The commercial potential of a cancer therapy not only depends on its efficacy and safety profile but also how many different cancers it can be used to treat. Huge amounts of money and time are spent developing cancer drugs, and if one is able to treat multiple indications due to its design, the return on investment could be substantial. The current king of multiple indications is Genentech's Avastin (bevacizumab), a single therapy that is used to treat multiple cancers. This anti-VEGF antibody is approved to treat four different cancers including colorectal, lung, renal, and brain along with off-label uses such as wet AMD and breast cancer. Sales of this blockbuster drug are expected to peak at $7.5 billion worldwide. Herceptin (trastuzumab), an anti-HER2/neu antibody also from Genentech, is approved for both breast and gastric cancers and has peak sales forecasts of about $6 billion worldwide.
In order to remain competitive and even profitable, it is critical for oncology companies to be able to expand the number of therapeutic indications to maximize the market potential of their products. Many companies often have several trials in different cancer indications for one product running simultaneously. This crossover can be beneficial as the safety profiles are most important in the earliest clinical trials and a safe profile for one indication means less work could be required to prove safety for additional indications.
For individual and institutional investors, it is often important to understand the scientific underpinnings that go into the rationale behind the pursuit of each type of cancer a company chooses to undertake with their therapies. Cancer cells have unique features that distinguish themselves from normal cells in the body. Tumor-associated antigens (TAAs) are markers (typically proteins) present either in only cancer cells or in much higher concentration in cancer cells than in normal cells. Thus, many therapies target TAAs as a mechanism to attack cancers. HER2/neu, for example, is a well-known TAA that has been found on breast, ovarian, and colon cancers. Therefore, a drug targeting HER2/neu may serve the purpose of treating these three indications and possibly more.
Several companies mentioned below are attempting to use immunotherapy agents to target TAAs. Unlike conventional cancer drugs which directly attack cancers, cancer immunotherapies stimulate patients' immune systems to inhibit cancer growth. Activating the patients' immune systems to target TAAs is highly specific, typically durable, and usually much less toxic than conventional cancer therapies. Not only are the conventional chemotherapy drugs in use cytotoxic, but they also weaken the patients' immunity systems muting their own immune responses and making all of the cancer fight dependent on the toxic drug and not allowing to body to defend itself. Additionally, the subjects are more susceptible to secondary infections by viruses or bacteria during their weakened states.
Andrew Norris recently wrote an informative Seeking Alpha article summarizing the benefits of targeting multiple TAAs from a clinical standpoint. It is important to note that immunotherapies that cover a broad range of TAAs or specific TAAs that are found on a variety of different cancers have the potential to be used in many different cancer indications. The marketing potential for these types of drugs is phenomenal. From an investor's standpoint, the upside potential in an early-stage biotech developing a drug with such a range of TAAs could be very lucrative. As the drug progresses through early clinicals and proves its safety and efficacy profiles, the upside would quickly become clear with a tremendous run up in common stock price, company market capitalization and therefore company price tag (for acquisition purposes). Following is a summary of several biotechs and pharmaceuticals with immunotherapy drugs at varying stages of development. For those drugs approved already for certain indications, the upside for investors is certainly still there with a more stable and revenue-generating company there to avert some risk. However, for those biotechs in early stage development showing signs of success with favorable safety and efficacy data behind them, the upside coming could be substantial with the higher accompanying risk for failure otherwise. Early success in one indication would quickly legitimize the drug for other indications expressing the same TAAs. One doesn't have to be a biotech analyst to understand what that would potentially mean for the company's common stock price as well as the company price tag.
Dendreon's (NASDAQ:DNDN) Provenge (sipuleucel-T) was the first cancer immunotherapy to receive FDA approval in 2010 for the treatment of prostate cancer. Provenge targets prostatic acid phosphatase (PAP), a TAA commonly found on prostate cancer cells but not on other cells. Dendreon's second product currently in development is DN24-02, which targets HER2/neu, a TAA widely found on numerous cancers, including breast, ovarian, and colorectal. DN24-02 is currently in a Phase II trial for urothelial carcinoma and is still actively recruiting patients.
ImmunoCellular Therapeutics' (NYSEMKT:IMUC) lead product, ICT-107, is currently recruiting for a Phase II trial to treat newly diagnosed glioblastoma multiforme (GBM), a common form of brain cancer. Recruitment is ahead of schedule and is expected to complete in Q2, 2012. ICT-107 targets six TAAs including TRP-2, MAGE-1, HER-2, IL-13 receptor a2, gp100 and AIM-2. The Phase I data was extremely hopeful in which median overall survival for the patient set was 38.4 months with a median progression free survival of 17 months. The three-year OS for the patient set was 55% with 6 patients having no recurrence of the tumor after three years. With the current prognosis for GBM at about 3 months median OS with no treatment and about 15 months for those receiving current standard of care, the implications are profound. A second product, ICT-140, targets EphA2 which is involved in ovarian, breast, colorectal, prostate, and lung cancers, as well as aggressive melanomas as well as mesothelin, which is found in high concentrations on mesothelioma, in addition to ovarian and pancreatic cancers. Their third cancer vaccine, ICT-121, targets CD133, which is a marker for cancer stem cells, and can be potentially used as a universal cancer therapy. The company plans to initiate Phase I trials for ICT-140 and ICT-121 sometime this year. This company is a prime example of an early stage biotech with promising early clinicals primed to provide a substantial return on investment as the pipeline legitimizes itself for current as well as obvious future indications. Of special interest in the coming months will be catalysts such as ICT-107 Phase 2 enrollment completion and interim data analysis in Q4 2012 or Q1 2013.
