|In 2000 and 2001, a drug called Erbitux received much publicity as a hope for patients with colorectal cancer. The publicity was due to preliminary data, and resulted in large increases in stock prices for ImClone, the developer of the drug.
On Dec. 28 2001, the FDA rejected ImClone's application for Erbitux. The "refusal to file" letter was not publicly released because of regulations limiting public release of proprietary trade information. ImClone indicated the the rejection was due to minor, easily-fixed problems.
On Jan. 4, 2002, "The CancerLetter" printed a story based on a leaked copy of the FDA's "refusal to file" letter. The letter indicated that ImClone's application problems were substantive and would take significant effort to resolve.
The discrepancies between what FDA had told ImClone and what ImClone told the public resulted in a Congressional investigation and numerous accusations of inside trading. Most of the attention focused on stock prices and inside trading. Cancer patients read reports of faulty trial design, wondering what it meant to them. To read an archive of the numerous articles covering ImClone's saga, go here.
On Feb. 27 2002, the "Wall Street Journal" printed an editorial critical of the FDA's handling of ImClone's situation. The editorial noted that, "the solution is ...for the FDA to disclose more about its drug reviews, as guidance to both investors and patients. People shouldn't have to wait for leaked letters to understand what the bureaucracy is up to ..." The following was written in response:
Wall Street Journal
To the Editor
In response to the Journal's editorial of February 27 2002 regarding ImClone Systems and the FDA, we would like to offer further clarification of some points and our endorsement of others. The ImClone 'scandal' and resulting scrutiny of the FDA cancer drug approval process offer an opportunity to improve the approval process, benefiting not only the pharmaceutical industry but also the public.
The editorial noted that, "the solution is ...for the FDA to disclose more about its drug reviews, as guidance to both investors and patients. People shouldn't have to wait for leaked letters to understand what the bureaucracy is up to ..." We agree.
The FDA regulations prohibiting disclosure of proprietary information were intended to protect corporate trade secrets and financial information. This prohibition has created an impenetrable shield behind which the FDA and drug companies hold their discussions.
If the FDA halts cancer research on patients for whatever reason, current regulations permit the FDA to communicate only with the drug's sponsor, usually a company or academic institution. The patients can get their information only from the drug company / institution. The FDA cannot correct misinformation or offer their perspective on the problems in the clinical trial to anyone without the drug company's permission.
Similarly, when a new drug gets in trouble because of its clinical trial design, investors and patients are not usually aware of this trouble until the FDA turns the drug down. For example, a drug company might disclose vague information about the trouble their drug has encountered, but the FDA is prohibited from confirming or refuting the drug company's account.
We challenge both Congress and the FDA to permit public disclosure at critical times in drug development. When the FDA turns a drug down or stops a trial for a life-threatening disease, the public's right to know trumps the protection of proprietary interest.
The editorial also noted that "it's hardly ethical to deny human study volunteers the best chance for survival based on available information." Again, we agree.
The HIV/AIDS community fought for and gained access to promising experimental treatments prior to final FDA approval. Cancer patients have also benefited from this early access. For example, 7500 patients used Gleevec before it was approved by the FDA. 5000 of these patients were not part of a formal research protocol; rather, they received the treatment under expanded access, which permitted pre-approval use. Expanded access is permitted or denied by a drug's manufacturer.
We also challenge the pharmaceutical industry to work with the FDA and patient organizations to expand access to experimental treatments for dying patients who are out of treatment options.
Finally, ImClone and the FDA have talked about this application for at least two years - why didn't ImClone understand how the research needed to be conducted? Why didn't they agree up-front about research and data requirements?
Thousands of cancer patients participate in clinical research to identify new therapies. These therapies take years and hundreds of millions of dollars to develop. Given this personal and financial investment, appropriate certainty must be built into the drug approval process.
Fortunately, the FDA has a new process which now allows the FDA and a pharmaceutical company to enter into a binding agreement about the clinical trial design. If all proceeds per the agreement and the data support the agreement, approval is almost certain.
We strongly urge pharmaceutical and biotech companies to take advantage of the opportunity that these special agreements present. We also urge the FDA to exercise appropriate flexibility without compromising solid safety and effectiveness standards.
One in three Americans will develop cancer in his lifetime. 500,000 Americans will die from cancer in 2002. We challenge everyone ... patients, the pharmaceutical industry, researchers, government ... to keep the war against cancer moving forward. Your life may well depend on the success - or failure - of our collective effort.
Marti Nelson Cancer Foundation
Abigail Alliance for Better Access to Experimental Drugs
To purchase a report on the ImClone situation which includes the text of the 'leaked' FDA Refusal to File letter, go to www.thecancerletter.com.