[A566]Answers To All Questions

If you have been following this blog, you know I am on a campaign to get some answers from the FDA on how they evaluate potential new drugs. In this case, we are following the evaluation of a potential drug for my condition, CLL, and whether the evaluation is fair and based on the FDA and its outside consultants being conversant with the issues CLL patients and expert hematologists face every day. Basically, we are trying to a see if the process gives us patients appropriate opportunities to have potentially life-saving or life-extending drugs.

You may recall, I actually went to Washington, D.C. to testify as a patient advocate as an FDA advisory committee was evaluating Genta's drug, Genasense. I came away feeling both the FDA presenters and several committee members were not giving the drug and the sponsor their due and that patients were losing in the process.

The FDA assured me they had consulted with CLL experts, even though a big lineup of them were there to support the application for approval and further study. The FDA would only tell me who they consulted with if the sponsor, Genta, okayed it. Genta did and yet the FDA still has been slow to give me any information. I heard from them today, and they said they had been delayed as they consulted with internal attorneys. They asked me to stay tuned.

However, on the Genta side, the company has provided me with detailed answers to sophisticated questions posed by readers of my blog, and I will excerpt them below. Many of you have written in with questions about Genta, Genasense, and their history with the FDA and study data. So, in an effort to keep you informed as we weigh in as patients, here goes:

Issue #1

Did Genasense fail to live up to expectations and provide only marginal benefit?

?20% difference was not the agreed upon goal for the Genasense CLL study. The ??goal?? was to achieve a statistically significant difference in the CR/nPR endpoint. That goal was achieved. The 20% was an estimate used only for determining sample size ? in this case we estimated that by examining historical information before we started the study that the control arm would yield a 24% response. Again, this estimate was based on historical CLL clinical trials data. The Genasense Phase 3 randomized clinical trial showed that the control arm response was actually only 7% in a rigorous study. This trial, being the first randomized study in relapsed or refractory CLL, used rigorous assessment criteria and therefore may have established a new benchmark for control arm response rate in CLL. In addition, the company estimated that Genasense would improve control results by a factor of 1.8. The trial showed Genasense improved that rate by a factor of 2.5, much larger than projected.?

Issue #2

Was the FDA and Genta Fighting About Confirmatory Study Details?

?There were no substantive outstanding issues on the SPA. The last item was an FDA request for more clarity on how the independent review for response would be conducted. There was of course, understanding that the trial would be confirmatory after accelerated approval, and that would still be the company's intent.?

Issue #3

Was Genta and the FDA at odds about what the endpoints were supposed to be for the Study that was presented?

?The FDA agreed in writing that: ??durable complete responses supported by symptom benefit? are acceptable efficacy endpoints. (Dated from an FDA correspondence on 1/9/02). FDA stipulated that response rate, by itself, would not suffice for full approval. The company had always stipulated that we would be filing for accelerated approval, and that there were very substantial data to indicate CR/nPRs were highly beneficial for patients. We confirmed that finding in our trial.?

Whew! I know this is technical, but it speaks to the heart of issues that companies fight about with the FDA. It's important for some of us with science backgrounds to try to understand and to monitor the process. Otherwise, there's always the chance some potentially beneficial drug will be killed because a bureaucracy or a powerbroker lined up against it and we didn't speak up.

I don't mean to say the FDA is necessarily unfair. I just don't know. I can't wait to hear their side of this and I bet there are thousands of CLLers and other patients who are following this saga closely too.

In the end, we need to insist, as a community, to make sure we are protected. But we must also insist that we are given hope with new therapies and that our governmental processes are doing their very best for us, the taxpayers.

Because of my business endeavors, there are a few things you should know. HealthTalk has, in the past, produced programs on CLL treatment that were sponsored by unrestricted grants from Genta, the developer of Genasense. While there are no current or planned programs, you should know that the possibility of future programs exists. In addition, I now run a company called Patient Power that received an unrestricted grant from Genta to facilitate the travel of three people (myself, a CLL patient's family member, and another CLL patient) to the public hearing. Both at HealthTalk and at Patient Power, Genta has neither prompted nor had any control or influence over what we say or write.

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