Pfizer views its planned filing for its investigational HDL/LDL cholesterol combination therapy torcetrapib/ Lipitor as the initiation of a dialogue between the company and FDA, not necessarily the start of a standard review.

"Our purpose in filing is to get these data in front of the FDA - to get their view on the imaging studies and the relationship to progression/regression of atherosclerosis," Pfizer Global Research & Development President John LaMattina said during the company's third quarter earnings call Oct. 19.

"We have said all along that approval on imaging is not a guarantee, but we have to file in order to be able to start the dialogue and get the conversation on this thing going."

Pfizer hopes to base its HDL-elevation efficacy claims for the torcetrapib/Lipitor(atorvastatin) combination therapy on intravascular ultrasound (IVUS) data (¹ [A#00680030008], p. 14).

The company plans to file an NDA for torcetrapib/ atorvastatin in late 2007 based on the imaging data.

LaMattina acknowledged that the "filing does not...anticipate a one-year approval for this compound because the FDA has never agreed to approval on imaging alone."

"FDA has made it very clear that they are not bound to approval on imaging alone and are interested as well in the morbidity and mortality studies, which won't be out until late 2009."

Pfizer said it is not including torcetrapib/Lipitor sales in its revenue guidance for 2009; the firm is embarking on a comprehensive cost-cutting initiative in the face of expected flat revenue through 2008 (see ² Also see "Pfizer Cost-Cutting: Details Are Sketchy, But Sales Force Is On The Table" - Pink Sheet, 23 October, 2006.).

The exec attempted to explain the unique nature of preparing a filing with little knowledge of FDA's approval criteria.

"You are filing an NDA, but not necessarily in a situation like you may have an NDA for oncology where you have a clear result that the FDA has agreed to already," he said. "We are really doing, for lack of a better term, a major biological experiment here where the outcome could have all sorts of parameters."

"Two of the three studies could be wildly positive and one could be neutral," he said. "If I was in the FDA's position, I would take the same view - until you see the data...it is hard to make a commitment as to what would be approved for what."

FDA has said that whether regression of arterial plaque will be viewed as a surrogate for cardiovascular outcomes remains an open question (³ Also see "Cardio Markers Useful For Selecting Responders, Not As Outcomes Surrogates" - Pink Sheet, 17 April, 2006., p. 17).

Pfizer Chief Medical Officer Joe Feczko said that the imaging studies, which compare torcetrapib/Lipitor with atorvastatin alone will likely not provide useful outcomes data.

"We have got a pretty tough comparator there so the only way to get any kind of reasonable fix on the endpoints that are morbidity and mortality - we would need to have a trial that had about 15,000 patients enrolled," he said.

Data from the imaging studies will be unveiled at the American College of Cardiology annual meeting in March. LaMattina said that until that time, the results are "going to be kept in strict secrecy, including from most Pfizer colleagues. That is the agreement that we have with Dr. [Steven Nissen (Cleveland Clinic)] on IVUS as well as the other studies."

While the firm does not expect to release results from the trials in advance of the meeting, "if there was [a] negative safety signal, that might be something to go public on," LaMattina said.

Although torcetrapib has been developed as a fixed-dose combination with Lipitor, LaMattina said Pfizer is also considering developing the cholesteryl-ester transfer protein inhibitor as a monotherapy, something the firm has previously suggested it would not do.

Pfizer hopes that torcetrapib will be the cornerstone of the company's CETP inhibitor franchise.

"What's really important to understand is that we think of this as a CETP franchise....We believe that this mechanism of action makes a lot of sense and we are investing in it," Pfizer CEO Jeffrey Kindler said.

- Mary Bruce

Pfizer Torcetrapib Filing To Start ‘Dialogue,’ Not Necessarily Standard Review

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