John LaMattina: Why was bapineuzamab moved into Phase III trials?
pharmafile | September 24, 2012 | Feature | Business Services, Manufacturing and Production, Medical Communications, Research and Development, Sales and Marketing | AD, John LaMattina, Pfizer, bapineuzamab
The recent news that the Pfizer/J&J Alzheimer’s Disease drug, bapineuzumab (bapi), had failed in critical clinical trials resulted in great disappointment in the AD community.
For those impacted with Alzheimer’s, patients and their loved ones, this was yet another blow in that a potential remedy was now gone. For scientists involved in seeking a cure for the disease, this was yet another failure.
The failure of bapi also resulted in further questions about the validity of the amyloid hypothesis – that the disease is caused by the deposit of amyloid plaques in the brain thereby causing the erosion of mental acuity.
But I was not prepared for the broad criticism of the companies that took the chance to advance bapi into late-stage development. These critiques have some justification. When the mid-stage clinical results (Phase II) were disclosed by Wyeth (before the Pfizer acquisition), the efficacy signal was mixed. The data indicated that there might be some improvement in a certain type of Alzheimer’s patients, but in some patients the drug didn’t work at all.
This type of result is a nightmare for a pharmaceutical company. Usually, the Phase II results drive momentum and enthusiasm for the programme. In a case like this, where Phase II is not conclusive, the decision becomes agonising.
While I had no part in the bapi discussions, I have been a part of such discussions over the years, and they go something like this. Major meetings will occur in the company which brings together scientists (both internal and external), clinical disease experts and the marketing team assigned to the programme.
These folks are grilled about the data by upper management and all aspects of the programme (trial design, data analysis, adverse events, etc.) are reviewed. From experience, I can tell you that such discussions can be very intense.
There is good reason for this. The investment the company makes in committing to Phase III is considerable. I believe the reports that the bapi Phase III programme cost over $400 million are accurate. One decision that could have been made would have been to carry out more Phase II studies in the hope of generating additional data to illuminate the decision.
In hindsight, this might have been a good move. However, often additional studies are not definitive and you are back to where you were originally. Sometimes, the best thing to do is to bite the bullet and plunge into the Phase III programme.
There are those who felt that the decision to move bapi into Phase III was driven by a hope that Wyeth/J&J could be lucky, the studies could work and then they would have a blockbuster.
Actually, in some ways, the decision to discontinue a Phase II drug at this stage is easier. I suspect Wyeth/J&J knew that bapi had less than a 50-50 chance to succeed. Why risk $400 million along with the ignominy of a potential major Phase III failure? Perhaps the answer lies the fact that there were groups of stakeholders who desperately wanted bapi to advance.
Alzheimer’s disease patient advocacy groups would top the list. These people, who are doing their utmost to help find any treatment for this disease, would have been outraged had bapi been dropped at Phase II. Furthermore, their concerns would have been supported by leading experts in the field.
Back in 2008, many leading experts in Alzheimer’s strongly believed in the science behind bapi and they would have been quite negative about ending the programme. Finally, dropping bapi would have caused public relations damage. Imagine the headlines: “Big Rich Pharma Companies Dump Promising Drug For Alzheimer’s. Patients, Scientists Crushed.”
Now, you don’t make major commitments of resources based on opinions of patient advocacy groups or external scientific leaders. However, this was a situation where these companies were in possession of a relatively safe drug, with a modest chance of success in being efficacious in what may be the biggest scourge that society will face. How can you not make this investment?
Interestingly, another similar situation exists in Merck cardiovascular research. Merck’s CETP inhibitor, anacetrapib, was advanced into Phase III last year. This is a controversial area of research because while the drug has a promising profile in that it both raises good cholesterol and lowers bad cholesterol, Pfizer’s CETP inhibitor, torcetrapib failed in trials. This is another case where the medical need for a new therapy is considerable, however, the cost of the Phase III programme is around a half a billion dollars.
I’m told that there was considerable debate inside Merck whether to advance anacetrapib into Phase III or not. If this programme fails, there will be a reaction similar to that around the Wyeth/J&J bapi situation.
But, then again, anacetrapib may be shown to reduce heart attacks and strokes. That’s what pharmaceutical R&D is all about. It is a high risk, high reward business.
However, when a novel drug is shown to work, everyone wins – especially the patients.
John LaMattina is the former head of R&D at Pfizer. His latest blog posting can be read on the Forbes site.
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