In man's continuing war against disease he has declared victory against many bacteria, viruses, genetic mutations, injuries and developmental abnormalities. In most cases the foe is destroyed, beaten into submission, corrected or its complications treated in such a manner as to increase the victim's standard of living to an acceptable level. We now battle a formidable foe gaining in strength and numbers as time progresses with the healthcare and pharmaceutical sectors having made good headway in some areas while failing miserably in others. This enemy is intelligent enough to use the victim's own body to wage war on itself and even "tricks" the body into thinking the disease needs additional blood supply and nutrients to grow and spread. It is also crafty enough in its camouflage to virtually be ignored by the body's immunity system as it wages its attacks.
2012 will witness cancer adding about 1.6 million sufferers in the United States with about 570,000 dying from any of many forms of the disease or its complications. Even more alarming is the 2010 prediction by the World Health Organization (WHO) that by 2030 more than 21 million annual cases of cancer will be diagnosed annually in the world with a mortality of 13 million cases annually. Advances have been made in resection (surgery), radiotherapy and chemotherapy treatments with good success in many cancers in removing or destroying cancer and sending it into remission. In many cases this remission may last a lifetime while others may only benefit from weeks, months or a few years before recurrence. However, surviving cancer or cancer stem cells, external/environmental or genetic factors or other catalysts often trigger recurrent battles with the disease. In many cases these subsequent battles are often more difficult as the cancer "learns" how to fight back and is often resistant to the chemotherapy or other agents that beat back the first generation.
A new generation of cancer drugs that uses the body's immunity system rather than compromising it is in its infancy and is termed the immunotherapy approach. There are currently several mechanisms by which these immunotherapy drugs work ranging from biolipid pathway regulation, cancer vaccination and growth factor regulation among many others. The first major success by a pharmaceutical with this approach was the 2010 FDA approval for the cancer vaccine, Provenge, produced by Dendreon Corporation (NASDAQ:DNDN). Provenge was approved for men with metastatic castration-resistant prostate cancer, for whom hormone suppressant therapy has not worked. Although argument has been made that its price tag of more than $90K for its treatment course is expensive for a drug that typically adds "only" 4-5 months to the victims' survival, the victims themselves will likely not interpret 4-5 months of additional life as "only." Once marketed, the drug did not see the expected sales upfront for many reasons in addition to the cost, however recent updates indicate that the sales are picking up and the company's share price has benefited accordingly. 3Q 2011 sales were roughly $66 million with the 4Q sales jumping to over $80 million as the company stated that the drug was gaining more popularity with doctors and there was more clarity as to how insurance was going to reimburse the healthcare providers for the upfront costs they initially had to incur.
2012 could be a significant year for the immunotherapy approach to fighting cancer with key data due in many clinicals. Provenge's approval was huge in that it was not only the first cancer vaccine approval but also the first immunotherapy approval for cancer. Bigger immunotherapy drug approvals for more widespread cancers with more blockbuster potential could be coming soon, benefiting shareholders and more importantly the victims and healthcare providers needing better weapons in their arsenal against the disease. There are three biotech companies of interest developing cancer vaccines for differing indications and at multiples stages of development that will be reporting final or interim data in their cancer vaccine clinicals for 2012. If Provenge represents the legitimization of the immunotherapy approach and its regulatory approvability, then these companies' upcoming trial data could indicate the blockbuster potential that this group of drugs could represent. Their potential, and the share price action accompanying them depending on company market capitalizations, warrant a thorough look by potential shareholders, Big Pharma suitors, healthcare providers and patients alike.
The lung cancer vaccine, Stimuvax, has additional potential in applications for cancers of the lungs, breast, colon, ovaries and pancreas.
Oncothyreon Inc. (ONTY) is a biotech company focused on attacking cancer through small molecule and synthetic vaccines. Their lead product is the lung cancer vaccine Stimuvax, an innovative vaccine designed to cause an immune response to cancer cells expressing MUC1. MUC1 is a type of antigen called a mucin, which lines the apical surface of epithelial cells in the lungs, stomach, intestines, eyes and several other organs. Its overexpression is implicated in many cancers of the lungs, breast, colon, ovaries and pancreas. Cancer vaccines must have a target or a means by which to differentiate cancer cells from normal healthy cells in order to have the desired specificity. MUC1 is the "target" for Stimuvax.
