Over the past year, I've written several articles about ImmunoCellular Therapeutics (IMUC) and its lead product, ICT-107, discussing the technology behind the cancer vaccine. On Tuesday, I published an article which presented the company's recent special with Dr. Sanjay Gupta, which puts into perspective the company's progress and its breakthrough in the medical community. However, I decided to break it down further, and in this article I am looking at the disease of glioblastoma multiforme, ICT-107 compared to current treatments, and also what it needs to achieve in order to reach an FDA approval. Later, in part 2 of this article, I will be looking at the manufacturing process of ICT-107 and compare it to current processes as well as expectations, potential revenue and profitability if approved. My goal, is to put this technology and its candidate into perspective, and provide a complete assessment of the biotechnology company, from all aspects.
ImmunoCellular Therapeutics is often compared to Dendreon (DNDN), as both are part of the immunotherapy space, which has been made popular by DNDN due to its first approval with the drug Provenge. Dendreon has had its share of problems with Provenge, as the future is now uncertain, however Dendreon did open the door for other immunotherapy companies that have come behind it and improved upon the technology, such is the case with IMUC.
IMUC has had an exciting year so far; the company was recently added to several Russell Index funds after being listed on the NYSE earlier this year. The company's valuation has mainly been driven by data from its Phase 1 trial in patients with glioblastoma multiforme (GBM).
Some have questioned the results from the Phase 1 trial (i.e. the small patient population, no control group, comparison to historical data, and that it was conducted only at a one hospital), arguing that clinical results from the ongoing Phase 2 trial will not be near as impressive. It would be unrealistic to suggest that results from a larger, randomized, multicenter, ICT-107 trial would be comparable to a Phase 1 trial with only 16 patients. The question that investors should ask is whether or not ICT-107 needs to produce similar results in order to receive an FDA approval.
GBM is the most dangerous and aggressive form of brain cancer. GBM patients typically have short-term life expectancies; few will live to see three years after diagnosis. It is estimated that 11,000 of the 12,000 newly diagnosed GBM patients each year undergo surgical resection followed by radiation and chemotherapy (Temodar) - the current standard of care (SOC). Unfortunately, the cancer inevitably returns within a year after treatment.
In 2005, Merck's (MRK) chemotherapy agent, Temodar, was approved to treat newly diagnosed GBM patients. A randomized, Phase 3 clinical study showed that Temodar only added 2.5 months to the median survival of patients (Stupp et al. NEJM 2005). The chemotherapy agent reduced the size of tumors in over 50% of the patients tested and stabilized the size of the brain tumors in nearly 40% of the patients. However, tumor size increased in 10% of those treated. Despite the fact that Temodar only added 2.5 months to survival and showed no consistency regarding progression of the disease, it still received FDA approval.
Genentech's (RHHBY.PK) Avastin was granted accelerated approval in 2009 for the treatment of GBM patients who have had their cancers come back. The FDA approval was based on results from two open-label, Phase 2 studies (Friedman et al, JCO 2009 and Kreisl et al, JCO 2009). Twenty-six percent of patients who received Avastin saw their tumors, with the effect lasting less than six months. However, neither study showed whether or not Avastin had any improvement on overall survival. The FDA still approved the treatment, even with severe adverse events (Grade 3 or 4) in about half the patients.
Here's the key take-away: the FDA approved both Avastin and Temodar despite little meaningful benefit to patients. So as you can see, the bar has been set pretty low for approval in terms of clinical effect for GBM treatments. The reason is because over the years, very few treatments have been proven to work in treating the disease. It is a vicious disease, and we have very few answers at the moment.
For newly diagnosed GBM patients treated with current SOC, median progression free survival is just 6.9 months, and median overall survival is 14.6 months. In other words, patients typically begin to see tumors recur after seven months, and live just over one year. This makes GBM one of the most deadly forms of cancer. Only 26.5% of newly diagnosed GBM patients live beyond 24 months, and just 16% of patients survive more than three years. So even if a patient is lucky enough to live two years, their chances of living much longer are relatively slim.
