A Relatively Strong Pipeline
Galena Biopharma (NASDAQ:GALE) is a late stage biotechnology company focused on the discovery, development and commercialization of cancer immunotherapeutics. The company holds two proprietary drug discovery platform technologies: peptide-based immunotherapy and FBP targeted cancer vaccine.
Galena’s lead product candidate for cancer immunotherapy is NeuVax, which is a peptide-based immunotherapy to reduce the recurrence of breast cancer in node-positive, low-to-intermediate HER2-positive breast cancer patients not eligible for Herceptin.
Galena Biopharma recently licensed worldwide rights to develop and commercialize a Folate Binding Protein-E39 (FBP) targeted vaccine to prevent recurrence in gynecological cancers such as ovarian and endometrial adenocarcinomas. The FBP vaccine was licensed from The University of Texas M D Anderson Cancer Center and Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc. (HJF).
Pivotal Phase III Trial will be Initiated in 1H2012 for NeuVax
On September 12, 2011, Galena announced a clinical trial update on its lead program, NeuVax (E75 peptide vaccine with GM-CSF adjuvant), a cancer immunotherapy targeted for low-to-intermediate HER2 expressing breast cancer patients not eligible for trastuzamab (Herceptin).
Galena received official notification from the U.S. Food and Drug Administration (FDA) that the Chemistry, Manufacturing, and Controls (CMC) partial clinical hold has been lifted. Galena has satisfied all requirements specified by the FDA and has initiated a clinical trial material manufacturing plan to remain on schedule to meet the planned trial start date.
- The CMC partial clinical hold has been lifted by the FDA, allowing the pivotal Phase 3 trial to commence.
- Galena has assigned a principal investigator and initial IRB approvals received--going to 100 trial sites in the US, Canada, and Europe.
- CRO Aptiv Solutions has been engaged and international trial operations are underway for the initiation of the Phase 3 PRESENT study in the first half of 2012.
Along with the clinical trial hold lift, Galena has made other significant developments in preparation for the Phase III trial initiation:
- Dr. Beth Mittendorf, Assistant Professor, Department of Surgical Oncology, University of Texas M. D. Anderson Cancer Center, has been selected as a principal investigator for the trial.
- Conditional Institutional Review Board (IRB) approval from two key trial sites has been received to allow for initiation of the trial, with additional worldwide sites expected to open shortly. It is anticipated that the trial will encompass approximately 100 trial sites in the U.S., Canada, and Europe.
- Galena has engaged the Clinical Research Organization (CRO) Aptiv Solutions to manage the trial and clinical operations are on track for PRESENT to commence in the first half of next year.
Galena plans to initiate Phase III PRESENT (Prevention of Recurrence in Early-Stage, Node-Positive Breast Cancer with Low to Intermediate HER2 Expression with NeuVax Treatment) study in the first half of 2012 under a Special Protocol Assessment (SPA).
Positive NeuVax Phase II Results Reported After 36 Months of Follow-Up
On June 6, 2011, Galena Biopharma announced updated data from its Phase II clinical trial of NeuVax™ at the American Society of Clinical Oncology (OTC:ASCO) annual meeting.
Galena is developing NeuVax for the adjuvant treatment of low to intermediate HER2 expressing breast cancer. The NeuVax Phase II trials enrolled 182 patients, including node positive and node negative, HER2 1+, 2+ and 3+ patients. All patients received standard of care (SoC) therapy and were confirmed to be disease-free prior to enrollment. Following enrollment, eligible patients were administered the NeuVax vaccine once a month for six months, followed by booster shots one every 6 months thereafter. The efficacy endpoint for the trial was disease free survival (DFS).
Key highlights from the Phase II trial include:
- Statistically significant increase in disease free survival at 36 months in the NeuVax treated group vs. the control group for the planned Phase III patient population (p=0.035). The vaccine treated group showed no recurrences of cancer (0% recurrence rate), while the control group demonstrated a 22% recurrence rate which is consistent with historical norms. The planned Phase III patient population as defined in the FDA approved Special Protocol Assessment includes breast cancer patients who are node positive, have low to intermediate HER2 expression (HER2 1+ and 2+ by IHC), are HLA A2+ & A3+ and who are disease free following standard of care therapy.
- An excellent safety profile, with no serious adverse events related to drug reported to date. All adverse events reported were minor and resolved within 24 hours.
- In the ITT (intent to treat) population who received all ranges of doses and schedules, the low to intermediate HER2 expressers continued to show significant activity in improvement of DFS (p=0.045), with the vaccine group demonstrating a reduction of 66% in relative risk for recurrence. This data demonstrates strong support for targeting of low to intermediate HER2 expressers, a group for which there is currently no HER2 directed therapies.
- The optimally dosed (1 milligram of E75 plus 250 micrograms of GM-CSF) group continues to demonstrate superior efficacy compared to sub-optimal doses (varying doses from 100 – 500 micrograms E75 plus 125 – 500 micrograms GM-CSF), with a recurrence rate of 3% for the optimally dosed group vs. 12% for the sub-optimally dosed group and 14% for the control group.
The above 36-monthy follow-up data are very encouraging, which underscore the potential for cancer immunotherapy to develop into potent and well tolerated targeted therapies. The positive results are the basis for the planned Phase III PRESENT trial.
Positive Results from Combination of NeuVax and Trastuzumab May Expand NeuVax Indication
On June 8, 2011, Galena presented Phase II efficacy results for NeuVax™ in combination with trastuzumab (Herceptin®; Genentech/Roche) at the ASCO annual meeting.