Merck KGaA (OTCPK:MKGAF) is currently developing Stimuvax under a licensing agreement with Oncothyreon. They have two pivotal phase III trials for NSCLC (Non-Small Cell Lung Cancer) the larger of which is the START (Stimulating Targeted Antigenic Responses To NSCLC). Merck KGaA is likely to report interim data soon triggered by a pre-determined number of patient deaths. The trial is designed to test the vaccine's efficacy in increasing survival by at least 6 months in newly diagnosed patients with tumors confined to the chest area but are not candidates for resection. Stimuvax is given after the standard of care treatment of chemotherapy and/or radiation and is intended to jumpstart the immunity system and teaches it to attack any newly formed or residual cancer cells with the MUC1 overexpression. The trial enrolled 1,514 patients and time is winding down to this catalyst, which will possibly be a good indicator of whether or not Oncothyreon could receive the $90 million in milestone payments from Merck KGaA upon regulatory approval. Royalty payments are rumored to be in the mid teens for North American sales and high single digits for the rest of the world, an impressive amount for a company with a market capitalization currently under $270 million.
In a January 11th article, Oncothyreon's CEO states his optimism on Stimuvax saying that the longer it takes the interim data to be reported out the better as this would be an indication of the drug's effectiveness in NSCLC. He also noted that human trials using the Oncothyreon's wholly owned ONT-10 will initiate in 1Q, and the Stimuvax results could validate its approach in attacking cancer even as that trial begins. Stimuvax's other phase III trial, termed the INSPIRE trial for Asian patients with advanced NSCLC, is nearly identical to the START trial with the same interim data analysis assumed. If data on these trials is favorable and indicate the trials should resume, the immunotherapy approach in attacking at least NSCLC could be validated and possible success in other cancers with the overexpression of the MUC1 antigen could be assumed. If the START trial, which is presumed to report interim data first, is determined to go to completion, top line data will likely follow in 2H 2012. Data could be released any day for the START patient set, and the anticipation will only grow as the longer the trial runs the better the drug is apparently working for this patient set. Success here will likely trigger increased investor and Big Pharma interest throughout the immunotherapy drug sector while failure could cause many to step back and reevaluate their investment's potential.
NeuVax has huge market potential possible for this $29.1 million market cap company with indications for adjuvant after-surgery treatment of early-stage HER2/neu-expressing breast and prostate cancer as well as other types of solid tumors.
Galena Biopharma (NASDAQ:GALE) presented 5-year phase II data from its NeuVax immunotherapy drug to combat breast cancer in December 2011. The data set the stage for what could be an exciting 2012 for this microcap biotech. NeuVax works by binding the tumor-associated peptide, E75, to the HLA-A2 and HLA-A3 molecules on the surface of tumor cells and Antigen Presenting Cells. E75 binds to the HLA-peptide-T-cell receptor complex sending out a signal to circulating T-cells that would then recognize the HER2 (human epidermal growth factor receptor 2)- expressing tumor cells as "invaders". T-cells begin targeting the cells that before were invisible to the human immunity system and were actually thriving in the system it had tricked into providing them with blood and nutrients to grow and proliferate. Additionally, activation of these T-cells leads to clonal expansion and proliferation of E75-specific T-cells that circulate throughout the system and identify and attack cancer cells over-expressing HER2. This self-replicating means that the amount injected will give exponentially increasing efficacy as the levels of the "educated" T-cells increase.
The phase II trial did determine a key factor that will be invaluable in the phase III trial. For the entire population set in the patients receiving NeuVax, a strong association to prevention of recurrence was observed with the vaccine treated patients demonstrating a disease-free survival rate of 89.4% versus 79.7% in the control group (p = 0.098). However, waning efficacy was noted in the patient set sometime after the drug treatment protocol had completed. 53 patients were administered at least one booster inoculation (once every six months) with a dramatic increase in efficacy as evident in statistically significant disease-free survival rate of 95.9% versus 79.7% in the control group (p = 0.016). With radiotherapy and most chemotherapy drugs, this would have added to the safety concerns associated with the additional dosages meaning additional toxicity. However, as evident in many if not most immunotherapy drugs in mid and late-stage testing, the safety profile of the drugs is such that the additional doses didn't appear to compromise the safety profile.
A SPA (Special Protocol Assessment) trial design has been granted to the NeuVax phase 3 trial (termed the PRESENT trial for Prevention of Recurrence in Early-Stage, Node-Positive Breast Cancer with Low to Intermediate HER2 Expression with NeuVax Treatment) by the FDA. This SPA designation gives the company better guidance and a more clearly defined set of goals in order to determine if the phase III data will be acceptable to support regulatory approval of NeuVax. This trial design will certainly come into play as intermediate data of the trial is released from this trial, which commenced January 20th of this year. Due to the nature of the drug's specificity, the NeuVax Phase 3 trial will be conducted in adjuvant breast cancer patients who are node positive (cancer cells have been found in the lymph nodes), have an HLA status of A2/A3+, and have low or intermediate HER2 expression (IHC 1+, 2+, often referred to as HER2 negative).
