Our History

The history of development Of OncoVAX: A personal immunotherapeutic Vaccine for preventing progression and cures in colon cancer.

The development of a cancer vaccine has some unique challenges.  Unlike the conditions associated with successful viral and bacterial vaccines, we have learned over the past 3 decades that cancer is a heterogeneous disease with multiple and rapid mutations. Thus there is genomic heterogeneity that limits any targeted therapeutic approach. The failure to achieve cures by the hundreds of cancer vaccines over the past 30 years was due to the lack of consideration of the genomic heterogeneity and a failure in patient selection. No tumor specific vaccines worked in late-stage disease.  It goes against the entire tenet of vaccinology. I will summarize with a scholarly quote from my good friend and colleague, the late Dr. I J Fidler, “The biologic heterogeneity of primary tumors and metastases presents with three implications to therapy.  First, targeted therapy requires a stable target.  Second heterogeneous disease cannot be treated by a homogeneous therapy.  Third, a chronic disease cannot be treated acutely.  Serious consideration of these principles should allow the design of better Immunotherapies for the fatal phase of cancer metastasis”

The development of OncoVAX for the treatment of minimal residual disease colon cancer spanned a period of 48 years. Along with a dedicated and talented staff of research and clinical associates, this basic and clinical research had many sponsors over that period, and they should be honored and credited with the beneficial clinical results of these studies.

The principal sponsor for the basic research in guinea pigs and the first clinical Phase I and II trials in humans were done under the auspices of the National Cancer Institute at the NCI/Frederick Cancer Research Center (FCRC), now known as the NIH/NCI National Laboratory. Dr. Hanna was the selected Director of Basic Research from 1974-1977 for a newly created program of investigator-initiated research under a government contract.  The history of NCI/Frederick was unique, and research in Immunotherapy of Cancer, which was out of the mainstream of cancer treatment, was allowed in the Basic Research Program. Dr. Hanna then was selected to be the Director of the entire center (1977-1983) and he had the responsibility to work with the NCI Director, Dr. Vincent DaVita to establish the NCI Biologic Response Modifier Program.  Under the auspices of this program, Dr. Hanna, in collaboration with Dr. H. Hoover, conducted the first Phase I clinical trial of OncoVAX at The Johns Hopkins Medical Center in Baltimore Md.  A major Phase II study of OncoVAX was conducted by the NCI through the Eastern Cooperative Oncology Group (ECOG) and the results validated that three vaccinations produced an immune response in the patients to their own tumors. This was the first demonstrated response that an immunized patient can be stimulated to mount a significant cellular immune response to its own (autologous) tumor. In other words, tumor specific immunity.

Dr. Hanna moved from the FCRC to Litton Bionetics, a company within Litton Industries in 1984.  He had his own facilities and laboratory to continue the development of OncoVAX. Litton Industries was a major government contractor which developed the Cruise Missiles and built many Destroyers for the Navy. The joke was that Litton supported Hanna’s work “in case peace broke out”. Well, peace did not break out resulting in Litton selling their entire medical division to a Dutch conglomerate, Akzo Nobel. The Litton Institute of Applied Biology was a major attraction of Akzo Nobel.  Knowing that a principal component of the Vaccine was an immunostimulant, TICE BCG, Dr. Hanna negotiated with the University of Illinois for an exclusive license for the BCG under the auspices of the business units Organon and Organon Teknika. and they supported the first Phase III trial of OncoVAX. This study was completed in 1999.  This trial capitalized on the findings of the NCI/ECOG study but added a booster fourth vaccination at 6 months after surgery.

Phase IIIA, ACTIVE, 8701 trial in colon cancer with second generation OncoVAX. This 254-patient study, which has allowed Vaccinogen to make efficacy claims for its current version of OncoVAX and is called the ACTIVE study by the company, had its results published in The Lancet in January 1999. In this study the investigators used 10⁷ BCG organisms for the first two doses and tumor cells alone in the third vaccination.  In addition, a booster vaccination of tumor cells alone was added at six months after surgery with 10⁷ irradiated autologous tumor cells. Over a median follow-up period of 5.3 years there was a 44% risk reduction for recurrence for patients that received OncoVAX (p=0.023), but only patients who had stage II disease benefited. For these patients the risk of recurrence was cut by 61%. The cost of the product was subsequently studied by medical technology assessment specialists at the Erasmus University Medical Center in Rotterdam who reported ‘impressive health economics benefits’ in a paper in Vaccine.  In 2012 the investigators revisited the data to see if there were different outcomes for patients with microsatellite unstable versus stable colon cancer. In the process they tracked event-free survival for the study population out to 15 years, finding a hazard ratio for the treatment group of 0.62 (p=0.033).

Also, during this clinical trial, Dr. Hanna became aware of the fact that many urologists had started using TICE BCG off label to treat Carcinoma in situ of the bladder. This cancer was being treated marginally with chemotherapy but the treatment with BCG produced 75% complete responses.  Dr. Hanna filed a retrospective study with the FDA and gained approval.  He also started a clinical trial with NCI/Southwest Oncology Group (SWOG) and demonstrated a significant prevention of disease progression and elimination of the recurrence of the tumor.  TICE BCG gained FDA approval for this form of bladder cancer, as well.  Akzo Nobel, sold its medical group, in 2000.  They gave Dr. Hanna his laboratory building and abundant startup funds to maintain his research and staff.  When the Phase III OncoVAX data was presented to the FDA in 2003, Hanna was presented with numerous manufacturing challenges from CIBR of the FDA.  These included sterility issues, automated potency and identity tests, manufacturing facility requirements and many more.  All these corrections were met to the satisfaction of the FDA and supported by impressive clinical bioequivalence testing.

In 2015 FDA granted a pivotal Phase IIIB clinical trial with a Special Protocol Assessment, fast an interim analysis and fast track review.  Thus, Vaccinogen was charged with the conduct of the pivotal FDA granted Phase IIIB trial, along with the registration and marketing for the product. The company’s research manufacturing facility in The Netherlands, which supported the Phase IIIA clinical trial, was no longer practical for the licensed product.

During this period, the company was depleted of capital and while on the over-the-counter public market, was delisted for failing to meet filing and economic requirements.  Despite the economic crisis the company obtained another major asset, a new patent “Autologous Cancer Vaccines and Methods’ Patent number 11351235 with exclusivity to 2039.  This patent not only claims the new FDA manufacturing requirements but also offers a safe and accurate method to increase the tumor volume, if necessary, per patient.  This procedure would double the accessible Stage II colon cancer patients for OncoVAX treatment.

The company now has two major assets, the exclusivity of the clinically tested manufacturing procedures and the low risk, OncoVAX Phase IIIB pivotal trial.  Vaccinogen is ready to finish the development of this unmet medical need for the third or fourth major cause of death from cancer.   The company desires to complete this effort with a pharma company partnership or new investors. It is interesting to note that the need for this cancer treatment process has increased, over the last years the diagnosed colon cancer in patients under the age of 50 years has been increasing around the world.  In our published first phase IIIA clinical trial, over 25 years ago the mean age was 65.  There are a variety of explanations for this change, but none are absolute.  The need for OncoVAX is however, absolute.