ICT-107 Phase 1 Results
Now that you understand the seriousness of GBM, let's incorporate ICT-107's Phase 1 results into the equation. In the company's most recent update, it announced that 8 of the original 16 patients are still alive after four years and that 6 of the 8 are showing no signs of disease progression. In addition, 3 patients have already lived past the five-year mark, and it is possible that some of the other patients could live to see five years as well.
As a person who follows the advancements in oncology, ICT-107's Phase 1 results are simply amazing; there is nothing else in development or on the market with similar results. The bears will once again point to the fact that the Phase 1 study has only 16 patients, but in my opinion, this makes the results even more impressive. The reason is because there are no good outcomes for GBM patients. In order to be diagnosed with the disease, a patient must have a Grade IV tumor, and there are no good Grade IV tumors. Therefore, I look at the clinical results of ICT-107 as a huge positive, with 6 patients still alive after four years, and with only 16 patients tested, which is consistent with standard of care based on 100 patients. Basically, ICT-107 only needed 16 patients to achieve similar results of 100 based on SOC. And IMUC's 16-patient trial achieved what neither Avastin nor Temodar could achieve. Therefore, in the ICT-107 Phase 2 trial, I have no reason to believe that it won't at least have 10 patients from 100 achieve similar results, or show significant improvements over SOC, and if so, it would be considered the most effective vaccine in the market.
IMUC has a lot of margin for error with the ICT-107 Phase 2 trial. There are three factors that suggest that ICT-107 will be successful: 1) GBM is a Stage IV form of brain cancer; therefore all of the original 16 patients were in serious condition; 2) 50% survival over four years far exceeds SOC, which is far less than 10%, meaning if only 20 patients of 100 meet this standard ICT-107 would still be twice as effective as SOC; and 3) all data is superior to current treatments with an average of 16.9 months of median progression free survival compared to just 6.9 months for historical SOC (leaving even more room for error on behalf of IMUC).
The bottom line is that if Temodar increased survival by just 2.5 months and was still approved, then ICT-107 could possibly be approved with similar survival benefit. Patients treated with ICT-107 in the Phase 1 study live 23.8 months longer compared to historical SOC. And what's even more encouraging for IMUC is that Temodar only increased survival by 17% over SOC, while ICT-107 more than 160%. Obviously, there are a lot of factors to determine whether or not a drug is approved, but my reasoning suggests that if a treatment which only increases survival by 2.5 months was approved, then it would be difficult for ICT-107 to not be approved, as we know that it does have some clinical effect on GBM, which will most likely far outweigh both Avastin and Temodar.
How can investors buy IMUC shares after just 16 patients tested with ICT-107 in an uncontrolled, single-center study? The answer, and best defense, is to point to the lack of any truly effective treatment and any no good outcomes for GBM. Sometimes a clinical stage biotechnology company will cherry pick data and use patients with early stages of a disease to make results appear more encouraging. However, with GBM, it doesn't matter if it's 10, 20, 30, or 40 patients, the disease is extremely aggressive, and must surpass three other stages of brain cancer in order to be labeled as GBM, which is the most deadly form of brain cancer, and is a disease where life simply ends. And although ICT-107's Phase 2 results will not likely be as impressive as in Phase 1, investors should remember that it doesn't need to be as effective in order to eventually receive an approval from the FDA. Just look at the data for currently approved drugs, and you will see just how much room for error ICT-107 has in this Phase 2 trial. If results from the Phase 2 study are as good as the Phase 1 trial, I believe the approval of ICT-107 could be much sooner than we anticipate.
The company has now enrolled about 213 patients for the Phase 2 study, at a rate that far exceeds past GBM trials, and we should see interim results in the first quarter of 2013, which could be a major catalyst for the stock if results are even remotely close to the Phase 1 data or if ICT-107 shows a significant improvement over SOC. Only time will tell, but at this point, it's worth watching, and with only a few short months till interim data, it is looking as though patients with this deadly disease may finally have hope of survival, rather than expensive treatments that only prolong the inevitable.