Goal one: curing cancer
Life is stranger than fiction
As I read the school paper (many years ago), I wondered whether my classmates knew better than I what the future held. The prophecies they had written for our high school class included one where I ‘discovered a cure for cancer’. At that time I was not entirely sure that I would become a physician and had not even considered hematology/oncology or clinical research. Today, I suppose that my being responsible for the development (clinical and regulatory) of rituximab fulfills that prophesy Citation[1,2]. I had never thought of leaving my native Puerto Rico. Years later, after living in the continental USA and Europe for over 12 years, I received a call in Geneva, Switzerland, offering me a job with a small biotechnology company in San Diego, California; and the rest is history. One of my goals (the most important and the most ambitious) as a clinical cancer researcher, had been to develop an agent that could be curative for cancer patients. Rituximab became the first monoclonal antibody approved for the treatment of cancer. In combination with adriamycin, cyclophosphamide, vincristine, prednison (CHOP) chemotherapy it increases the cure rate, in patients with diffuse large cell lymphoma, by approximately 50% over that of CHOP alone Citation[3,4].
Andrew C von Eschenbach, who has directed the US National Cancer Institute (NCI) for over 4 years, has voiced a similar goal for himself, the NCI and truly for the entire oncology community. Some have interpreted this goal as ‘eliminating suffering and death due to cancer by 2015’, or, ‘curing cancer’ Citation[5]. The statement he has made is actually a bit more conservative – ‘making cancer a chronic disease that patients can live with, rather than a fatal disease’ Citation[6]. Von Eschenbach, a urologic surgeon, is a cancer survivor himself, having had melanoma, prostate cancer and basal cell carcinoma. He has roots in Texas, a long-standing relationship with the Bush family and strong academic credentials. He joined the MD Anderson Cancer Center (TX, USA) as a urologic oncology fellow in 1976 and was named chairman of its urology department in 1983. He was President-elect of the American Cancer Society when President Bush tapped him to head the NCI.
Goal two: accelerating cancer drug development
Having fulfilled my first goal, I have dedicated all my efforts over the past 5 years (since my retirement from IDEC Pharmaceuticals where I was the chief medical officer) to identifying ways to accelerate cancer drug development, review and approval. This is the goal of the research institute that I have founded and funded. The Neoplastic and Autoimmune Diseases Research Institute (Rancho Santa Fe, CA, USA) was established in 2001 to conduct research on the drug development and regulatory approval processes for cancer and immune therapies; and to provide advice and guidance on these processes to regulatory agencies, the NCI, academic institutions, patient advocacy groups and the pharmaceutical industry. The institute’s goal is to foster the expeditious and efficient development, review and approval of new therapies for these diseases. I have pursued this goal through participation in the US Food and Drug administration (FDA)’s Oncologic Drugs Advisory Committee (where I am the industry representative), consulting for the NCI and advising pharmaceutical industry via membership in scientific advisory boards. Patients and patient advocacy groups are critical to the process and recognizing this, I have been a member of the Lymphoma Research Foundation and National Coalition for Cancer Survivorship boards.
There are many ways to accelerate cancer drug development, review and approval. The most important and one needing urgent attention is the regulatory process. Nothing other than FDA reform would have a greater impact on the (shortening of) development timelines and the (promptness of) cancer drug availability. The FDA, many in the media, the congress and even some clinicians have it all wrong. It should not be the FDA’s job to regulate and approve the optimal use, in combination regimens, of new agents. Identifying the optimal use of a new agent is a formidable task that usually extends over 20–30 years. This is the responsibility of the oncology community and not the FDA Citation[7,8]. The FDA should evaluate cancer drugs to ensure reasonable safety and should promptly approve them if there is reasonable evidence of clinical activity in early Phase II trials. This would make promising new drugs available early on to those patients that can benefit from them and would also make them available broadly to the oncology community to then undertake the lengthy process of identifying and optimizing their use within combination regimens.
