Rosenthal, Eric T. - Special Correspondent
MACE L. ROTHENBERG, MD
Five years from the time that he first entertained thoughts of leaving academia for pharma, Mace L. Rothenberg, MD, reflected on his tenure at Pfizer, leading worldwide development of oncology drugs.
When we spoke at the end of 2008 (for an article published in OT's 1/25/09 issue), shortly before he started his position as Senior Vice President of Clinical Development and Medical Affairs for Oncology in the then newly restructured Pfizer business unit, he talked about the tradeoffs involved in giving up patient care and a well-established career as a clinical researcher at Vanderbilt-Ingram Cancer Center for industry.
He said then: “It [joining Pfizer] would allow me to benefit from the substantial resources of Pfizer to help guide development of a really top-rate portfolio of compounds on a worldwide basis. This struck me as being very different from any position I ever heard of before in the industry.”
Now, half a decade later, Rothenberg said that his expectations and goals were being fulfilled, even through a tough budget-cutting time that made clear to him what he now realizes is a misperception about the pharmaceutical industry.
He said that in 2010 when Lipitor's patent was approaching its end the following year and Pfizer was anticipating a significant loss of revenue from the cholesterol-lowering drug, he and other division chiefs were told they had to shear their budgets by 25 percent.
“The misperception is that pharmaceutical companies have lots of money. The budget I was given when I joined Pfizer did dwarf any other budget I had ever been responsible for, but the reality is that you never have enough money to do everything that you think is meritorious,” he said.
Rothenberg said that Pfizer's purchase of Wyeth four months after he came aboard added even more oncology drugs to the company's portfolio and that with the cutbacks that followed he was faced with having to whittle down the more than 30 oncology drugs under development and take some considerable cost-saving actions.
25% Budget Cut
“I was challenged to reduce my budget by 25 percent, and actually reduced it by 27 percent by cutting the overall size of the oncology portfolio by about half to about 15 drugs. But the quality of those left was very exciting, and I think it's been a good thing, since it has helped to focus our efforts on drugs that will help patients the most,” he said.
Rothenberg referred to these compounds as Pfizer's “innovative core,” drugs that were differentiated by showing great potential of activity in many ways. He said the cutbacks turned out to be beneficial because it forced the company “to ratchet up the intensity of review and raise the bar in order to have a drug proceed from laboratory toward the clinic or from one stage of the clinic to the next.”
He added that several compounds were outsourced to companies that were thought to be better able to provide the right focus and resources, including a PARP (poly ADP-ribose polymerase) inhibitor to Clovis Oncology; a pan-HER inhibitor (neratinib) to Puma Biotechnology; and a CTLA-4 monoclonal antibody (tremelimumab), to AstraZeneca.
And since he started at the company his group has developed and obtained regulatory approval for, among others, sunitinib (Sutent) for pancreatic neuroendocrine tumors (2011); axitinib (Inlyta) for renal cell carcinoma (2012); and bosutinib (Bosulif) for Ph-positive chronic myelogenous leukemia (also 2012).
Does Miss Patient Care and Academia, but…
Rothenberg said that although he does miss patient care and academia, being in industry has allowed him to make an impact he wouldn't have been able to make before, even though during his years as an academic-based researcher he helped develop and gain FDA approval for irinotecan (Camptosar) in 1996 and oxaliplatin (Eloxatin) in 2002 for colorectal cancer; and gemcitabine (Gemzar) in 1996 for pancreatic cancer.
“When I embarked upon a career in drug development 25 years ago I wanted to help bring more effective, less toxic drugs to patients. The highlight of my career has been being able to provide care to people with very serious illnesses and see the strength of their human spirit in very challenging circumstances.”
Developing closer collaborations with academic medical centers has been another of his goals, and he cited a research collaboration at UCLA with Dennis Slamon's laboratory as an example.
“Some companies have approached working with academic medical centers by giving large long-term grants for access to the best science that's not really that focused,” he said, adding that he believes that pharma and academia should be using their complementary skills to ask mutual questions, which is more productive and a better use of industry money.
He said he is gratified that even now, the impression he gets is that the people he has interacted with in academia still feel he's one of them. It's important never to lose one's objectivity or critical thinking no matter the change in direction or responsibilities, he said.
Noting the different perspective that he does have now, Rothenberg explained that as a clinical researcher, the measure of success was measured in another way: once a clinical trial met its primary endpoint, he would present the findings at ASCO, for example, then get them published, and that would lead to more funds for future research.
But now he has a much larger canvas and that success can be amplified into having an even greater impact on patients. “Everything is put in a larger context, and I have to ask the right questions: Does this move the drug closer to approval? What is its context in terms of other therapies? How relevant is it to us and to the rest of the world? What is the time frame for moving this forward? And how much money should we invest to bring it to market?”
He said other companies have people as smart and dedicated and with as many resources as his group at Pfizer, but what differentiates his team is “paying attention to what's happening elsewhere and having a sense of urgency”—“We want to know how and what others are doing relates to what we are doing. We incorporate all insights into our work and focus on the things we can do.
“In academia you are competing for grants against anonymous entities, but in industry you're competing against known entities, and it's not enough that a compound just be good, it also has to be first and best in its class, and we don't bring drugs forward just because the market is lucrative,” he said.
He said that after five years he does believe the trade-offs were well worth it, although he admitted that it took about 18 months before he understood the cycle of the company and could feel fully comfortable knowing what was expected of him within the new culture.
And, now he's ready for the next big change when Pfizer undergoes a restructuring next year that will integrate oncology, vaccines, and consumer health into a single unit with business in “emerging markets” merging with those in the United States, Europe, Japan, and South Korea.