Pfizer’s latest major pipeline clear-out resulted in losses of Sutent development in a number of cancers and figitumumab in non-small cell lung cancer, among many other discontinuations.

As of the firm's Sept. 27 pipeline update, Pfizer had 118 programs in development and registration, down by 31 programs from January, when it issued its previous update. Pfizer said it will be looking to out-license a small number of the discontinued programs (see chart for cancelled programs).

Of the 118 programs now in its pipeline, 26 are in Phase III, and nine are in registration phases. Twenty-seven of the total, or 23%, are biologics, the company reported. Out of Pfizer’s 26 late-stage candidates, 14 are novel, while the rest are marketed drugs being tested for expanded indications.

Pfizer continues to focus its R&D on ten major therapeutic areas, including cardiovascular/metabolic, neuroscience, oncology, inflammation and pain – the same categories it staked out when it revamped its priorities in early 2008 (Also see "Pfizer Plots Major Phase III Push" - Pink Sheet, 5 March, 2008.).

Analysts shrugged off the update, noting that it offered few surprises. Still, it was "notable for the number of late-stage discontinuations,” wrote Barclays analyst Anthony Butler in a Sept. 28 note.

In a Sept. 27 note, UBS analyst Marc Goodman described the pipeline changes as "minor.” The "decrease in the number of programs is a positive sign that management is proactively restructuring the pipeline by selecting the best programs to move forward and cutting appropriate programs to cut R&D costs,” Goodman observed.

Pfizer's patent cliff deepens in 2012, when its best-selling cholesterol drug Lipitor (atorvastatin) loses exclusivity in the U.S., putting it under intense pressure to develop promising candidates that can make up some of the revenue gap. In its last earnings release in August, the company maintained revenue targets of $65.2 billion to $65.7 billion for 2012 and said it was on track for spending cuts of $4 billion to $5 billion by the end of 2012 (Also see "Pfizer's Focus Is On "Bolt-On" Acquisitions After Wyeth Merger" - Pink Sheet, 3 August, 2010.).

The company has committed significant R&D resources to building its presence in oncology, but the revisions offer clues that the direction of its oncology program is struggling in the wake of several setbacks.

Pfizer had been looking to expand sales of its blockbuster Sutent (sunitinib), which is approved in advanced/metastatic renal cell carcinoma and gastrointestinal stromal tumors. But the drug has disappointed outside its core approved indications, with poor showings in breast, lung and other cancers (Also see "Pfizer Seeks To Salvage Sutent For Lung Cancer" - Pink Sheet, 24 August, 2010.).

As part of its pipeline update, Pfizer announced it was dropping development of Sutent in hepatocellular, breast, lung and prostate cancer. The company had also reported on Sept. 27 that sunitinib failed to show an overall survival benefit in a Phase III trial in prostate cancer, according to an interim analysis by a data monitoring committee. Sutent remains in late-stage development for adjuvant treatment of renal cell carcinoma.

Figitumumab’s limitations also became clearer early this year, following the release of disappointing data in non-small cell lung cancer ([A#1216099165884]).

Another hole in the oncology pipeline comes from the Phase II CDX-110 vaccine for brain cancer. Pfizer announced recently that it was ending a deal for development of the vaccine with developer Celldex ("Pfizer Axes Deal For Brain Cancer Vaccine, Leaves Partner Celldex in the Lurch,” "The Pink Sheet” DAILY, Sept. 3, 2010).

"We believe apixaban and tasocitinib may be the only remaining late-stage candidates to hold billion-plus peak sale potential,” Barclays' Butler says.

Oncology is still a high-priority research area for the company, a spokesperson confirmed. More than 20 biologics and small molecules are in development. And the company is currently running more than 100 clinical trials in oncology, including studies in some of the most prevalent and difficult-to-treat cancers, such as lung, renal cell and hematologic malignancies, the spokesperson pointed out.

Heat Is On Apixaban And Tasocitinib

The disappointments aren't limited to oncology. Among the non-cancer candidates in advanced development are tanezumab and dimebon, which "don’t have a lot of probability of progressing,” Butler noted. The company said in July it was suspending Phase II trials of tanezumab for lower back pain and diabetic peripheral neuropathy in light of results from osteoarthritis trials.

The losses this year put enormous pressure to achieve on certain key candidates, including the novel oral anticoagulant apixaban and the JAK inhibitor tasocitinib for rheumatoid arthritis.

"We believe apixaban and tasocitinib may be the only remaining late-stage candidates to hold billion-plus peak sale potential,” Butler said.