Recently, upon the resignation of Lester Crawford, von Eschenbach has been named acting FDA commissioner. The media have painted him as an activist and quoted him as saying that promising new drugs should be made available as rapidly as possible especially to patients with life-threatening diseases who are often willing to accept greater risks than people with less serious illnesses Citation[9]. They have also painted him as a conservative. He ‘sees the need to consider’ changes designed to streamline the process for important new treatments, ‘within the context of continuing to assure their efficacy and safety’, but ‘speed does not mean recklessness’. He has no plans to sharply change the direction of the FDA and hopes to bring stability by relying on experienced staff and continuing initiatives begun under Crawford and his predecessor, Mark McClellan Citation[5]. Clearly, the media have no idea of where von Eschenbach is heading. A more realistic and better informed journalist has stated that ‘whether he operates in a permanent or acting capacity, von Eschenbach will not come equipped with a magic wand, and any honeymoon may be short. But he probably brings enough goodwill to be given a chance to make a mark’ Citation[10].
The bottom line
Von Eschenbach has a golden opportunity to make a mark for himself and to benefit cancer patients that so desperately await those drugs that may represent cures. No one can be in a better position to change the FDA and accelerate cancer drug development, review and approval. He has a number of advantages. First and foremost, he is a cancer survivor. He knows cancer as an oncologist and also as a patient. Additionally, he has management experience both at MD Anderson and at the NCI. He is well connected with the current administration and appears to be well regarded in congress. Likewise, he has a number of disadvantages. He comes from Texas and is well connected with the current administration. He has no regulatory experience. He has no pharmaceutical experience. He has never developed a drug through Phases I, II and III; and much less taken it through the regulatory process to an approval. The key questions will be, how fast can he learn? Is he truly a good manager? How effective will he be when facing the FDA’s imposing bureaucracy? He has stressed the importance of collaboration among universities, pharmaceutical companies, biotech companies and nonprofit organizations. Will he be able to make all of this happen? Will von Eschenbach be able to meet both goals: curing cancer and accelerating cancer drug development? I, for one, am optimistic and in favor of not just giving him this opportunity but of supporting him in every possible way. You see, like von Eschenbach, I too am a cancer survivor. Onwards, Andrew, too many lives depend on your success.
‘For myself I am an optimist, it does not seem to be much use being anything else.’
Winston Churchill
Information resources
Additional information is available at www.FDA.gov (Accessed November 2005)
References
- Grillo-López AJ. Rituximab: an insider’s historical perspective. Semin. Oncol. 27(6) (12 Suppl.), S9–S16 (2000)
- Grillo-López AJ. Rituximab: the first decade (1993–2003). Expert Rev. Anticancer Ther. 3(6), 767–779 (2003).
- Coiffier B, Lepage E, Briere J et al. CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large B-cell lymphoma. N. Engl. J. Med. 346, 235–282 (2002).
- Sehn LH, Donaldson J, Chhanabhai et al. Introduction of combined CHOP plus rituximab therapy dramatically improved outcome of diffuse large B-cell lymphoma in British Columbia. J. Clin. Oncol. 23, 5027–5033 (2005).
- Acting FDA Chief Asserts a Need To Review Drug-Approval Process. Wilde Mathews A. The Wall Street Journal. September 26 (2005).
- FDA Commissioner Steps Down After Rocky Two-Month Tenure. Kaufman M. The Washington Post. September 24 (2005).
- Grillo-López AJ. The ODAC chronicles: part 3. The FDA’s philosophy and process for cancer drug evaluation and approval (Editorial). Expert Rev. Anticancer Ther. 5(1), 1–5 (2005).
- Grillo-López AJ. The ODAC chronicles: part 4. Hurdles pre- and post- accelerated approval (Editorial). Expert Rev. Anticancer Ther. 5(2), 197–200 (2005).
- Bush’s Choice for FDA. Chief to Keep Other Job. Pear R, Pollack A. The New York Times. September 25 (2005).
- Into The Breach At FDA. Usdin S. Biocentury, The Bernstein Report On BioBusiness. September 26 (2005).