ImmunoCellular Therapeutics, Ltd (IMUC.OB) is a development stage biotech company focused on development and commercialization of innovative cancer therapies. The Company’s lead product candidate, ICT-107, is an autologous (personalized) dendritic cell-based therapeutic cancer vaccine that works by activating a patient’s immune system against specific tumor-associated antigens. IMUC has finished a Phase I trial of ICT-107 in patients with glioblastoma multiforme (GBM), the most common and most aggressive type of primary brain tumor. A Phase II trial is planned to begin soon.
Glioblastoma Multiforme (GBM): the Disease, Treatment Options and the Market Opportunities
Glioblastoma multiforme (GBM), also called glioblastoma, is the most common and most aggressive type of primary brain tumor and accounts for approximately 50% to 60% of all primary brain tumors.
According to National Cancan Institute (NYSE:NCI) data, the peak incidence occurs between the ages of 45 and 70 years. In the United States, the age-adjusted brain tumor incidence rate was 6.5 per 100,000 men and women per year. The age-adjusted death rate was 4.3 per 100,000 men and women per year. It is estimated that 22,020 men and women (11,980 men and 10,040 women) will be diagnosed with and 13,140 men and women will die of cancer of the brain and other nervous system in 2010. Worldwide, approximately 176,000 new cases of brain and other CNS tumors were diagnosed in the year 2000, with an estimated mortality of 128,000.
Glioblastomas are among the most aggressively malignant human neoplasms. The median survival time from the time of diagnosis without any treatment is usually less than I year. Despite multimodality treatment consisting of open craniotomy with surgical resection of as much of the tumor as possible, followed by concurrent or sequential gamma knife radiotherapy, chemoradiotherapy, targeted therapy, and symptomatic care with corticosteroids, median survival is about 14 months. The overall 5-year survival is less than 10% with the standard of care today. Increasing age (> 60 years of age) carries a worse prognostic risk. Death is usually due to cerebral edema or increased intracranial pressure.
It is very difficult to treat glioblastoma due to several complicating factors
- The tumor cells are very resistant to conventional therapies
- The brain is susceptible to damage due to conventional therapy
- The brain has a very limited capacity to repair itself
- Many drugs cannot cross the blood-brain barrier to act on the tumor
Surgery is the first stage of treatment of glioblastoma. It is used to take a section for a pathological diagnosis, to remove some of the symptoms of a large mass pressing against the brain, to remove disease before secondary resistance to radiotherapy and chemotherapy, and to prolong survival.
After surgery, radiotherapy is the mainstay of treatment for glioblastoma. A pivotal clinical trial carried out in the early 1970s showed that GBM patients who received radiation had a median survival more than double those who did not receive radiation therapy. Subsequent clinical research has attempted to build on the backbone of surgery followed by radiation.
Chemotherapy is a third method to treat glioblastoma. Although the addition of chemotherapy to radiation improves survival in many cancer types, this is not the case for glioblastoma. Most studies showed no benefit from the addition of chemotherapy to radiation for glioblastoma patients. Currently, two chemotherapeutic agents (including one targeted therapy) approved by the FDA are frequently used for the treatment of glioblastoma in combination with radiation therapy. They are Temodar (temozolomide) from Merck/Schering Plough for newly diagnosed GBM and Avastin from Roche for recurred GBM.
A large clinical trial of 573 newly diagnosed GBM patients randomized to standard radiation versus radiation plus temozolomide chemotherapy showed that the group receiving temozolomide survived a median of 14.6 months as opposed to 12.1 months for the group receiving radiation alone. This treatment regime is currently considered standard of care for glioblastoma and has a 26% survival at two years.
The US FDA recently approved Avastin (bevacizumab) to treat patients with recurred glioblastoma after standard therapy based on the results of 2 studies that showed Avastin reduced tumor size in some glioblastoma patients. In the first study, the efficacy of Avastin was demonstrated by an objective response rate of 25.9%. Median duration of response was 4.2 months. In the second study, the efficacy of Avastin was supported by an objective response rate of 19.6%. Median duration of response was 3.9 months.
A third chemotherapeutic agent on the market for glioblastoma is Bristol Myers Squibb’s Carmustine injection and Eisai’s Carmustine wafer, which are less frequently used.
Market Opportunities for IMUC’s ICT-107
Clearly, there is an unmet medical need for the treatment of glioblastoma. Relapse of glioblastoma is attributed to the recurrence and persistence of tumor stem cells. Therefore, targeting cancer stem cells (CSCs) may be an ultimate solution to treat glioblastoma more efficaciously with fewer side effects.
IMUC’s lead drug candidate ICT-107 is specifically designed to target glioblastoma stem cells. ICT-107 is similar to Dendreon's (DNDN) newly approved prostate cancer vaccine Provenge. Like Provenge, ICT-107 is made by harvesting dendritic cells from the patient's body. These dendritic cells are then loaded with antigens that are highly specific to CSCs found in GBM tumors, and reintroduce them to the patient’s body to trigger an immune response to destroy these CSCs.
The Company has finished a Phase I trial of ICT-107 for the treatment of glioblastoma which has demonstrated outstanding efficacy data and safety profile.
In total of 16 newly diagnosed GBM patients, two year survival rates were 80% in the drug group compared with the historic median two-year survival rate of 26.5% with standard of care alone. The study's median progression-free (NYSE:PFS) survival of 17.0 months compared especially favorably to the historic median PFS of 6.9 months. Eleven of the 16 patients continue to survive. No serious adverse events have been reported and minor side effects have been limited to fatigue, skin rash and pruritis.
Long-term data from the Phase I clinical trial showed 37.6% patients who received ICT-107 were disease-free after more than two years, with three of these patients (18.8%) remaining disease-free for more than three years. One of these patients remains disease-free after almost four years. No treatment-related serious adverse events have been observed to date.
The above data from ICT-107 are the most compelling so far for the treatment of glioblastoma. The median PFS of 17 months compares favorably with 12.3 months for CDX-110 (Celldex:[[CLDX]]) as reported at SNO meeting last month and 13.6 months for Avastin published earlier this month (Roche:RHHBY). This is encouraging although ICT-107 is at its early stages of development. The Company is initiating a Phase II trial of ICT-107 for the treatment of GBM. The planned Phase II trail will be a double-blinded, placebo-controlled, 2:1 randomized study of ICT-107 in approximately 100 patients with newly diagnosed GBM. The study will be conducted in approximately 15 clinical trial centers in the U.S. and Canada.
The glioblastoma market is a multibillion dollar business. Worldwide sales of Temodar reached $1 billion in 2009 and about $800 million in the first nine months of 2010. If ICT-107 ultimately reaches the market, it will command a huge market share of the GBM market due to its outstanding efficacy data and safety profile in our view. This means a lot to a small biotech company like IMUC even with a few hundred million dollars in sales. With a Phase II trial starting soon, IMUC is one step closer to achieve its long term goal.