The patients in the trial would have already completed the standard of care treatments of resection (surgery) and/or radiotherapy chemotherapy and have had a complete response from those treatments. The approximately 700 patient set will be randomized with part of the patients receiving NeuVax and part receiving the control. Patients will receive one injection every month for six months, followed by a booster inoculation every six months thereafter. The primary endpoint is disease-free survival at three years or 139 events (cancer returns). A data safety monitoring board will conduct an interim analysis for safety and futility after 70 events. The press release also noted that Galena is on track for the initiation of approximately 100 investigator sites in the U.S. and abroad, a large number needing only an average of 7 patients per site to track in order to complete enrollment in the trial. Any updates on this now-enrolling PRESENT trial along with additional data from the ongoing phase II trial will be key catalysts for this microcap biotech for 2012.
Allovectin's mechanisms are applicable to any type of accessible, immunoreactive solid tumors, providing multiple follow-on indications, such as prostate cancer, breast cancer, and head and neck cancers.
Vical Incorporated (NASDAQ:VICL) started 2011 off with more-clearly portrayed phase II data in their Allovectin-7 trial for patients with metastatic melanoma. The most recently completed Phase 2 trial was a single-arm, open-label study in which 127 chemo-refractory or chemo-intolerant subjects were treated with Allovectin-7. There were no treatment-related Grade 3 or 4 adverse effects and no withdrawals from the trial due to patient intolerability. The overall response rate for the 127 patients receiving the high-dose treatment was 11.8%, with 4 complete responders and 11 partial responders. The median duration of response was about 14 months and median survival was nearly 19 months. These data compared favorably against historical controls from other studies in metastatic melanoma and helped provide guidance for the FDA's SPA in their phase III trial.
Allovectin-7 works by stimulating an immunity response by T lymphocytes (T Cells) to attack tumor cells expressing HLA B7/β2M. The drug not only tentatively destroys the tumor it is injected into via allogeneic anti-tumor response, but it also restores tumor-associated antigen presentation via MHC class 1 and boosts the immune response by the lipid/DNA-induced danger signal (most chemotherapy and radiotherapy actually compromise the patient's immunity system causing additional problems later on). These danger signals are surmised to act by stimulating dendritic cells to mature so that they can present foreign antigens and stimulate T lymphocytes to begin their work at killing the cells. This multi-faceted approach is fairly unique in the immunotherapy drug world in that it is a first-line attack intended to act alone rather than to "clean up" the residual cancer cells left over from or developing after other standards of care have been performed.
The Phase 3 trial, which started in January 2007, is evaluating Allovectin-7 as a first-line therapy in patients with Stage III or IV recurrent metastatic melanoma. Vical completed enrollment in February 2010 of approximately 390 chemo-naive patients randomized on a 2:1 basis: about 260 for treatment with Allovectin-7 and approximately 130 for treatment with either dacarbazine or temozolomide (current standard of care drugs). The trial protocol allows a maximum two-year treatment and follow-up period for the primary endpoint (response rate at 24 weeks or more after randomization), so the last patients must complete treatment by February 2012. Top-line data for the primary endpoint and secondary endpoint (overall survival) should be in Q2 and will be a significant catalyst for the company, whether positive or negative. This is a pivotal trial and its potential success can lead directly to a drug application and potential regulatory approval. Not only would the latter provide the company with much needed revenue, it could also validate the drug's approach in attacking many forms of cancer with similar HLA B7/β2M expression making this a huge catalyst for this $245 million market cap biotech.
In each of these three biotechs, investors must realize and more fully understand the potential marketability of the drugs and platforms. The data coming due in 2012 for each of these drugs could potentially legitimize (or otherwise) not only the drugs' intended indications but also their applications for multiple other indications. With an understanding of this as well as additional research into each company's financials and pipeline depth potential, investors will be able to ascertain the upside potential and downside risk for each. Investors' opinions and interpretations will drive the share price for each into oversold and overbought conditions rapidly depending on the data presented and their interpretation by first the investors and then analysts. Trade and invest wisely, intelligently and unemotionally not since this is the biotech sector, but especially since this is the biotech sector.
Disclosure: I have no positions in any stocks mentioned, but may initiate a long position in VICL over the next 72 hours.