Galena Biopharmaceuticals (NASDAQ:GALE) recently initiated a Phase III trial for NeuVax in treating breast cancer patients. Like Dendreon's and ImmunoCellular Therapeutics' cancer vaccines, NeuVax also targets the HER2/neu antigen. The upside in ImmunoCellular's ICT-107 is due to its orphan drug status for GBM along with its potential for multiple indications likely coming. However, Galena's NeuVax breast cancer indication has a huge upside right out the gate with the potential market being an indication in which almost 300,000 new cases are diagnosed every year. A 53 patient subset in the NeuVax Phase II trial that received a booster vaccination once every six months after the initial treatment protocol yielded a dramatic increase in efficacy as evident in a statistically significant disease-free survival rate of 95.9% versus 79.7% in the control group (p = 0.016). The Phase III trial is based on the same type of booster schedule and the company is hopeful that these pivotal results will be comparable. Their second cancer vaccine, FBP, which is in Phase I development, targets folate binding protein (FBP). FBP is found on 90% of ovarian and endometrial cancers as well as 20-50% of lung, breast, colon, and renal cancers. Galena's investment potential is due to an early huge marketing indication being possible with multiple other indications coming via NeuVax and FBP. The upcoming trial and regulatory updates should provide Galena investors multiple catalysts in the coming months.
Celldex Therapeutics' (NASDAQ:CLDX) lead product, rindopepimut, which targets EGFRvIII is currently in a Phase III trial in patients with newly diagnosed GBM and a Phase II trial in patients with recurrent GBM. EGFRvIII is expressed in about one third of GBM patients but also reported in lung, breast, ovarian, and prostate cancers. Rindopepimut was partnered with Pfizer earlier, but the rights were returned to Celldex for unspecified reasons. Celldex's deep pipeline includes another product, CDX-1401, in a Phase I/II trial for several cancers. CDX-1401 is an antibody targeting dendritic cells linked to the TAA, NY-ESO-1. This TAA is widely expressed on several tumors: approximately a quarter of all lung, prostate, melanoma, bladder, esophageal, and ovarian cancers.
Oncothyreon's (NASDAQ:ONTY) Stimuvax, which is partnered with Merck KGaA and in pivotal Phase III trials for non-small cell lung cancer, targets the antigen mucin 1 (MUC1). MUC1 is found on more than 90% of breast carcinomas and is also associated with colon, ovarian, pancreatic, as well as lung cancers. The Stimuvax trials were halted a few years ago due to a case of encephalitis observed in a separate study, but recent interim analysis showed that the Phase III trials should continue to completion. With the stock now trading at suppressed levels due to negative investor sentiment about the trial continuing on into 2013, Oncothyreon investors could see good upside to the stock in the coming months as the trial wraps up.
With the FDA approvals of Provenge and more recently, Bristol-Myers Squibb's (NYSE:BMY) Yervoy (ipilumumab), cancer immunotherapy has been validated as a legitimate treatment for cancer. There is sufficient scientific rationale that cancer immunotherapies can be developed for many indications. While it is still too early to determine whether or which cancer immunotherapies currently in development will eventually receive regulatory approval, investors should not underestimate the value of these assets as a platform to treat multiple cancers. The success of the Provenge and Yervoy drugs will likely only be the beginning as the technology is becoming more robust, more antigens are being discovered, the drug manufacturing process is being more fully perfected, and individual and institutional investors are willing to invest their funds in a field where the return could be substantial both monetarily and morally. The cancer indications possible are numerous not only because of the antigens presented in the different cancers but also due to the ways the drugs can be administered. Future possibilities include more vaccines given as adjuvants to current standards of care of chemotherapy, hormone therapy, radiotherapy and resection. Some of the more aggressive immunotherapies in development could also potentially be given as front-line treatments in which they would be the actual agents to directly attack the cancers initially. These clinicals may also give rise to true cancer vaccines capable of teaching immunity systems in patients with risk factors for developing certain types of cancers to fight cancers at their earliest stages of development, thereby averting a cancer diagnosis in the first place. Simply put, a person's own immunity system taught to fight cancer cells on its own could have the best safety profile and best chance of preventing or fighting cancer. This should become the ultimate and only ethical goal of immunotherapy biotechs or pharmaceuticals desiring to fight one of man's greatest killers. Chemotherapy, radiotherapy, resection, medical devices, growth inhibitors and others currently in the regimen have their place in modern medicine as each has saved or prolonged many lives. Nonetheless, a much less toxic regimen is necessary to attack cancer when it does raise its ugly head either as a standalone or adjuvant, and a preventative regimen at least for those with a propensity to develop cancer due to lifestyle, genetics and other risk factors is likely in the future. Like polio, cancer should be a disease behind us rather than with us. The table below gives us an overview of what is happening and also gives hints at what is possible in the future with each cancer type disappearing and hopefully someday becoming a part of our medical past.
GBM, lung, breast, ovarian, prostate
Breast, glioma, breast, melanoma
Lung, prostate, melanoma, bladder, esophageal, ovarian
Lymphoma/leukemia & solid tumors
Urothelial carcinoma, breast, ovarian, colorectal
Renal, colon, cervical
Breast, lung, colon
Breast, ovarian, colorectal
Endometrial, ovarian, lung, breast, colon, renal
GBM, breast, ovarian, colorectal
GBM, melanoma, head & neck, lung, gastric, ovarian, leukemia
GBM, colon, breast
GBM, head & neck, ovarian, renal
Ovarian, breast, colorectal, prostate, lung, melanoma
Pancreatic, ovarian, mesothelioma
Breast, lung, colon, ovarian, pancreatic
Head & neck, lung, colorectal, GBM