We previously discussed the concept of DNA vaccination for antigen-specific modulation of the immune system in conditions of autoimmunity such as multiple sclerosis. In essence, it appears that DNA-based administration of the same proteins that are targets of the immune system during autoimmunity seem to suppress the immune response in a specific manner. This is different than other immune modulators such as anti-CD25 antibody or Tysabri which suppresses in a non-specific manner.
A published Phase I/II trial of BHT-3009, Bayhill Therapeutics DNA vaccine for myelin basic protein in 30 patients with either secondary progressive or relapse-remitting multiple sclerosis was performed in which antigen-specific immune modulation was seen, and safety of the vaccine was demonstrated. Here we will discuss a larger trial by the same group that was recently published (Garren et al. Phase 2 trial of a DNA vaccine encoding myelin basic protein for multiple sclerosis. Ann Neurol 2008 May;63(5):611-20).
This trial was much larger than the previous trial (267 patients), and was limited to patients with relapse-remitting multiple sclerosis. The patients were randomized to receive either placebo, or two doses (0.5 mg and 1.5 mg) of the DNA vaccine (BHT-3009). DNA vaccination was performed intramuscularly at the timepoints of initiation, after 2 weeks, after 4 weeks and subsequently given for every month until the 44th week.
The data demonstrated that in comparison to patients receiving placebo there were no positive effects of the 1.5 mg dose. In contrast, the 0.5 mg dose caused a 50-61% reduction in new lesion formation as detected by MRI and profound reduction of anti-myelin antibodies.
These data support further expansion of the DNA vaccine approach into phase III clinical trials. These data, as well as other antigen-specific tolerogenic vaccines may be one of the reasons why entered a $350 million deal with Genetech.