Passion, Compassion, Commitment: An Interview with Renzo Canetta

Renzo M. Canetta, M.D., is vice president of Global Development, Oncology Global Clinical Research. He recently celebrated his 25th anniversary with Bristol-Myers Squibb.

Question: It's been 25 years. Does it seem like 25 years?

Canetta: It seems like yesterday. Bristol-Myers Squibb and I still have the same passion for clinical research, the same compassion for the cancer patient and the same commitment today that we both had when I joined the company 25 years ago.

Question: Why did you enter the field of oncology?

Canetta: As is true for many people who undertake a medical career, I wanted to help people, and so I went to medical school at the University of Milan. What eventually interested me in hematology and oncology is the fact that clearly cancer is a disease that poses very radical questions in terms of scientific approach, clinical trial methodology, public health policies and, last but not least, in terms of compelling human aspects for patients and their families.

Question: What was your early work in oncology?

Canetta: I worked as a clinical investigator at the National Cancer Institute in Milan for six years. At the time our group was involved in trials that changed medical practice in the treatment of important diseases; these succeeded in prolonging survival in women with breast cancer who received chemotherapy after surgery. We were also working in trials for Hodgkin's Disease. We verified in clinical trials that a new regimen of drugs, called ABVD, improved the cure rate for Hodgkin's Disease and introduced the concept that non-cross-resistant chemotherapy.

Question: So, early in your career you were doing significant work in academia. What brought you to industry at Bristol-Myers Squibb?

Canetta: Out of the blue I got an offer from what used to be the International Division of what was then Bristol-Myers Company in New York. In 1980, the company had just launched Platinol®-AQ (cisplatin for injection), and was preparing to launch VePesid® (etoposide). Bristol-Myers was on the brink of making a major burst into oncology. That, and the fact that the company was genuinely committed to the field of oncology at a time very few other companies were, is what attracted me to the company.

Question: And now, today, we're making another major burst into oncology.

Canetta: The situation then was very similar to where we are today. This year, again, we have received with Sprycel® (dasatinib) the regulatory approval for a new, important drug, and have several additional drugs in the final stages of development and about to be brought to general availability. That's why I'm as excited today as I was 25 years ago.

Question: The additional drugs you're talking about are ixabepilone, vinflunine and ipilimumab.

Canetta: Yes. Ixabepilone is an internal discovery currently in Phase III trials and it's a very exciting compound with important biological characteristics. This compound has shown potential non-cross-resistance with the taxanes, TAXOL® (paclitaxel) and Taxotere.

Ixabepilone is a different molecule, a new class of antineoplastic drugs being developed in an effort to overcome taxane resistance. In addition to that, early preclinical studies indicate that this compound may have a broad spectrum of anti-tumor effects. And whereas we have a very large program in breast cancer -- in fact, the largest program ever set up by a sponsor for a registrational program for metastatic disease -- we have a clinical development program planned to investigate this compound in a number of additional tumor types. We are also developing new formulations and schedules to help manage adverse events of the compound.

The second compound, vinflunine, was licensed in by Bristol-Myers Squibb from Pierre Fabre Médicament, and this compound is already in Phase III trials for bladder cancer. Constipation and myelosuppression are main adverse events reported. We are partnering with Pierre Fabre to expand the development of the compound, as well as to improve its utilization assuming it is approved.

The third drug is an interesting monoclonal antibody called ipilimumab that we licensed at the end of 2004 from Medarex. Medarex has conducted Phase I and Phase II trials, and we are now together in Phase III trials for melanoma, which is a deadly disease when it metastasizes. We believe that this compound is promising in melanoma and, based on early study results to date, also in a number of other tumor types.

