Avid Bioservices Inc (CDMO)

[freethemice]

The Stimuvax (L-BLP25) story. This is interesting. At first I couldn't figure out how the phase 3 trial could fail. From Dec 2012.
http://ir.oncothyreon.com/releasedetail.cfm?ReleaseID=727708

The updated phase 2b trial results were published in 2011 and showed good survival results. The trial enrolled both stage IIIB
and stage IV patients. Here are the survival curves. Top curve is all patients,
middle curve is stage IV, and bottom is stage IIIB.

Updated survival analysis in patients with stage IIIB or IV non-small-cell lung cancer receiving BLP25 liposome vaccine
(L-BLP25): phase IIB randomized, multicenter, open-label trial
J Cancer Res Clin Oncol (2011) 137:1337–1342

The phase 3 trial enrolled only stage IIIA and IIIB patients based on the phase 2b results. Seems like it should work fine.
Then I found this study.
A Multicenter Open-Label Study to Assess the Safety of a New Formulation of BLP25 Liposome
Vaccine in Patients With Unresectable Stage III Non–Small-Cell Lung Cancer
Clinical Lung Cancer November 2010

It turns out that the phase 3 study used a new formulation of the vaccine because changes were needed
for the scale up to manufacture the vaccine for phase 3. That is what I think doomed the phase 3 study.
So they ran a safety study on the new vaccine formulation and looked at survival too. However, it was
a single arm trial with 22 patients. Everything seemed okay. From the above paper:

Requirements necessary for large-scale production of the vaccine to
support a randomized phase III trial resulted in a change in vendor
for the monophosphoryl lipid A component of the vaccine formulation.
The source micro-organism for the lipid A remains the same, but
manufacturing differences result in subtle changes to the lipid A acyl
chain composition of L-BLP25. The primary objective of this study
was to evaluate the safety of this new formulation of L-BLP25 in
patients with unresectable stage IIIA or IIIB NSCLC. The secondary
objective was to report observed survival in this patient population.
Study Design
This was a single-arm, multicenter, open-label phase II study
(Study 305 [EMR 63325-006]) to assess the safety of L-BLP25 manufactured
with the immunoadjuvant monophosphoryl lipid A from
the Corixa Corporation in patients with unresectable stage IIIA or
IIIB NSCLC.

My guess is that some small change in the vaccine was enough to alter the immune response.
The new formulation may have increased survival but perhaps there was enough difference to
result in a smaller increase that was not significant.