The market for new anticoagulants is said to be worth some $10 billion. Apixaban’s safety profile looked promising in a recent study against aspirin, and results due in 2011 testing the drug against warfarin are eagerly awaited (Also see "Apixaban Impresses At ESC, Leading To Speculation About An Early Filing" - Pink Sheet, 31 August, 2010.).

As for tasocitinib, Pfizer is set to present positive results from the open-label Phase II 1024 study at the upcoming American College of Rheumatology meeting in November.

Based on ACR abstracts, the oral RA drug "continues to show impressive safety and efficacy at two years,” commented Leerink Swann analyst Seamus Fernandez in a Sept. 29 note. Results from the 1045 Phase III study may also be released at the meeting as a late-breaking abstract and are expected to be positive.

"Based on the data and improving feedback from rheumatology thought leaders, we are increasingly convinced that tasocitinib will achieve blockbuster status and compete with injectable RA therapies over time,” the analyst wrote.

Mikael Dolsten, Pfizer's head of worldwide R&D, was not available for an interview to discuss the pipeline. During a Morgan Stanley presentation on Sept. 13, however, Dolsten, who formerly headed R&D at Wyeth, commented that in early studies the drug appeared to be on par with biologicals and yet offers the convenience of an oral pill.

"Obviously, we would be extremely proud to move that drug to the market as the first oral drug in a decade to be a meaningful drug for patients with rheumatoid arthritis and with potential for many other inflammatory diseases,” he said.

Oncology Drugs Work With Precision

In his Morgan Stanley presentation, Dolsten also highlighted the potential for targeted drugs like crizotinib in oncology. Results of a Phase I trial of the ALK inhibitor in a subset of NSCLC patients were featured prominently during the plenary session at the American Society of Clinical Oncology meeting in June (Also see "Crizotinib Holds Promise For Lung Cancer, And For Pfizer Oncology" - Pink Sheet, 14 June, 2010.).

Based on the results, the company has sped up development, moving straight into Phase III. Not only is crizotinib an exciting drug, but it also illustrates the potential for "precision medicine,” Dolsten commented.

In terms of the company’s early- to mid-stage pipeline, Dolsten highlighted five areas of development progressing to proof-of-concept that "show what the new Pfizer is putting its investment behind and what could refuel its Phase III program.”

Diabetes candidates will help refuel Pfizer’s Phase III pipeline, said Mikael Dolsten, president of worldwide R&D.

Diabetes – historically not the biggest area of focus for Pfizer – was at the top of the list. In particular, the company is developing long-acting GLP-1 proteins, based on technology from CovX, which it acquired in late 2007 (Also see "Pfizer To Fold CovX Into Bioinnovation Unit" - Pink Sheet, 18 December, 2007.). The GLP-1 class is expected to take a sizeable share of the ever-growing worldwide diabetes market.

CovX developed a technology platform linking therapeutic peptides to an antibody scaffold. Pfizer is considering development of GLP-1 candidates based on this scaffold platform with dosing once a week and once every two weeks.

The company is also nearing proof-of-concept with a candidate in the new class of SGLT-2 inhibitors for diabetes (Also see "Big Pharma Tries Out New Class On The Diabetes Block: SGLT-2" - Pink Sheet, 1 July, 2009.). Dolsten noted that the SGLT-2 candidate seems to provide "very powerful glucose control” with no weight gain.

The second area of promise for refueling the Phase III pipeline is a Phase II glucococortid receptor agonist for rheumatoid arthritis. Pfizer now has clinical data showing its benefits for relieving symptoms with important advantages over steroids, including minimal risks to bone.

"We have created a completely new chemical scaffold that hits the same receptor as prednisone but shows much better tolerability,” Dolsten said.

In vaccines, the company has proof-of-concept data for a meningococcal serogroup B vaccine for adolescents and the company is preparing to start Phase III studies early next year.

As for up-and-coming cancer candidates, data for the antibody drug conjugate inotuzumab, which links a CD22 antibody to rituximab, suggest a strong response for advanced refractory diffuse B-cell lymphoma.

Dolsten also chose to highlight a promising early-in-development candidate for high cholesterol. The gene proprotein convertase subtilisin/kexin type 9 (PCSK9) has been linked to LDL cholesterol and heart disease.

Pfizer has a monoclonal antibody against this genetic target in Phase I and results so far show "rapid, profound cholesterol-lowering effects beyond what we have ever seen before and with good tolerability,” Dolsten told analysts.

Dolsten concluded that the projects he highlighted provide just a glimpse of what the company has in its pipeline: "Of course these are still early clinical studies and different data might emerge. But it certainly looks like very exciting opportunities here.”

By Emily Hayes

Pfizer Clears Out Pipeline: After Oncology Disappointments, Talks Up Diabetes

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