My overriding impression of large cap Pharma R&D from the 2013 annual meeting of the American Association for Cancer Research (AACR) was that Novartis and Genentech remain the front-runners in cancer drug development, with Pfizer very much up and coming.
AstraZeneca, however, reported data for several drugs that have or soon will be going to “dog drug heaven.” If AstraZeneca receives an “A” for effort but a “C” for execution, then Bristol Myers Squibb (BMS) was in my view a “D” at AACR with little presence.
What interests me at a meeting such as AACR is trying to spot some of the early trends in the 6,000+ posters, and identify new products in development that are worth watching. I was generally impressed by the quality of the posters on Pfizer cancer drugs.
One of the Pfizer compounds that attracted my attention in the AACR posters (before news of its FDA Breakthrough Therapy designation in breast cancer) was palbociclib (PD-0332991), an inhibitor of cyclin dependent kinases (CDK) 4 and 6. Karen Sheppard from the Peter MacCallum Center Centre in Melbourne, Australia (abstract #3416) presented a poster on genomic alterations of the CDK-4 pathway in melanoma and evaluation of the CDK4 inhibitor PD-0332991. According to Sheppard:
“Genomic alterations in the CDK4 pathway are frequent and are associated with worse survival”
Sheppard’s preclinical research supports the evaluation of CDK4 inhibitors in melanoma, so it will be interesting to see if clinical data supports the development of palbociclib in this indication. In the meantime palbociclib appears to be a winner in breast cancer.
Another Pfizer compound to watch is dacomitinib (PF-00299804) a second-generation inhibitor of the pan-epidermal growth factor receptor (EGFR) family of tyrosine kinases (ErbB family). Previously, Pfizer had another pan ErbB inhibitor in development (neratinib) from their merger with Wyeth, but licensed it out to Puma Biotech and focused their development efforts on dacomitinib instead. That may well turn out to be a smart R&D decision.
A poster presented by Brett Broussard from the University of Alabama at Birmingham (abstract #2446) showed the effects of dacominitib on pancreatic ductal adeoncarcinoma (PDAC) and cancer-associated fibroblasts. In his abstract, Broussard notes a possible reason why anti-EGFR therapies may have had little effect in PDAC:
“Indirect activation of Epidermal Growth Factor Receptor (EGFR) signaling through ErbB3 heterodimerization and stromal ligand production has been shown to act as an escape mechanism for EGFR directed therapies.”
Broussard’s research showed that dacomitinib targets multiple ErbB receptors, including ErbB3, and was an effective inhibitor of pancreatic ductal adenocarcinoma (PDAC) cell proliferation and tumor progression in vitro and in vivo.
He told me that Pfizer are expected to start phase 2 trials in pancreatic cancer with this compound later this year. There remains an unmet medical need in pancreatic cancer, so while it is too early to evaluate dacomitinib’s potential as a new treatment option, it is good to see translational research being done and new compounds entering the clinic.
Overall, my take home from AACR was that Genentech and Novartis remain the powerhouses of cancer drug development. I was impressed by the number and quality of the posters from Pfizer Oncology R&D and left the AACR poster hall thinking that Pfizer may well have some new cancer products in development that are well worth watching.