Summary
1) BiovaxID shows a 100% improvement in DFS at 3 years (p=0.24) 2) BiovaxID shows an improvement in median overall DFS with a significant P value (p=0.047) 2) This is the first lymphoma vaccine with a suggestion of activity. 3) BiovaxID shows evidence of activity despite the failure of 2 other lymphoma vaccines made by Genitiope and Favrille.
Analysis
Biovest has released preliminary data from their phase III trial of BiovaxID in NHL. They report an improvement in DFS by more than 1 year (p=0.047) with a 100% improvement at the 3 year mark in DFS (p=0.024). There is a general feeling that lymphoma vaccines do not work by virtue of the failure of Genitope and Favrille's similar lymphoma vaccine trials. One must remember however that Genitope and Favrille used PCR/recombinant technology to create their small man made peptide vaccines that they hoped would look like the real lymphoma target. This technology is dependent on their "smarts" in knowing what part of the cancer protein should be PCR'd to make the smaller peptide vaccine and in "luck" that their small man made peptide will fold correctly to look like the malignant target. Failure of either of these 2 steps and you end up with a vaccine that is either the wrong target or will not stimulate the immune system. Biovest approached the issue using hybridoma technology. In this situation, they essentially captured and cloned the whole target protein from the patient's individual cancer. There is no guessing as to whether their vaccine looks like the real thing. By viture of their different methods of creation, one would expect Biovest to have the more active vaccine and would be more likely to succeed in stimulating the immune system. In addition, the 3 phase III clinical trial were set up differently. Biovest only allowed patients with complete remission to continue on and receive vaccine whereas the others allowed patients with partial remission to be vaccinated and counted. While this may seem like a small issue, one must ask where does one think a vaccine will work best? Would it work in a patient with large amounts of active cancer or would it be best in a patient with no visible cancer. The issue is patients with large amounts of lymphoma would already show large amounts of "tumor protein" similar to the vaccine. If that "tumor protein" could not stimulate the immune system they why would giving more man made "tumor protein, (AKA vaccine)" do any better. Finally, patients with active immune system cancers such as lymphomas may have altered or suppressed immune systems making their immune reaction potentially aberrant. By using only patients in complete responses Biovest set themselves up with the best patient population with which to see a response.
Bottom line: I believe Biovest's data needs to be assessed independently from that of Genitope/Favrille. The failure of Genitope/Favrille has little bearing on Biovest's vaccine and trial. There are significant differences in vaccine technology and trial design with Biovest having the upper hand. With the borderline P value from the released interim phase III data and other issues still outstanding, all eyes will be on the final data. BiovaxID will succeed or fail based on its own merits. Just do not assume BiovaxID will fail based on the failure of Genitope and Favrille.
