At Pfizer, Even the Biggest Biosciences Company Finds Room to Grow in Oncology

Denise Bruns, PhD

When it comes to market capital, Pfizer, Inc. tops a list of major companies in the biosciences market. Following its acquisition of Wyeth Pharmaceuticals in 2009, Pfizer now has 14 blockbuster drugs, or drugs that generate at least $1 billion each in annual revenue for the company.

Despite a wide range of products that cover a number of diseases and ailments, the company’s oncology division is still finding new ways to meet unmet needs for cancer patients. In fact, several products in the company’s pipeline are Pfizer’s first forays into certain tumor types.

Pfizer currently has 18 new molecular entities in various stages of clinical trials, and 2 of them—crizotinib for non—small cell lung cancer (NSCLC) and axitinib for advanced renal cell carcinoma (RCC)—have been registered with the FDA. In addition, 5 of those compounds are in clinical trials for diseases outside of their primary indication.

“If you look at our oncology portfolio about 3 years ago, we had sunitinib and not much else,” said Denise Bruns, PhD, late-phase development group leader in clinical development and medical affairs at Pfizer. “Today, we have a lot more phase III clinical trials, especially after the addition of the Wyeth portfolio.”

“

Our oncology division is determined to find which of these therapeutic agents are most likely to benefit the patients. ”

—Denise Bruns, PhD

Bruns said that, going forward, part of the oncology division’s plan is to try and steer clear from all-cancer treatments and focus on those that have known genetic markers, thereby allowing the creation of more targeted therapies for more specific tumor types.

For example, inotuzumab ozogamicin, a humanized monoclonal antibody for the CD22 molecule, is currently in a phase III trial for treating aggressive non-Hodgkin lymphoma. A phase II trial is also underway to see if inotuzumab can be used for treating indolent non-Hodgkin lymphoma. Bruns said inotuzumab and the recently approved crizotinib, which will be marketed by Pfizer as Xalkori, are 2 of the first drugs that the company has developed for the treatment of blood cancer.

“Our goal is to become the new standard of care and be able to go against [Roche’s] Tarceva,” Bruns said. Despite a more focused approach, it doesn’t necessarily mean that some of the therapeutic agents under development will be limited to 1 tumor type. In June, axitinib, a vascular endothelial growth factor receptor tyrosine kinase inhibitor, was accepted for review by the FDA for the treatment of advanced RCC based on the results of phase III clinical trial data. Axitinib is also currently in a phase III trial to test its efficacy in treatment-naïve advanced RCC patients, as well as a phase II clinical trial to determine if it can be used to treat patients with lung cancer or thyroid cancer.

Table. Pfizer's Phase II/III Oncology Drug Pipeline

Drug Name/Compound

Mechanism of Action

Indication(s)

Phase

Sunitinib malate

Multiple tyrosine kinase inhibitor

Islet cell tumors of the pancreas

Registration in US; approved in EU in December 2010

Axitinib

VEGF tyrosine kinase inhibitor

Renal cell carcinoma

Phase III

Bosutinib

Abl and src-family kinase inhibitor

Chronic myelogenous leukemia

Phase III

Crizotinib

c-MET-ALK inhibitor

Lung cancer, cancer^b

Phase III

Inotuzumab ozogamicin^a

Aggressive non-Hodgkin lymphoma

Phase III

Neratinib

Pan-HER inhibitor

Breast cancer

Phase III

PF-00299804

Pan-HER inhibitor

Lung Cancer

Phase III

Sunitinib malate

Multiple tyrosine kinase inhibitor

Renal cell carcinoma, adjuvant

Phase III

Temsirolimus

Islet cell tumors of the pancreas

Renal cell carcinoma

Phase III

Axitinib

FKBP-rapamycin-associated protein

Lung and thyroid cancers

Phase II

Inotuzumab ozogamicin

Indolent non-Hodgkin lymphoma

Phase II

PD-0332991

Cancer

Phase II

PF-00299804

Cancer

Phase II

PF-01367338

Cancer

Phase II

Tremelimumab

Genitourinary and gastrointestinal cancers, melanoma, renal cell carcinoma^b, pancreatic cancer^b

Phase II

^aThe project is either new or has progressed in phase since Pfizer's previous portfolio update.

^bAdditional indications in phase I.

New molecular entity

New indication or enhancement

ALK indicates anaplastic lymphoma kinase; c-MET, mesenchymal-epithelial transition; HER, human epidermal growth factor receptor; VEGF, vascular endothelial growth factor.

This focused approach has already proven its worth in 2011. In August, the FDA approved crizotinib for the treatment of patients with ALK-positive NSCLC. To ensure that only patients with the ALK-positive form of the disease receive the drug, the patients are required to undergo a genetic test. Even though the American Society of Clinical Oncology estimates that only about 8% of NSCLC patients are ALK-positive, Pfizer claimed that crizotinib will succeed because it will be prescribed only to those most likely to benefit from it.

“Our oncology division is determined to find which of these therapeutic agents are most likely to benefit the patients,” said Bruns.

In addition to the FDA’s approval of crizotinib, in August the European Medicines Agency accepted submissions for both crizotinib and bosutinib. Bosutinib is an investigational, orally available dual src and abl kinase inhibitor with minimal inhibitory activity against c-kit and PDGFR. Bosutinib is being developed to treat patients with Philadelphia chromosome-positive (Ph ) chronic myeloid leukemia (CML). Based on clinical trials, it is believed that bosutinib inhibits CML-signaling cells, thereby slowing the disease’s ability to grow, survive, and reproduce.

Since Pfizer currently has 8 phase III trials underway and axitinib is being reviewed by the FDA, the company could see a number of key approvals in 2012. In addition, Xalkori will become more readily available and more prescribed as appropriate patients are identified through genetic tests. This will allow the company to understand appropriate ways of approaching targeted patient populations.