[The following was posted over at Yahoo!. If I remember correctly the person who has posted this is an employee at Millennium or at least working with them. He has proven to be a balanced and reliable poster in the past].
some thoughts
by: boronate 05/08/03 09:13 pm
Msg: 35075 of 35084
Hello friends,
The data submitted by Mlnm for Velcade’s marketing approval are derived from three separate Phase II clinical trials. There is little, if any ambiguitiy to the data, as the amateur analysts here are suggesting.
1. In the largest SUMMIT Trial, the data not only included the primary endpoints of response rate but also median survival as well as TTP (time to tumor progression). The surrogate endpoints data were collected by independent laboratories that measured changes in a protein secreted by malignant cancer cells, and the results were analyzed by an independent contractor using the most stringent criteria known as Blade, criteria that surpassed any previous trial analyses, including those done with Revimid. So the results using the surrogate (amount of cancer cell proteins) endpoints of response rate and TTP are as unassailable as they can get. Unlike solid tumor trials where decrease in tumor size and number are harder to quantify, the myeloma cancer cell protein determination is straightforward and is not dependent on subjective interpretation. It is true that this PII trial is not a comparative trial, and there is always the uncertainty that patient selection may skew the results. However, the survival benefit of responding patients clearly surpasses those that did not respond to Velcade. Thus, there is an internal comparison among the responding and not responding patients. The survival benefit also indicated the validity of the surrogate endpoints. That is, the respondents, who have less myeloma proteins, survive longer. Thus, there is a statistically significance to the lowering of myeloma protein to survival.
The trials were done in over 10 clinical centers with investigators that are considered the leading experts in Myeloma. They will not be going around trumpeting Velcade if they have concerns with the analysis and interpretation.
2. In the second PII trial, which has a smaller patient population (~50), the patients are mostly those who relapsed after front line therapy. In this case, the prediction is that, if Velcade is effective, its response rate should increase with this group of patients. While there is no ironclad theory behind this assumption, it is borne out by every cancer drug development known. Again, the results here show that the response rate is around 50%, a figure that is better than the 30% or so response rate in the more heavily treated patients in the SUMMIT trial.
3. The third PII trials are for patients that failed the enrollment criteria for the current PIII or came in between the PII and PIII trials. These are mostly patients in the category of the SUMMIT trial.
4. It is true that the response rates in the three Gleevec trials are higher. But these patients were selected on the basis of having the target, which is about 40% of CML patients. Without this preselection, Gleevec response rate will only be slightly higher than that shown in Velcade. It really shows the power of personalized medicine at its best. It will take years for the Gleevec PIII trials to be completed to examine survival benefit. Velcade is not Gleevec which is really “personalized medicine” at its best, but it is damn close to being a miracle drug for many MM patients. (continue)
Re: some thoughts
by: boronate 05/08/03 09:13 pm
Msg: 35076 of 35084
5. There have been some misconceptions to the use of PIII data to support the marketing application. The PIII patients are not the same as the PII patients. These are patients that have other options. It will be used to push Velcade into front-line treatment at a later time as Decadron is considered a front-line treatment although it is not frequently used as such.
6. In terms of pricing of Velcade, it is instructive to know the cost of current treatment. The front line treatment of chemo (4 agents) costs about $50,000. The increasingly adopted high dose chemo together with stem cell transplant costs about $150,000. this higher cost is accompanied by increased survival from 45 to 58 months. The survival benefit of Velcade, for the respondents, is not that far off from this difference. The lowest cost treatment currently is thalidomide, which comes in at around $15,000. I know this, Mlnm knows this and people in re-imbursement know this. So set a price for treatment yourself based on these numbers. |