Data from two combination Phase II breast cancer trials were analyzed. One combination trial is NeuVax (E75) + Tz (trastuzumab); another combination trial is Vaccine X + Tz. Vaccine X is also a HER2-derived vaccine. A total of 283 patients have enrolled in the two trials (E75=187, Vaccine X=96). Overall median length of follow-up is 48 months (E75=57 months, Vaccine X=19 months).
Of 187 patients enrolled in the E75 trial, 108 patients were vaccinated with E75 + GM-CSF; 79 patients were in the control arm. Of the 187 total patients, 15 (8%) received adjuvant Tz therapy (the E75 trial was primarily conducted prior to the widespread acceptance of Tz as standard of care adjuvant therapy for HER2-overexpressing breast cancer).
In the Vaccine X trial, 41 patients were vaccinated with Vaccine X + GM-CSF while 55 patients were given GM-CSF alone (control arm). Of these 96 patients, 47 (49%) received adjuvant Tz therapy.
Of the patients who received adjuvant Tz treatment, 32 received no vaccine, and their recurrence rate is 12.5% (4/32)—comparable with reported rates of similarly staged and treated patients. In contrast, 30 patients received either E75 + GM-CSF (12) or Vaccine X + GM-CSF (18) after completing adjuvant Tz, with a recurrence rate of 0% (0/30) (p=0.064).
These preliminary results indicate the potential for NeuVax combined with Tz therapy for the improved treatment for HER2 3+ breast cancer patients. The data may provide another indication for NeuVax in the treatment of HER2 3+ breast cancer patients. Combination of NeuVax and trastuzumab represents a potential expansion of the market for NeuVax to HER2 3+ breast cancer patients in the adjuvant setting.
A Phase II Combination Trial is Planned in 1H12
Based on the preliminary positive results, GALE plans to initiate a Phase II trial in the 1H2012. The FDA has approved the trial in January 2012.
The planned Phase II trial is being funded by Galena Biopharma and Genentech/Roche through the Henry M. Jackson Foundation. Each company will provide their respective drugs for the 300 patient trial and approximately half of the funding necessary to complete the trial. The trial will be conducted at twenty sites worldwide and is expected to commence in the first half of 2012.
This trial will enroll 300 breast cancer patients with HER2 low-expressing tumors in order to establish the benefit of the combination versus trastuzumab alone in the adjuvant setting.
The study will be a multi-center, prospective, randomized, single-blinded Phase II trial evaluating NeuVax + trastuzumab (vaccine) vs. trastuzumab + GM-CSF (control) alone in the adjuvant setting in breast cancer patients. HLA-A2/A3+ node positive (or node negative if also negative for both ER and PR) breast cancer patients with HER2 1+ or 2+ expressing tumors who are disease-free after completing standard adjuvant therapies will be enrolled and randomized. Patients must have adequate cardiac function for enrollment (LVEF >50%), and randomization will be further stratified based on HER2 status (1+ or 2+) and nodal status (N0, N1, N2, or N3).
Galena Licenses Novel, Targeted Cancer Vaccine for Gynecological Cancers
Galena Biopharma recently licensed worldwide rights to develop and commercialize a Folate Binding Protein-E39 targeted vaccine to prevent recurrence in gynecological cancers such as ovarian and endometrial adenocarcinomas. The FBP vaccine was licensed from The University of Texas M D Anderson Cancer Center and Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc. (HJF).
FBP has been granted Investigational New Drug (IND) by the FDA to enter clinical trials. Institutional Review Board approval has also been received. Galena plans to initiate Phase I trials by the end of 2011.
The FBP vaccine consists of the E39 peptide combined with the immune adjuvant granulocyte macrophage colony stimulating factor (GM-CSF). FBP is over-expressed (20-80 fold) in more than 90% of ovarian and aggressive endometrial cancers, as well as 20-50% of breast, lung, colorectal, and renal cell carcinomas. FBP has very limited tissue distribution and expression in non-malignant tissue and has many years of validation as an ideal immunotherapy target.
The broad overexpression of FBP in a wide variety of cancers indicates that FBP vaccine has a potential targeting multiple cancer indications.
The market for FBP vaccine is huge. Ovarian cancer occurs in over 22,000 patients per year in the U.S. alone and is the most lethal gynecologic cancer. Endometrial cancer is the most common gynecologic cancer and occurs in over 43,000 women in the U.S. annually. If developed successfully, FBP vaccine could be an important option for physicians to target ovarian and endometrial cancers.
We think the acquisition is positive to Galena. The license of FBP vaccine further enhance Galena's oncology pipeline.
What do All These Mean for GALE?
Apparently, Galena has made great progress in the past few months for its clinical programs while balance sheet has been boosted. The company has become stronger than ever now than before with more focused cancer programs and less cash burn for its operations.
Galena’s cancer program NeuVax and FBP provide significant leverage in cancer immunotherapy generally, as well as in "off the shelf" vaccines.
The company recently enhanced the NeuVax patent portfolio by acquiring patent rights covering the use of NeuVax in combination with trastuzumab (Herceptin); and use in low-to-intermediate HER2+ breast cancer patients not eligible for Herceptin therapy. The company also removed the CMC hold for NeuVax. NeuVax Phase I/II clinical trial results was cited in the journal Cancer, published by the American Cancer Society. Positive data from the Phase II NeuVax clinical trials was presented at the 26th Annual Meeting of the Society for the Immunotherapy of Cancer, which demonstrated that patients with less aggressive disease traits may derive greater clinical benefit from vaccination and have lower rates of breast cancer recurrence. The addition of FBP further expanded the company’s focused cancer pipeline.
We are certainly impressed by the progress Galena has made recently which has demonstrated the company’s commitment to maximizing shareholder value. Gale is moving in the right direction. The company is poised for long term growth and creating shareholder value in my view.