In addition to the three compounds that we just mentioned, there is the very rapidly maturing data on our SRC/ABL kinase inhibitor SPRYCEL. This has been a story of an incredibly rapid preclinical and clinical development. It was evident at the preclinical level that this molecule has the potential to successfully treat CML (chronic myeloid leukemia) cells that had mutated to become resistant to treatment with imatinib (Gleevec/Glivec). The other relevant characteristic of these new treatments is the potential to transform a disease that used to be extremely aggressive, acute and lethal in the majority of the patients into something that may be controlled over time. We will be watching for this with great interest. We are continuing research on the role of Sprycel in other hematologic malignancies, earlier stages of CML, and in the more common solid tumors. We believe the potential is great, and personally, having been trained in the early days of my career as a hematologist, I am highly gratified by the early results of
SPRYCEL.

Question: You joined the company when important oncology medicines were launched. Now, 25 years later, other potentially important oncology products are in late development. Sandwiched in between these two times, almost exactly, is the development and launch of TAXOL.

Canetta: The development of TAXOL was quite an experience. Before Bristol-Myers Squibb got involved, there was no possibility to treat more than 100 to 200 patients per year with TAXOL because of a dreadful lack of supply. And yet the drug appeared to be more and more important medically. So in the span of a very short time -- six months from the signing of the collaborative agreement with the U.S. National Cancer Institute -- and thanks to the fact that everybody in Bristol-Myers Squibb really put in tremendous effort, we were soon able to treat 1,000 to 2,000 patients per year. Ultimately, TAXOL became the first billion dollar cancer drug. This is a commercial success that was driven by the important medical results obtained with the drug.

Question: We have not had a new global oncology compound since TAXOL. And now, suddenly, we have the potential for launching several over a short period of time.

Canetta: That is correct. Our organization has been very proud over the past four years to have launched eight new products in five therapeutic areas. The challenge in oncology in the next few years is that we will have to submit and support the launch of potentially four compounds from the same therapeutic area over a very short span of time. The first one of these four, Sprycel, has already been approved both in the U.S. and in Europe, as well as in several other countries.

Question: We've had a strong oncology pipeline in the past, and we have one now. Why the slump in the 1990s?

Canetta: In the pharmaceutical industry, you go through cycles. This is true for the industry as a whole, this is true for Bristol-Myers Squibb, and is true also for individual disease areas. What is not cyclic is the commitment of the company to certain types of diseases, and it is clear to me that Bristol has been committed over all these years to a presence in oncology. It is not by chance that the vast majority of the anticancer drugs that are currently present in our development pipeline are all internal discoveries. And we have targeted agents, we have anti-angiogenesis agents, we have biologics, we have immunotherapeutic agents, and we have recently brought to the clinic even a new hormonal agent.

Question: During your 25-year career at Bristol-Myers Squibb, you've been involved in studies that led to the approval of 14 new cancer medicines, and two antiviral agents, as well as many other supplemental approvals within and outside of oncology. This record of accomplishment is perhaps unmatched in the field. What are you most proud of during that period of time?

Canetta: The first thing that comes to mind clearly is the patients that ultimately ended up benefiting from the work that we have done at Bristol-Myers Squibb. The second thing is the people that I have been working with, and the way they're developing in their professional and personal growth. Also, I am proud that we have made an impact not only on medical treatment but also on regulations. We made a major contribution to the understanding of the role of salvage therapy, both in cancer and in HIV disease. And it is also based, in part, upon our pioneering experience at BMS that the U.S. government enacted regulations that now allow for a more rapid approval of important drugs for life threatening diseases.

Question: Will there ever be a cure for cancer?

Canetta: I see more and more patients do well every day as we treat them in earlier stages for the disease and with novel, powerful treatments. To eradicate cancer, that will take more time and more research. To me the problem is really not how close or how far is the cure of cancer but is the quality of the effort that goes into addressing a disease that is part of life, not necessarily part of death.

Question: What keeps you motivated to go to work every day?

Canetta: That clearly the job is not finished and that every day I work I get to learn new things, and that's what keeps me going. What I found in Bristol-Myers Squibb is a correspondence of my personal aspiration and the mission of the company, and working together with people who share this passion and compassion is the best experience I can hope for.

Please click on product name to see the full Prescribing Information for Sprycel® (dasatinib), and including the boxed WARNINGS for Platinol®-AQ (cisplatin for injection), Taxol® (paclitaxel), and VePesid® (etoposide).