions. This shopping spree may result in collaborations are buying out of smaller drug discovery firms. Even several bio-tech firms in India has shown promise and are working on different leads. Let us wait & watch for…. “Where will Pfizer go for shopping?”

At the end, this saga shows how difficult, painstaking and expensive is this whole business of drug development. The feeling when you pull out from Phase 3 trials will be the same as the feeling of a mother who has just given birth to a stillborn baby after 9 months.

What a disappointment !!!



  1. qshandy says

    any thoughts on drugs acting as CETP enhancer? (probucol)