Galena On Track to Advance NeuVax
By Grant Zeng, CFA
Final Results of NeuVax Phase I/II Trials Presented at
the 35th Annual CTRC-AACR San Antonio Breast Cancer
On December 7, 2012,
Galena Biopharma (
presented data from the completed SN-33 trial and final results
from the Phase I/II trials of NeuVax (nelipepimut-S or E75) for
breast cancer at the 35th Annual CTRC-AACR San Antonio
Breast Cancer Symposium.
To download a free copy of our most recent report on GALE, please
Overview of the Phase I/II Trails
The Phase I/II trials of NeuVax included SN-33 (Node Positive,
n=97) and SN-34 (Node Negative, n=90), which evaluated a combined
187 patients with 108 in the vaccine group (VG) and 79 in the
unvaccinated control group (CG).
In terms of patient demographics, we think the vaccine and
control groups were generally well-matched. Although there were
some imbalances between VG and CG, they were not significant. The
only statistically significant difference was ER-/PR- status
(31.1% in VG vs 17.7% in CG, p=0.04).
The Rational for Booster Inoculation
Patients were initially given a series of up to six
inoculations of NeuVax once a month. As the trials progressed,
the physicians noticed that E75-specific immunity waned after
this initial monthly primary vaccine series (PVS) and translated
to late recurrences of cancer in some patients. As a result of
this finding, a voluntary booster program was added to the trials
to maintain long-term immunity following the initial monthly
The booster program offered patients an additional inoculation
every six months with a maximum of six boosters. Because the
booster program was voluntary, not all women chose to receive the
full six additional doses.
The Combined SN-33 and SN-34 Results
Trials SN-33 (NP) (n=97) and SN-34 (NN) (n=90) enrolled
clinically eligible patients who were rendered disease-free after
completion of standard of care multi-modality therapy (n=187).
Treatment assignment was then based on HLA type, with HLA-A2/A3
patients vaccinated and HLA-A2/A3 negative patients followed
prospectively as controls for recurrence. NeuVax exhibited an
excellent safety and tolerability profile, and demonstrated a
durable response out to 60 months:
- Maximum toxicity for all inoculations produced primarily
Grade 1 and some Grade 2 toxicities, with injection site
reactions and fatigue most common. No serious adverse events
(SAEs) or cardiotoxicity were reported.
- At 24-month: 94.3% of NeuVax patients were disease-free
versus 86.8% of patients on the control arm (p=0.08).
- At 60-month: 89.7% of NeuVax patients remain disease-free
versus 80.3% of patients on the control arm (p=0.077)--a
recurrence reduction of 47.7% among all patients at any dose.
Multiple dose response analyses underscore the efficacy of the
vaccine with statistical significance being achieved among the
optimally-dosed and boosted patients.
The SN-33 HER2 Negative Booster Results
SN-33 was conducted in node positive patients, and was well
balanced between the two arms: Vaccine HLA-A2/A3 positive (n=53)
vs Control HLA-A2/A3 negative (n=44). During the conduct of
this trial, Herceptin® (trastuzumab; Genentech/Roche) became
commercially available for HER2 IHC Positive (3+) patients, and
the trial was modified accordingly to allow these patients to
receive Herceptin, and exclude this patient group from future
enrollment and analysis.
Below are the summary results from the SN-33 trial. SN-33
Intent-to-treat (ITT) population (n=97); NeuVax (n=53) vs.
- At 24-month: 90.6% of NeuVax patients (n=53) were
disease-free versus 79.5% of patients on the control arm (n=44)
- At 60-month: 84.7% of NeuVax patients (n=53) remain
disease-free versus 77.1% of patients on the control arm
SN-33 HER2 Negative IHC 1+/2+ patients who received
(n=45). NeuVax (n=18) vs. Control (n=27).
- At 24-month: 0% recurrences for patients treated with
NeuVax: statistically significant DFS for NeuVax at 100% vs.
77.8% Control (p=0.0358).
- At 36-month: 0% recurrences for patients treated with
NeuVax for a statistically significant DFS for NeuVax at 100%
vs. 77.8% Control (p=0.035). Of note, no patients receiving
booster inoculations had a recurrence through 36 months, which
is the Phase III PRESENT study endpoint.
- At 60-month: 5.6% recurrence rate with NeuVax versus 25.9%
recurrence rate in the control arm. DFS for NeuVax at 94.4% vs.
74.1% Control--a recurrence reduction of 78.4% in the target
This new, 60-month data analysis shows that breast cancer
recurrence is greatly reduced for patients treated with NeuVax
and that these results are both clinically relevant and durable
of the booster inoculations from the data presented: the booster
inoculations are well-tolerated and don't increase any side
effects compared to the primary vaccine series. Further, booster
inoculations appear to assist in the maintenance of long-term
peptide-specific immunity. In terms of efficacy, boosted patients
have better recurrence rates and improved DFS compared to
patients who did not receive vaccine. This may be attributed to
increased immunity induced by the booster inoculations.
As a result of these findings, booster inoculations have been
incorporated into the design of the ongoing Phase III PRESENT
The Phase III PRESENT Trial is Underway
Based on the SN-33 booster data, on Jan. 20, 2012,
trial for NeuVax (E75 peptide plus GM-CSF) vaccine in HER2 1+ and
2+ breast cancer patients in the adjuvant setting to
The PRESENT (
tage, Node-Positive Breast Cancer with Low to Intermediate HER2
reatment) study is a randomized, multicenter, multinational
clinical trial that will enroll approximately 700 breast cancer
patients. The trial design has been updated to include current
National Comprehensive Cancer Network guidelines and recently
Special Protocol Assessment (SPA)
concurrence from the FDA. Based on a successful Phase II trial,
which achieved its primary endpoint of disease-free survival
(DFS), the FDA has agreed that the design and planned analysis of
the Phase III study adequately address the objectives necessary
to support an acceptable regulatory submission for marketing
The NeuVax Phase III trial will be conducted in adjuvant
breast cancer patients who are node positive, have an HLA status
of A2/A3+, and have low or intermediate HER2 expression (IHC 1+,
2+, sometimes referred to as HER2 negative). These patients are
not eligible to receive Herceptin (trastuzumab, marketed by
Roche-Genentech) therapy that is currently approved only for
patients with high HER2, or 3+ expression.
According to the protocol, once qualified patients have
achieved a complete response from current standard-of-care
treatment (surgery, radiation and/or chemotherapy), they will be
randomized and dosed with either NeuVax (E75 + GM-CSF) or control
(placebo plus GM-CSF). Patients will receive one intradermal
injection every month for six months, followed by a booster
inoculation every six months thereafter.
The primary endpoint is disease-free survival at three
or 139 events (recurrence of cancer). A data safety monitoring
board will conduct an interim analysis for safety and futility
after 70 events.
To date, 70 sites are approved globally, with continued
expansion to over 100 sites planned.
We think the Phase III trial design is prudent based on the
existing data from the Phase I/II trials. This Phase III trial is
well designed and better controlled one compared to the Phase
We believe NeuVax has a blockbuster potential if it finally
reaches the market.
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