Wednesday, March 27, 2002 

To whom it may concern:

The purpose of this text is to share patient perspectives of the FDA decision to delay the approval of Bexxar.  The letters attached clearly show that patients are keenly aware that they require an array of treatments to stay alive and maintain quality of life.  The letters also demonstrate impatience, which is based on the sobering facts. Briefly, it is hell to have indolent lymphoma, or any cancer that’s incurable, and time lost means lives lost.

Patients and caregivers are confused and frightened by the delay of Bexxar, as it appears to contradict numerous published reports on it’s safety and efficacy. Since it appears inevitable that Bexxar will eventually win approval, the patient community wants to understand the reasons for the delay, and they want to express their fears and perspectives of why they need the drug – a drug that the entire medical community has believed for years will be approved eventually. Others have noted that the full potential of a therapy is discovered after approval—in determinations of how it fits with and complements other treatments and in which treatment settings.  Delays in approval, thus impedes development of best practices with the new agent as well, and deprives patients who may not have any better alternatives. Patients understand that approval of a drug does not mean that there are not risks associated with the treatment, or that the drug will be suitable for all patients.  They want to be informed about risks and to have choices.

 Perceptions of patients gathered from publications and presentations at professional conferences.

·        Bexxar appears to be effective and safer than the majority of standard treatments. Importantly, it appears to double response rate and time to progression in pts refractory to chemo. Journal of Clinical Oncology  2001;19:3918-3928.

·        Bexxar can be particularly valuable for obtaining durable responses in some patients who receive it as initial treatment in combination with chemotherapy.

·        Bexxar has unique properties that distinguish it from Zevalin, including: migration tendency to thyroid, instead of bone marrow & liver; shorter wavelength; more accurate dosing; and shorter half life. The unique properties of Bexxar could make it more appropriate than Zevalin in some circumstances, depending on the patient’s treatment history, tumor burden, bone marrow involvement, etc.

·        Bexxar seems to be overwhelmingly safer than Campath, a cancer drug which recently won approval. “In the most recent study of Campath, a 30% mortality rate was observed, with roughly half of those deaths attributed to therapy-related complications, including hematological toxicities such as bone marrow hypoplasia.  In the same study, there was a high incidence of infection among those treated with Campath.”

·        Many patients reason that Bexxar could not have serious side effects because the Expanded Access program that began in 1998 continued without interruption for 4 years. Patient participation in that program resulted from the perceptions noted here and the belief that safety issues are better known the longer a drug has been used.  Bexxar has been administered to patients since 1990.

Potential side effects of the delay of Bexxar:

1.      Pts with incurable cancers recognize the financial risks that companies face when seeking to develop new cancer drugs. We also know that it’s essential to encourage the drug development process because we are certain to die of our disease unless companies are willing to take the risks.

2.      Therefore, it is critical that the FDA does not appear to be inconsistent in it’s decisions. Furthermore we believe the agency has a responsibility to move clinically useful agents with unique properties through the system in a timely manner.  Many patients have asked why the undisclosed reasons for the delay took so long to be discovered, and so surprised the sponsor. Other drug sponsors may have the same concerns.  It should be noted that most, but not all, patients understand that non-disclosure by the FDA is the law and not the fault or decision of the FDA

3.      There is a concern that the delay of Bexxar will significantly weaken the incentives provided by the Accelerated Approval path because it signals to companies that what is defined as “unmet need” can evaporate if similar competing agents win approval during the conduct of the application and testing process.

4.      If the delay of Bexxar is associated with failures specific to the Expanded Assess trials, it may discourage availability of other compassionate use programs.  Patients who eventually fail to respond to standard treatments, which is the norm for indolent lymphomas, will die as a result.

In conclusion, continuing cancer deaths and diminishing response to approved toxic treatments firmly establishes the urgent need for a variety of novel targeted treatments for pts with indolent lymphoma. Published evidence of efficacy and safety for Bexxar in comparison to standard treatments and the recently approved agent Campath, have caused deep confusion about the standards and methods required to win approval. We now also fear the loss of the Bexxar Expanded Access program, and the impact it may have on compassionate use programs for other agents. Finally, this decision underscores the need to find better ways to encourage, guide, and inform the drug sponsors every step of the way, else we needlessly impede the development of new cancer drugs. I believe we should view the costs of disincentives to new drug development to be particularly dangerous and incalculable. 

It is our hope that a compromise will be reached that will assure continuing access to Bexxar for patients who need it; perhaps Bexxar can be approved through the Accelerated Approval path with provisions to run a number of Phase IV trials (including post marketing surveillance) to address remaining questions.

Thank you for your attention to this matter.

Karl Schwartz, 

Patient representative, ODAC